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Best Overall Response-associated Signature to Doxorubicin in Soft Tissue Sarcomas: A Transcriptomic Analysis from ANNOUNCE Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-27 Jiangang Liu, David S. Moura, Robin L. Jones, Amit Aggarwal, Ebert J. Philip, Andrew J. Wagner, Jennifer Wright, Javier Martín-Broto, William D. Tap
Purpose: This exploratory analysis evaluated the tumor samples of the patients treated with doxorubicin (with or without olaratumab) in a negative phase-3 ANNOUNCE trial to better understand the complexity of advanced soft tissue sarcomas (STS) and to potentially identify its predictive markers. Experimental Design: RNA sequencing was performed on pretreatment tumor samples (n=273) from the ANNOUNCE
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Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-27 Amy Jamieson, Juliana Sobral de Barros, Dawn R. Cochrane, J. Maxwell Douglas, Sameer Shankar, Branden J. Lynch, Samuel Leung, Spencer Martin, Janine Senz, Amy Lum, Yvette Drew, C. Blake Gilks, David G. Huntsman, Jessica N. McAlpine
Purpose: Shallow whole genome sequencing (sWGS) can detect copy number (CN) aberrations. In high-grade serous ovarian (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers (ECs) to identify additional prognostic stratification and therapeutic opportunities. Experimental design:
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A phase I trial of enzalutamide plus selective glucocorticoid receptor modulator relacorilant in patients with metastatic castration resistant prostate cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-27 Kunal B. Desai, Anthony V. Serritella, Walter M. Stadler, Peter H. O'Donnell, Randy F. Sweis, Russell Z. Szmulewitz
Purpose: Majority of patients with metastatic prostate cancer who receive androgen deprivation therapy and androgen receptor (AR) signaling inhibitors progress. Activation of the glucocorticoid receptor (GR) is associated with ARSI-resistance. This single-arm phase I trial assessed safety and pharmacokinetic feasibility of combined AR antagonist (enzalutamide) and selective GR modulator (relacorilant)
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A Phase 0/1 Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination with Standard Therapy in Recurrent High-Grade Gliomas Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-26 Pankaj B. Desai, Aniruddha Karve, Misam Zawit, Priyanka Arora, Nimita Dave, Joy Awosika, Ningjing Li, Bethany Fuhrman, Mario Medvedovic, Larry Sallans, Ady Kendler, Biplab DasGupta, David Plas, Richard Curry, Mario Zuccarello, Rekha Chaudhary, Soma Sengupta, Trisha M. Wise-Draper
Purpose: High grade gliomas (HGGs) carry a poor prognosis, with glioblastoma accounting for almost 50% of primary brain malignancies in the elderly. Unfortunately, despite the use of multiple treatment modalities, the prognosis remains poor in this population. Our pre-clinical studies suggest that the presence of aromatase expression, encoded by CYP19A1, is significantly upregulated in HGGs. Remarkably
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A Phase I trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-26 Eleftheria Kalogera, Wendy K. Nevala, Heidi D. Finnes, Vera J. Suman, Jill M. Schimke, Carrie A. Strand, Lisa A. Kottschade, Rachel A. Kudgus, Sarah A. Buhrow, Laura R. Becher, Liyi Geng, Gretchen E. Glaser, Megan E. Grudem, Aminah Jatoi, Carolyn M. Klampe, Amanika Kumar, Carrie L. Langstraat, Robert R. McWilliams, Andrea E. Wahner Hendrickson, S. John Weroha, Yiyi Yan, Joel M. Reid, Svetomir N. Markovic
Purpose: AB160 is a 160 nm nano-immunoconjugate consisting of nab-paclitaxel (ABX) nanoparticles non-covalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels of VEGF. Preclinical data showed that AB160 resulted in greater tumor targeting and tumor inhibition compared to sequential treatment with ABX then BEV. Given individual drug activity, we investigated
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Unlocking the Pancreatic Cancer Puzzle: Using Intermediate Cells to Target Treatment Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-26 Erika Y. Faraoni, Florencia McAllister
KRT17-high intermediate cell population with elevated CXCL8 expression informed elevated myeloid infiltration status in tumors and associated with pro-tumorigenic signatures in peripheral granulocytes from pancreatic cancer patients. Further, CXCL8 plasma levels were found to resemble KRT17+/CXCL8+ abundance in tumors, in which higher levels predicted worse patient outcomes.
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Measurement of ctDNA Tumor Fraction Identifies Informative Negative Liquid Biopsy Results and Informs Value of Tissue Confirmation Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-25 Christian D. Rolfo, Russell W. Madison, Lincoln W. Pasquina, Derek W. Brown, Yanmei Huang, Jason D. Hughes, Ryon P. Graf, Geoffrey R. Oxnard, Hatim Husain
Purpose: Liquid biopsy (LBx) for tumor profiling is increasingly used, but concerns remain regarding negative results. A lack of results may truly reflect tumor genomics, or it may be a false negative that would be clarified by tissue testing. A method of distinguishing between these scenarios could help clarify when follow-on tissue testing is valuable. Experimental Design: Here we evaluate circulating
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A Prospective Double-Blinded Comparison of Reflectance Confocal Microscopy with Conventional Histopathology for In Vivo Assessment in Oral Cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-25 Daniella K. Zanoni, Paula Demétrio De Souza França, Cristina Valero, Gary Peterson, Marco Ardigo, Ronald Ghossein, Stephen W. Dusza, Danielli Matsuura, Daniel W. Scholfield, Dauren Adilbay, Pablo H. Montero, Jocelyn Migliacci, Naga Vara Kishore Pillarsetty, Kivanc Kose, Ian Ganly, Milind Rajadhyaksha, Snehal G. Patel
Purpose: We investigated reflectance confocal microscopy (RCM) as a possible non-invasive approach for the diagnosis of cancer and real-time assessment of surgical margins. Patients and methods: In a phase I study on 20 patients, we established the RCM imaging morphological features that distinguish OSCC from normal tissue with a newly developed intra-oral RCM probe. Our subsequent phase II prospective
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Upfront neck dissection for treatment selection and improvement in quality of life as a novel treatment paradigm for deintensification in HPV+ OPSCC Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-22 Paul L. Swiecicki, Emily Bellile, Aleksandar F. Dragovic, Jonathan McHugh, Aaron Udager, Michelle Lynn. Mierzwa, Jennifer Shah, Molly Heft Neal, Andrew Rosko, Kelly M. Malloy, Keith Casper, Steven Bennett. Chinn, Andrew G. Shuman, Chaz Stucken, Douglas B. Chepeha, Gregory T. Wolf, Carol Rossier. Bradford, Avraham Eisbruch, Mark E.P. Prince, Francis P. Worden, Matthew E. Spector
Purpose: Locoregionally advanced HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has excellent cure rates, although current treatment regimens are accompanied by acute and long-term toxicities. We designed a phase II de-escalation trial for patients with HPV+OPSCC to evaluate the feasibility of an upfront neck dissection to individualize definitive treatment selection to improve quality of life
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Improvements in Posttransplant Outcomes Over Two Decades in Older Patients with Acute Myeloid Leukemia in the EBMT ALWP Study Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-22 Ali Bazarbachi, Myriam Labopin, Nour Moukalled, Nicolaus Kröger, Christina Rautenberg, Johannes Schetelig, Jürgen Finke, Igor Wolfgang Blau, Didier Blaise, Matthias Stelljes, Matthias Eder, Uwe Platzbecker, Peter Dreger, Wolfgang Bethge, Johanna Tischer, David Burns, Henrik Sengeloev, Eolia Brissot, Sebastian Giebel, Arnon Nagler, Fabio Ciceri, Mohamad Mohty
Purpose: Acute myeloid leukemia (AML) is a disease of older patients. Progress in allogeneic hematopoietic cell transplantation (allo-HCT) allowed the delivery of allo-HCT to older patients. We assessed changes over time in transplant characteristics and outcomes in patients with AML ages 65 years and above. Patients and Methods: We identified 7,215 patients with AML (median age 68 years, range 65–80)
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Memory/active T cell activation is associated with immunotherapeutic response in fumarate hydratase-deficient renal cell carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-21 Junru Chen, Xu Hu, Junjie Zhao, Xiaoxue Yin, Linmao Zheng, Jingjing Guo, Jianhui Chen, Yongquan Wang, Xinan Sheng, Haiying Dong, Xiaodong Liu, Xingming Zhang, Jiayu Liang, Haolin Liu, Jin Yao, Jiyan Liu, Yali Shen, Zhibin Chen, Zhengyu He, Yaodong Wang, Ni Chen, Ling Nie, Mengni Zhang, Xiuyi Pan, Yuntian Chen, Haoyang Liu, Yaowen Zhang, Yanfeng Tang, Sha Zhu, Jinge Zhao, Jindong Dai, Zilin Wang, Yuhao
Purpose: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. Experimental Design: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA sequencing
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A Signal-finding Study of Abemaciclib in Heavily Pretreated Patients with Metastatic Castration-Resistant Prostate Cancer: Results from CYCLONE 1 Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-21 Neeraj Agarwal, Daniel Castellano, Teresa Alonso-Gordoa, Jose Angel. Arranz Arija, Emeline Colomba, Gwenaelle Gravis, Loic Mourey, Stephane Oudard, Aude Fléchon, Macarena Gonzalez, Pablo M. Maroto, Michael T. Schweizer, Enrique Gallardo, Erica Johnston, Arjun Balar, Nadine Haddad, Adams K. Appiah, Karim Nacerddine, Josep M. Piulats
Background: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors radically changed the treatment paradigm for breast cancer. Similar to estrogen receptor in breast cancer, androgen receptor signaling activates cyclin D-CDK4/6, driving proliferation and resistance to hormonal manipulation in prostate cancer. This study was designed to detect signals of clinical activity for abemaciclib in treatment-refractory
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Phase I trial of viral vector based personalized vaccination elicits robust neoantigen specific antitumor T cell responses Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-20 Anna Morena. D'Alise, Guido Leoni, Gabriella Cotugno, Loredana Siani, Rosa Vitale, Valentino Ruzza, Irene Garzia, Laura Antonucci, Elisa Micarelli, Veronica Venafra, Sven Gogov, Alessia Capone, Sarah Runswick, Juan Martin-Liberal, Emiliano Calvo, Victor Moreno, Stefan N. Symeonides, Elisa Scarselli, Oliver Bechter
Purpose: Personalized vaccines targeting multiple neoantigens (nAgs) are a promising strategy for eliciting a diversified antitumor T cell response to overcome tumor heterogeneity. NOUS-PEV is a vector based personalized vaccine, expressing 60 nAgs and consists of priming with a non-human Great Ape Adenoviral vector (GAd20) followed by boosts with Modified Vaccinia Ankara (MVA). Here, we report data
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Cell Context is the third axis of synergy for the combination of ATR inhibition and cisplatin in Ewing sarcoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-20 Jennifer Jess, Kathleen M. Sorensen, Elissa A. Boguslawski, Matthew C. Stout, Zachary B. Madaj, Benjamin P. Caiello, Monica Pomaville, Elizabeth R. Wilson, Seneca S. Kinn-Gurzo, Curtis C. Parker, Sridhar M. Veluvolu, Taylor V. Brysgel, Rebecca Kaufman, Susan M. Kitchen-Goosen, Jenna M. Gedminas, Patrick J. Grohar
Purpose: The importance of cellular context to the synergy of DNA Damage Response (DDR) targeted agents is important for tumors with mutations in DDR pathways, but less well-established for tumors driven by oncogenic transcription factors. In this study, we exploit the widespread transcriptional dysregulation of the EWS-FLI1 transcription factor to identify an effective DDR targeted combination therapy
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Molecular and Clinical Determinants of Acquired Resistance and Treatment Duration for Targeted Therapies in Colorectal Cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-19 Emily Harrold, Fergus Keane, Henry Walch, Joanne F. Chou, Jenna Sinopoli, Silvia Palladino, Duaa H. Al-Rawi, Kalyani Chadalavada, Paolo Manca, Sree Chalasani, Jessica Yang, Andrea Cercek, Jinru Shia, Marinela Capanu, Samuel F. Bakhoum, Nikolaus Schultz, Walid K. Chatila, Rona Yaeger
Purpose: Targeted therapies have improved outcomes for patients with metastatic colorectal cancer, but their impact is limited by rapid emergence of resistance. We hypothesized that an understanding of the underlying genetic mechanisms and intrinsic tumor features that mediate resistance to therapy will guide new therapeutic strategies and ultimately allow the prevention of resistance. Experimental
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Xevinapant combined with pembrolizumab in patients with advanced, pretreated colorectal and pancreatic cancer: results of the phase 1b/2 CATRIPCA trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-19 Allison Voisin, Catherine Terret, Camille Schiffler, Anne-Sophie Bidaux, Hélène Vanacker, Marlène Perrin-Niquet, Maud Barbery, Armelle Vinceneux, Lauriane Eberst, Pierre Stephan, Gwenaele Garin, Dany Spaggiari, David Pérol, Yenkel Grinberg-Bleyer, Philippe A. Cassier
Purpose: Xevinapant is an orally available inhibitor of apoptosis proteins (IAP) inhibitor. Preclinical data suggest that IAP antagonism may synergize with immune checkpoint blockers (ICB) by modulating the NF-KB pathway in immune cells. Patients and Methods: Adult patients (pts) with non MSI-H advanced/metastatic PDAC or CRC were enrolled in this phase 1b/2 and received pembrolizumab 200mg q3w, IV
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Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-15 Josephine K. Dermawan, Sarah Chiang, Samuel Singer, Bhumika Jadeja, Martee L. Hensley, William D. Tap, Sujana Movva, Robert G. Maki, Cristina R. Antonescu
Purpose: Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous tumors. Despite genomic studies, current LMS risk stratification is not informed by molecular alterations. We propose a clinically applicable genomic risk stratification model. Experimental Design: We performed comprehensive genomic profiling in a cohort of 195 soft tissue LMS (STLMS), 151 primary at presentation, and a control
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Rintatolimod in Advanced Pancreatic Cancer enhances Anti-Tumor Immunity through Dendritic Cell-Mediated T Cell Responses Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-15 Casper W.F. van Eijck, Hassana el Haddaoui, Songul Kucukcelebi, Disha Vadgama, Amine Fellah, Dana A.M. Mustafa, Joachim G.J.V. Aerts, Casper H.J. van Eijck, Marcella Willemsen
Purpose: Amid the need for new approaches to improve survival in pancreatic ductal adenocarcinoma (PDAC), immune-based therapies have garnered interest. Rintatolimod, a toll-like receptor 3 (TLR-3) agonist, is a potential candidate due to its dual impact on restraining PDAC cell functions and boosting the anti-tumor immune response. This study investigates the effect of TLR-3 activation through rintatolimod
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Integrative molecular analyses of the MD Anderson prostate cancer patient-derived xenograft (MDA PCa PDX) series Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-15 Nicolas Anselmino, Estefania Labanca, Peter D.A. Shepherd, Jiabin Dong, Jun Yang, Xiaofei Song, Subhiksha Nandakumar, Ritika Kundra, Cindy J. Lee, Nikolaus Schultz, Jianhua Zhang, John C. Araujo, Ana M. Aparicio, Sumit K. Subudhi, Paul G. Corn, Louis L. Pisters, John F. Ward, John W. Davis, Elba S. Vazquez, Geraldine Gueron, Christopher J. Logothetis, Andrew Futreal, Patricia Troncoso, Yu Chen, Nora
Purpose: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer (PCa) models. This initiative builds on the rich MD Anderson (MDA) PCa patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated
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First-Line Anlotinib Treatment for Soft Tissue Sarcoma in Chemotherapy-Ineligible Patients: An Open-label, Single-arm, Phase 2 Clinical Trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-14 Tao Li, Ying Dong, Yongzhong Wei, Shoufeng Wang, Yunxia Liu, Jia Chen, Wenhua Xiong, Nong Lin, Xin Huang, Meng Liu, Xiaobo Yan, Zhaoming Ye, Binghao Li
Purpose: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma (LA/M STS) is chemotherapy based on anthracyclines, but patient tolerance of chemotherapy is limited. The present trial (NCT03792542) investigated the use of anlotinib as first-line treatment for patients with advanced STS, in particular liposarcoma (LPS). Patients and Methods: Eligible patients
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Translational frontiers and clinical opportunities of immunologically-fitted radiotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-13 Daphné Morel, Charlotte Robert, Nikos Paragios, Vincent Grégoire, Eric Deutsch
Ionising radiations can have a wide range of impacts on tumour-immune interactions, which are being studied with the greatest interest and at an accelerating pace by the medical community. Despite its undeniable immunostimulatory potential, it clearly appears that radiotherapy as it is prescribed and delivered nowadays often alters the host’s immunity towards a suboptimal state. This may impair the
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Infiltrative vessel co-optive growth pattern induced by IQGAP3 overexpression promotes microvascular invasion in hepatocellular carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-12 Miaoling Tang, Shuxia Zhang, Meisongzhu Yang, Rongni Feng, Jinbin Lin, Xiaohong Chen, Yingru Xu, Ruyuan Yu, Xinyi Liao, Ziwen Li, Xincheng Li, Man Li, Qiliang Zhang, Suwen Chen, Wanying Qian, Yuanji Liu, Libing Song, Jun Li
Purpose: Microvascular invasion (MVI) is a major unfavorable prognostic factor for intrahepatic metastasis and postoperative recurrence of hepatocellular carcinoma (HCC). However, the intervention and preoperative prediction for MVI remain clinical challenges due to the absent precise mechanism and molecular marker(s). Herein, we aimed to investigate the mechanisms underlying vascular invasion that
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Polo-like kinase 1 inhibition in KRAS-mutated metastatic colorectal cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-12 Justin Stebbing, Andrea J. Bullock
Inhibition of Polo-like kinase 1 (Plk1) is a promising new target and therapeutic strategy in metastatic colorectal cancer, especially those with KRAS mutations. New data support further development of onvansertib, and highlights the role of circulating tumor DNA in phase 1 clinical trials.
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Cell-free DNA concentration as a biomarker of response and recurrence in HER2-negative breast cancer receiving neoadjuvant chemotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-12 Mark Jesus M. Magbanua, Ziad Ahmed, Rosalyn W. Sayaman, Lamorna Brown Swigart, Gillian L. Hirst, Christina Yau, Denise M. Wolf, Wen Li, Amy L. Delson, Jane Perlmutter, Paula Pohlmann, W. Fraser. Symmans, Douglas Yee, Nola M. Hylton, Laura J. Esserman, Angela M. DeMichele, Hope S. Rugo, Laura J. van 't Veer
Purpose: We previously demonstrated the clinical significance of circulating tumor DNA (ctDNA) in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC). Here, we compared its predictive and prognostic value with cell-free DNA (cfDNA) concentration measured in the same samples from the same patients. Experimental Design: 145 hormone receptor (HR)-positive/HER2-negative and
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Tumor-infiltrating lymphocytes refine outcomes in triple-negative breast cancer treated with anthracycline-free neoadjuvant chemotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-11 Miguel Martín, Rachel Yoder, Roberto Salgado, Maria del Monte-Millán, Enrique L. Alvarez, Isabel Echavarría, Joshua M. Staley, Anne P. O'Dea, Lauren E. Nye, Shane R. Stecklein, Coralia Bueno Muiño, Yolanda Jerez-Gilarranz, María Cebollero, Oscar Bueno, Jose Ángel. Garcia-Saenz, Fernando Moreno, Uriel Bohn, Henry Gomez, Tatiana Massarrah, Qamar J. Khan, Andrew K. Godwin, Sara López-Tarruella, Priyanka
Background: Stromal tumor-infiltrating lymphocytes (sTILs) are associated with pathologic complete response (pCR) and long-term outcomes for triple-negative breast cancer (TNBC) in setting of anthracycline-based chemotherapy. Impact of sTILs on refining outcomes beyond prognostic information provided by pCR in anthracycline-free neoadjuvant chemotherapy (NAC) is not known. Patients & Methods: This
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Biomarkers of efficacy and safety of the academic BCMA-CART ARI0002h for the treatment of refractory multiple myeloma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-11 Aina Oliver-Caldés, Marta Español-Rego, Aintzane Zabaleta, Veronica Gonzalez-Calle, Sergio Navarro-Velázquez, Susana Inoges, Ascensión López-Díaz de Cerio, Valentin Cabañas, Nieves López-Muñoz, Paula Rodriguez-Otero, Juan Luis. Reguera-Ortega, David F. Moreno, Núria Martínez-Cibrian, Lucía López-Corral, Lorena Pérez-Amill, Beatriz Martin-Antonio, Laura Rosinol, Joan Cid, Natalia Tovar, Joaquin Saez-Peñataro
Background: BCMA-CARTs improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to
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Phase 1/2 study of combined BCL-xL and MEK inhibition with navitoclax and trametinib in KRAS or NRAS mutant advanced solid tumors Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-08 Ryan B. Corcoran, Khanh T. Do, Jeong E. Kim, James M. Cleary, Aparna R. Parikh, Oladapo O. Yeku, Niya Xiong, Colin D. Weekes, Jennifer Veneris, Leanne G. Ahronian, Gianluca Mauri, Jun Tian, Bryanna L. Norden, Alexa G. Michel, Emily E. Van Seventer, Giulia Siravegna, Kyle Camphausen, Gary Chi, Isobel J. Fetter, Joan S. Brugge, Helen X. Chen, Naoko Takebe, Richard T. Penson, Dejan Juric, Keith T. Flaherty
Purpose: MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi. Patients and Methods: We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts
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A phase II open-label randomized clinical trial of preoperative durvalumab or durvalumab plus tremelimumab in resectable head and neck squamous cell carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-08 Chang Gon Kim, Min Hee Hong, Dahee Kim, Brian Hyohyoung. Lee, Hyunwook Kim, Chan-Young Ock, Geoffrey Kelly, Yoon Ji Bang, Gamin Kim, Jung Eun Lee, Chaeyeon Kim, Se-Heon Kim, Hyun Jun Hong, Young Min Park, Nam Suk Sim, Heejung Park, Jin Woo Park, Chang Geol Lee, Kyung Hwan Kim, Goeun Park, Inkyung Jung, Dawoon Han, Jong Hoon Kim, Junha Cha, Insuk Lee, Mingu Kang, Heon Song, Chiyoon Oum, Seulki Kim,
Purpose: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Patients and Methods: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiation
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Therapeutic Targeting of TIM-4-L With Engineered T Cells for Acute Myeloid Leukemia Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-07 Brandon Cieniewicz, Edson Oliveira, Mike Saxton, Damoun Torabi, Ankit Bhatta, Phanidhar Kukutla, Alexander Arballo, Zhuo Yang, Bi Yu, Maria Fate, Hongxiu Ning, Lawrence Corey, Abhishek Maiti, Daniel Corey
Purpose: Disruption of lipid bilayer asymmetry is a common feature observed in cancer cells and offers novel routes for therapeutic targeting. We utilized the natural immune receptor TIM-4 to interrogate for loss of plasma membrane phospholipid polarity in primary acute myelogenous leukemia (AML) samples and evaluated the anti-leukemic activity of TIM-4-L-directed T cell therapy in preclinical AML
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Targeting CCL2/CCR2 signaling overcomes MEK inhibitor resistance in Acute Myeloid Leukemia Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-07 Rucha V. Modak, Katia G. de Oliveira Rebola, John McClatchy, Mona Mohammadhosseini, Alisa Damnernsawad, Stephen E. Kurtz, Christopher A. Eide, Guanming Wu, Ted Laderas, Tamilla Nechiporuk, Marina A. Gritsenko, Joshua R. Hansen, Chelsea Hutchinson, Sara J.C. Gosline, Paul Piehowski, Daniel Bottomly, Nicholas Short, Karin Rodland, Shannon K. McWeeney, Jeffrey W. Tyner, Anupriya Agarwal
Purpose: Emerging evidence underscores the critical role of extrinsic factors within the microenvironment in protecting leukemia cells from therapeutic interventions, driving disease progression, and promoting drug resistance in acute myeloid leukemia (AML). This emphasizes the need for the identification of targeted therapies that inhibit intrinsic and extrinsic signaling to overcome drug resistance
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Plasma Proteomic Signature Predicts Myeloid Neoplasm Risk Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-06 Duc Tran, J. Scott. Beeler, Jie Liu, Brian Wiley, Irenaeus C.C. Chan, Zilan Xin, Michael H. Kramer, Armel L. Batchi-Bouyou, Xiaoyu Zong, Matthew J. Walter, Giulia E. M. Petrone, Sarantis Chlamydas, Francesca Ferraro, Stephen T. Oh, Daniel C. Link, Ben Busby, Yin Cao, Kelly L. Bolton
Purpose: Clonal hematopoiesis (CH) is thought to be the origin of myeloid neoplasms (MN). Yet our understanding of the mechanisms driving CH progression to MN and clinical risk prediction of MN remains limited. The human proteome reflects complex interactions between genetic and epigenetic regulation of biological systems. We hypothesized that the plasma proteome might predict MN risk and inform our
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Response rate and molecular correlates to encorafenib and binimetinib in BRAF-V600E mutant high-grade glioma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-06 Karisa C. Schreck, Roy E. Strowd, Louis B. Nabors, Benjamin M. Ellingson, Michael Chang, Sze K. Tan, Zied Abdullaev, Rust Turakulov, Kenneth Aldape, Neeraja Danda, Serena Desideri, Joy Fisher, Michaella Iacoboni, Trisha Surakus, Michelle A. Rudek, Chetan Bettegowda, Stuart A. Grossman, Xiaobu Ye
Purpose: While fewer than 5% of high-grade gliomas (HGG) are BRAF-V600E mutated, these tumors are notable as BRAF-targeted therapy shows efficacy for some populations. The purpose of this study was to evaluate response to the combination of encorafenib with binimetinib in adults with recurrent BRAF-V600 mutated HGG. Patients and methods: In this phase 2, open-label, Adult Brain Tumor Consortium (ABTC)
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A Single Arm Phase 2 Trial of Trametinib in Patients With Locally Advanced or Metastatic Epithelioid Hemangioendothelioma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-06 Scott M. Schuetze, Karla V. Ballman, Rachel Heise, Kristen N. Ganjoo, Elizabeth J. Davis, Suzanne George, Melissa A. Burgess, Edwin Choy, Dale R. Shepard, Gabriel Tinoco, Angela Hirbe, Ciara M. Kelly, Steven Attia, Hari A. Deshpande, Gary K. Schwartz, Brittany L. Siontis, Richard F. Riedel, Margaret von Mehren, Erin Kozlowski, Helen X. Chen, Caroline Astbury, Brian P. Rubin
Purpose: Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with pathogenic TAZ-CAMTA1 operating as an oncogenic driver through activation of MAPK pathway. Trametinib is an inhibitor of MEK, a critical kinase in the MAPK pathway. We sought to evaluate the effect of trametinib in patients with EHE. Patients and Methods: A phase 2 trial of trametinib was conducted in patients with locally
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Mesenchymal Stem/Stromal Cell Therapy for Radiation-Induced Xerostomia in Previous Head and Neck Cancer Patients: A Phase 2 Randomised, Placebo-Controlled Trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-05 Kathrine Jakobsen, Amanda-Louise Fenger. Carlander, Tobias Todsen, Jacob Melchiors, Natasja Paaske, Anne Kathrine. Østergaard Madsen, Simone Kloch Bendtsen, Christine Mordhorst, Helene Stampe, Jens Kastrup, Annette Ekblond, Mandana Haack-Sørensen, Mohammad Farhadi, Christian Maare, Jeppe Friborg, Charlotte Duch Lynggaard, Anne Werner Hauge, Robin Christensen, Christian Grønhøj, Christian von Buchwald
Purpose: No effective treatment exists for radiation-induced xerostomia. The objective of this study was to compare the effect of adipose-derived mesenchymal stem/stromal cell (ASC) injection, relative to placebo, on salivary gland function in patients with radiation-induced xerostomia. Patient and Methods: In this single-centre, double-blind, placebo-controlled trial, patients with hyposalivation
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FDA Approval Summary: Enfortumab Vedotin Plus Pembrolizumab for Cisplatin-Ineligible Locally Advanced or Metastatic Urothelial Carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-05 William F. Maguire, Daniel Lee, Chana Weinstock, Xin Gao, Catharine C. Bulik, Sundeep Agrawal, Elaine Chang, Salaheldin S. Hamed, Erik W. Bloomquist, Shenghui Tang, Richard Pazdur, Paul G. Kluetz, Laleh Amiri-Kordestani, Daniel L. Suzman
On April 3, 2023, the FDA granted accelerated approval to enfortumab vedotin-ejfv (EV) plus pembrolizumab for treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. Substantial evidence of effectiveness was obtained from EV-103/KEYNOTE-869 (NCT03288545), a multi-cohort study. Across cohorts, a total of 121 patients received
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The irreversible FGFR inhibitor KIN-3248 overcomes FGFR2 kinase domain mutations. Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-04 Eranga R. Balasooriya, Qibiao Wu, Haley Ellis, Yuanli Zhen, Bryanna L. Norden, Ryan B. Corcoran, Adithi Mohan, Eric Martin, Aleksandra Franovic, John Tyhonas, Matthew Lardy, Kathryn B. Grandinetti, Robert Pelham, Liliana Soroceanu, Vanessa S. Silveira, Nabeel Bardeesy
Purpose: FGFR2 and FGFR3 show oncogenic activation in many cancer types, often through chromosomal fusion or extracellular domain mutation. FGFR2 and FGFR3 alterations are most prevalent in intrahepatic cholangiocarcinoma (ICC) and bladder cancers, respectively, and multiple selective reversible and covalent pan-FGFR tyrosine kinase inhibitors (TKIs) have been approved in these contexts. However, resistance
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A Pre-Leukemic DNA Methylation Signature in Healthy Individuals at Higher Risk for Developing Myeloid Malignancy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-04 Zhentang Lao, Ling-Wen Ding, Qiao-Yang Sun, Li Jia, Benedict Yan, Alvin Yu-Jin. Ng, Sharah Mae. Capinpin, Renwei Wang, Li Ying, Wee Joo Chng, H. Phillip Koeffler, Woon-Puay Koh, Jian-Min Yuan, Henry Yang, Yeow Tee Goh, Nicholas Grigoropoulos
Purpose: DNA methylation alterations are widespread in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), some of which appear to have evolved independently of somatic mutations in epigenetic regulators. While the presence of somatic mutations in peripheral blood can predict the risk of development of AML and MDS, its accuracy remains unsatisfactory. Experimental Design: We performed
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Trastuzumab and Pertuzumab in Patients with Non-Breast/Gastroesophageal HER2-Amplified Tumors: Results from the NCI–MATCH ECOG–ACRIN Trial (EAY131) Subprotocol J Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-04 Roisin M. Connolly, Victoria Wang, David M. Hyman, Petros Grivas, Edith P. Mitchell, John J. Wright, Elad Sharon, Robert J. Gray, Lisa M. McShane, Larry V. Rubinstein, David R. Patton, P. Mickey Williams, Stanley R. Hamilton, Jue Wang, Kari B. Wisinski, James V. Tricoli, Barbara A. Conley, Lyndsay N. Harris, Carlos L. Arteaga, Peter J. O'Dwyer, Alice P. Chen, Keith T. Flaherty
Purpose: NCI–MATCH assigned patients with advanced cancer and progression on prior treatment, based on genomic alterations in pretreatment tumor tissue. Arm J (EAY131-J) evaluated the combination of trastuzumab/pertuzumab (HP) across HER2-amplified tumors. Patients and Methods: Eligible patients had high levels of HER2 amplification [copy number (CN) ≥7] detected by central next-generation sequencing
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Radiotherapy Enhances Metastasis Through Immune Suppression by inducing PD-L1 and MDSC in distal sites Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-01 Yuzhu Hou, Kaiting Yang, Liangliang Wang, Jiaai Wang, Xiaona Huang, Andras Piffko, Sean Z. Luo, Xinshuang Yu, Enyu Rao, Carlos Martinez, Jason Bugno, Matthias Mack, Everett E. Vokes, Sean P. Pitroda, Steven J. Chmura, Ralph R. Weichselbaum, Hua Laura. Liang
Purpose: Radiotherapy (RT) is a widely employed anti-cancer treatment. Emerging evidence suggests that RT can elicit both tumor-inhibiting and tumor-promoting immune effects. This study is to investigate immune suppressive factors of radiotherapy. Experimental Design: We used a heterologous two-tumor model in which adaptive concomitant immunity was eliminated. Results: Through analysis of PD-L1 expression
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Improved risk stratification scheme for mismatch repair proficient stage II colorectal cancers using the digital pathology biomarker QuantCRC Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-29 Christina Wu, Reetesh K. Pai, Heidi Kosiorek, Imon Banerjee, Ashlyn Pfeiffer, Catherine E. Hagen, Christopher P. Hartley, Rondell P. Graham, Mohamad B. Sonbol, Tanios Bekaii-Saab, Hao Xie, Frank A. Sinicrope, Bhavik Patel, Thomas Westerling-Bui, Sameer Shivji, James Conner, Carol Swallow, Paul Savage, David P. Cyr, Richard Kirsch, Rish K. Pai
Purpose: There is a need to improve current risk stratification of stage II colorectal cancer (CRC) to better inform risk of recurrence and guide adjuvant chemotherapy. We sought to examine whether integration of QuantCRC, a digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines
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Ataxia-Telangiectasia Mutated (ATM) loss of function displays variant and tissue-specific differences across tumor types Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-28 Patrick G. Pilie, Virginia Giuliani, Wei-Lien Wang, Daniel J. McGrail, Christopher A. Bristow, Natalie Y.L. Ngoi, Keith Kyewalabye, Khalida M. Wani, Hung Le, Erick Campbell, Nora S. Sánchez, Dong Yang, Jinesh S. Gheeya, Rohit Vivek. Goswamy, Vijaykumar Holla, Kenna Rael. Shaw, Funda Meric-Bernstam, Chiu-Yi Liu, XiaoYan Ma, Ningping Feng, Annette A. Machado, Jennifer P. Bardenhagen, Christopher P. Vellano
Purpose: Mutations in the ATM gene are common in multiple cancers, but clinical studies of therapies targeting ATM aberrant cancers have yielded mixed results. Refinement of ATM loss of function (LOF) as a predictive biomarker of response is urgently needed. Experimental Design: We present the first disclosure and preclinical development of a novel, selective ATR inhibitor, ART0380, and test its antitumor
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Molecular profiling and the impact of treatment on outcomes in adenoid cystic carcinoma (ACC) type-I and II Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-28 Glenn J. Hanna, Punita Grover, Andrew Elliott, Julie McGrath, Joanne Xiu, Ammar Sukari, Jennifer M. Johnson, Trisha Wise-Draper
Background: Adenoid cystic carcinoma (ACC) is an uncommon salivary gland cancer with no approved therapies available to treat advanced, incurable disease. Recent molecular profiling efforts have identified two important subtypes: the more aggressive ACC-I is characterized by Notch pathway alterations and MYC amplification while ACC-II demonstrates a more indolent phenotype and TP63 overexpression.
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All that is small is not a small cell carcinoma: Thoracic SMARCA4 undifferentiated tumors masquerading as SCLC Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-28 Natasha Rekhtman
Small cell lung carcinoma (SCLC) cell lines have been widely utilized as a preclinical model of this highly aggressive disease. However, since their creation decades ago, novel tumor entities have been defined that may clinicopathologically mimic SCLC, which notably includes thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Multi-omic reassessment of the presumed SCLC cell lines with
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A Pooled Analysis of Treatment-Free Survival in Advanced Renal Cell Carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-28 Elaine Chang, Jiaxi Zhou, Chi Song, Haley Gittleman, Laura Fernandes, Chana Weinstock, Michael B. Atkins, Sundeep Agrawal, Rajeshwari Sridhara, Nicole Gormley, Shenghui Tang, Daniel L. Suzman, Laleh Amiri-Kordestani, Paul G. Kluetz, Richard Pazdur, Brian I. Rini, David F. McDermott, Meredith M. Regan
Purpose: A clinically meaningful attribute of some immune-oncology (IO) regimens is potential durable clinical benefit during a treatment-free interval. We characterize treatment-free survival (TFS) with and without ongoing toxicity in trials of frontline IO-VEGF tyrosine kinase inhibitor (TKI) combinations in patients with advanced renal cell carcinoma (aRCC). Patients and Methods: Individual patient
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Adult-onset cancer predisposition syndromes in children and adolescents – to test or not to test? Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-27 Christian P. Kratz, Philip J. Lupo, Kristin Zelley, Jaclyn Schienda, Kim E. Nichols, Douglas R. Stewart, David Malkin, Garrett M. Brodeur, Kara Maxwell, Sharon E. Plon, Michael F. Walsh
With the increasing use of comprehensive germline genetic testing of children and adolescents with cancer, it has become evident that pathogenic variants (PVs) in adult-onset cancer predisposition genes (aoCPGs) underlying adult-onset cancer predisposition syndromes (aoCPS) such as Lynch syndrome or hereditary breast and ovarian cancer are enriched and reported in one to two percent of children and
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First-in-Human Study of the Ataxia Telangiectasia and Rad3-related (ATR) Inhibitor Tuvusertib (M1774) as Monotherapy in Patients with Solid Tumors Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-26 Timothy A. Yap, Anthony W. Tolcher, Ruth Plummer, Jatinder Kaur. Mukker, Marta Enderlin, Christine Hicking, Thomas Grombacher, Giuseppe Locatelli, Zoltan Szucs, Ioannis Gounaris, Johann S. de Bono
Purpose: Tuvusertib (M1774) is a potent, selective, orally administered ATR protein kinase inhibitor. This first-in-human study (NCT04170153) evaluated safety, tolerability, maximum tolerated dose (MTD), recommended dose for expansion (RDE), pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of tuvusertib monotherapy. Patients and Methods: Ascending tuvusertib doses were evaluated
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Cadonilimab combined with chemotherapy with or without bevacizumab as first-line treatment in recurrent or metastatic cervical cancer (COMPASSION-13): a phase 2 study Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-26 Hanmei Lou, Hongbing Cai, Xin Huang, Guiling Li, Li Wang, Fei Liu, Wenjing Qin, Ting Liu, Wei Liu, Zhongmin Maxwell. Wang, Baiyong Li, Yu Xia, Jing Wang
Purpose: Immune checkpoint inhibitors (ICIs) have been potential treatment option for patients with cervical cancer in several clinical studies. We investigated the safety and efficacy of cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, plus standard therapy for the first-line treatment of R/M CC. Patients and Methods: Eligible patients were assigned to 3 cohorts: cohort A-15 (cadonilimab
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Improved Innate Immune Function in Patients with Chronic Lymphocytic Leukemia Treated with Targeted Therapy in Clinical Trials Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-23 Rebecca Svanberg Teglgaard, Hanne Vibeke. Marquart, Hans Jakob. Hartling, Jakob Thaning. Bay, Caspar da Cunha-Bang, Christian Brieghel, Tereza Faitová, Lisbeth Enggaard, Arnon P. Kater, Mark-David Levin, Sabina Kersting, Sisse Rye. Ostrowski, Carsten U. Niemann
Purpose: CLL patients have increased risk of severe infections. While adaptive immune dysfunction is well-described, clinical tools for identifying patients at risk are lacking, warranting investigation of additional immune components. In contrast to chemotherapy, targeted agents could spare or even improve innate immune function. Therefore, we investigated innate immune phenotypes and function in
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Belzutifan for von Hippel-Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-23 Tobias Else, Eric Jonasch, Othon lliopoulos, Kathryn E. Beckermann, Vivek Narayan, Benjamin L. Maughan, Stephane Oudard, Jodi K. Maranchie, Ane B. Iversen, Cynthia Muller. Goldberg, Wei Fu, Rodolfo F. Perini, Yanfang Liu, W. Marston Linehan, Ramaprasad Srinivasan
Purpose: Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel-Lindau (VHL) disease–associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease-associated pancreatic lesions (pancreatic neuroendocrine tumors [pNETs] and serous
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Mesothelin CAR T-cells secreting anti-FAP/anti-CD3 molecules efficiently target pancreatic adenocarcinoma and its stroma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-23 Marc Wehrli, Samantha Guinn, Filippo Birocchi, Adam Kuo, Yi Sun, Rebecca C. Larson, Antonio J. Almazan, Irene Scarfò, Amanda A. Bouffard, Stefanie R. Bailey, Praju Vikas. Anekal, Paula Montero Lopis, Linda T. Nieman, Yuhui Song, Katherine H. Xu, Trisha R. Berger, Michael C. Kann, Mark B. Leick, Harrison Silva, Diego Salas-Benito, Tamina Kienka, Korneel Grauwet, Todd D. Armstrong, Rui Zhang, Qingfeng
Purpose: Targeting solid tumors with CAR T-cells remains challenging due to heterogenous target antigen expression, antigen escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated by cancer-associated fibroblasts (CAFs), which may contribute to the limited efficacy of mesothelin-directed CAR T-cells in early-phase clinical trials
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Broad next generation integrated sequencing of myelofibrosis identifies disease-specific and age-related genomic alterations Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-22 Malathi Kandarpa, Dan Robinson, Yi-Mi Wu, Tingting Qin, Kristen Pettit, Qing Li, Gary Luker, Maureen Sartor, Arul Chinnaiyan, Moshe Talpaz
Purpose: Myeloproliferative neoplasms (MPNs) are characterized by the overproduction of differentiated myeloid cells. Mutations in JAK2, CALR and MPL are considered drivers of Bcr-Abl-ve MPNs, including essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic primary myelofibrosis (prePMF) and overt myelofibrosis (MF). However, how these driver mutations lead to phenotypically distinct and/or
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Selective CDK7 inhibition suppresses cell cycle progression and MYC signaling while enhancing apoptosis in therapy-resistant estrogen receptor positive breast cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-21 Cristina Guarducci, Agostina Nardone, Douglas Russo, Zsuzsanna Nagy, Capucine Heraud, Albert Grinshpun, Qi Zhang, Allegra Freelander, Matthew Joseph. Leventhal, Avery Feit, Gabriella Cohen Feit, Ariel Feiglin, Weihan Liu, Francisco Hermida-Prado, Nikolas Kesten, Wen Ma, Carmine De Angelis, Antonio Morlando, Madison O'Donnell, Sergey Naumenko, Shixia Huang, Quang-De Nguyen, Ying Huang, Luca Malorni
Purpose: Resistance to endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i) is a clinical challenge in estrogen receptor (ER) positive (ER+) breast cancer (BC). Cyclin-dependent kinase 7 (CDK7) is a candidate target in endocrine resistant ER+ BC models and selective CDK7 inhibitors (CDK7i) are in clinical development for the treatment of ER+ BC. Nonetheless, the precise mechanisms responsible for
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Systemic Biological Mechanisms of Neurocognitive Dysfunction in Long-term Survivors of Childhood Hodgkin Lymphoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-21 AnnaLynn M. Williams, Wei Liu, Matthew J. Ehrhardt, Sedigheh Mirzaei Salehabadi, Angela Panoskaltsis-Mortari, Nicholas S. Phillips, Daniel A. Mulrooney, Jamie E. Flerlage, Yutaka Yasui, Deo Kumar Srivastava, Leslie L. Robison, Melissa M. Hudson, Kirsten K. Ness, Noah D. Sabin, Kevin R. Krull
Background: Hodgkin lymphoma (HL) survivors experience neurocognitive impairment despite receiving no central nervous system-directed therapy, though little is known about underlying mechanisms. Methods: HL survivors (n=197) and age-, sex- and race/ethnicity-frequency-matched community controls (n=199) underwent standardized neurocognitive testing, and serum collection. Luminex multiplex or ELISA assays
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Breast Cancer Index and Prediction of Extended Aromatase Inhibitor Therapy Benefit in Hormone Receptor-positive Breast Cancer from the NRG Oncology/NSABP B-42 Trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-20 Eleftherios P. Mamounas, Hanna Bandos, Priya Rastogi, Yi Zhang, Kai Treuner, Peter C. Lucas, Charles E. Geyer, Louis Fehrenbacher, Stephen K. Chia, Adam M. Brufsky, Janice M. Walshe, Gamini S. Soori, Shaker Dakhil, Soonmyung Paik, Sandra M. Swain, Dennis C. Sgroi, Catherine A. Schnabel, Norman Wolmark
Purpose: BCI (H/I) has been shown to predict extended endocrine therapy (EET) benefit. We examined BCI (H/I) for EET benefit prediction in NSABP B-42, which evaluated extended letrozole therapy (ELT) in hormone receptor-positive breast cancer patients after 5 years of ET. Methods: Stratified Cox model was used to analyze RFI as primary endpoint, with DR, BCFI, and DFS, as secondary endpoints. Due to
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Circulating microRNA analysis in a prospective co-clinical trial identifies MIR652-3p as a response biomarker and driver of regorafenib resistance mechanisms in colorectal cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-20 Somaieh Hedayat, Luciano Cascione, David Cunningham, Marta Schirripa, Andrea Lampis, Jens C. Hahne, Nina Tunariu, Sung Pil Hong, Silvia Marchetti, Khurum Khan, Elisa Fontana, Valentina Angerilli, Mia Delrieux, Daniel Nava Rodrigues, Letizia Procaccio, Sheela Rao, David Watkins, Naureen Starling, Ian Chau, Chiara Braconi, Nicos Fotiadis, Ruwaida Begum, Naomi Guppy, Louise Howell, Melanie Valenti, Scott
Background: The multi-kinase inhibitor regorafenib has demonstrated efficacy in chemo-refractory metastatic colorectal cancer (mCRC) patients. However, lack of predictive biomarkers and concerns over significant toxicities hamper the use of regorafenib in clinical practice. Methods: Serial liquid biopsies were obtained at baseline and monthly until disease progression in chemo-refractory mCRC patients
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Unraveling the therapeutic benefit of sequenced chemo-immunotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-19 Paolo D A. Vignali, Jason J. Luke
Combination immune-checkpoint inhibition with chemotherapy is a clinical standard yet concurrent administration may limit the full benefit of immunotherapy by blunting the proliferation and differentiation of CD8 T cells. Identifying patients where sequential chemo-immunotherapy or immunotherapy alone is feasible should be a priority to optimize long-term outcomes.
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Targeting Dendritic Cell Dysfunction to Circumvent anti-PD1 Resistance in Head and Neck Cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-19 Shin Saito, Michihisa Kono, Hoang C.B. Nguyen, Ann Marie Egloff, Cameron Messier, Patrick Lizotte, Cloud Paweletz, Douglas Adkins, Ravindra Uppaluri
Purpose: Neoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed but further insights into the mechanisms underlying resistance and approaches to improve responses are needed. Experimental Design: We integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab
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Clinical activity of transforming growth factor-β inhibitor vactosertib in combination with imatinib in desmoid tumors: a multicenter phase Ib/II study Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-16 Jin-Hee Ahn, Jeeyun Lee, Changhee Park, Seung-Hoon Beom, Seung Hyun Kim, Young Han Lee, Kum-Hee Yun, Jeong Eun Kim, Wooyeol Baek, Yoon Dae Han, Sang Kyum Kim, Hyang Joo Ryu, Inkyung Jung, JooHee Lee, Hong In Yoon, Hyo Song Kim
Purpose:To determine to the activity and safety of TGF-β inhibitor, vactosertib in combination with imatinib in patients with desmoid tumors. Patients and Methods: In this investigator-initiated, open-label, multicenter, phase Ib/II trial, patients with desmoid tumors not amendable to locoregional therapies (surgery and/or radiotherapy) or with disease progression following at least one treatment were
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PPARα Agonism Enhances Immune Response to Radiotherapy while Dietary Oleic Acid Results in Counteraction Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-16 Richard Blake. Ross, Jacob Gadwa, Justin Yu, Laurel B. Darragh, Michael W. Knitz, Diemmy Nguyen, Nicholas A. Olimpo, Khalid N.M. Abdelazeem, Alexander Nguyen, Sophia Corbo, Benjamin Van Court, Jessica Beynor, Brooke Neupert, Anthony J. Saviola, Angelo D'Alessandro, Sana D. Karam
Introduction: Head and neck cancer (HNC) improvements are stagnant, even with advances in immunotherapy. Our previous clinical trial data show altered fatty acid (FA) metabolism correlates with outcome. We hypothesized that pharmacologic and dietary modulation of FA catabolism will impact therapeutic efficacy. Methods: We performed in vivo and in vitro experiments employing PPARα agonism with fenofibrate
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Considering Functional Outcomes as Efficacy Endpoints in Pediatric Low-Grade Glioma Clinical Trials: An FDA Educational Symposium Clin. Cancer Res. (IF 11.5) Pub Date : 2024-02-15 Jason Fangusaro, Robert A. Avery, Michael J. Fisher, Roger J. Packer, Karin S. Walsh, Antoinette Schouten-van Meeteren, Dominik Karres, Diana Bradford, Vishal Bhatnagar, Harpreet Singh, Paul G. Kluetz, Martha Donoghue, Elizabeth S. Duke
In October 2022, the Food and Drug Administration (FDA) Oncology Center of Excellence (OCE) hosted an educational symposium entitled, “Considering Functional Outcomes as Efficacy Endpoints in Pediatric Low-Grade Glioma (pLGG) Clinical Trials.” The symposium brought together patient advocates, regulators from the FDA and the European Medicines Agency (EMA), and an international group of academic thought