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AACR Cancer Progress Report 2024: Inspiring Science-Fueling Progress-Revolutionizing Care. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-18 Patrick A Williams,Sayyed Kaleem Zaidi,Rajarshi Sengupta
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Cancer in multi-lineage mosaic RASopathies due to pathogenic variants in HRAS or KRAS: a systematic review and meta-analysis Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-17 Jonas Windrich, Gina M. Ney, Philip S. Rosenberg, Jung Kim, Martin Zenker, Douglas R. Stewart, Christian P. Kratz
Purpose: To determine the cancer risk and spectrum in patients with multi-lineage mosaic RASopathies with pathogenic variants (PV) in HRAS or KRAS. Methods: We conducted a systematic literature review to identify multi-lineage mosaic RASopathy cases with a PV in HRAS or KRAS to create a retrospective cohort. We calculated cumulative incidence, cancer-free survival and hazard rates (HR) for cancer and
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A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6-Targeting Antibody-Drug Conjugate, in Patients With Small Cell Lung Cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-17 Daniel Morgensztern, Neal Ready, Melissa L. Johnson, Afshin Dowlati, Noura Choudhury, David P. Carbone, Eric Schaefer, Susanne M. Arnold, Sonam Puri, Zofia Piotrowska, Aparna Hegde, Anne C. Chiang, Wade Iams, Anthony Tolcher, Kaname Nosaki, Toshiyuki Kozuki, Tianhong Li, Rafael Santana-Davila, Hiroaki Akamatsu, Haruyasu Murakami, Hiroshi Yokouchi, Song Wang, Jiuhong Zha, Rui Li, Randy R. Robinson,
Purpose: Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy. Patients and Methods: ABBV-011 was administered intravenously once every 3 weeks (Q3W)
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Clonal Hematopoiesis and Clinical Outcomes in Metastatic Castration-Resistant Prostate Cancer Patients Given Androgen Receptor Pathway Inhibitors (Alliance A031201) Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-17 Jeffrey L. Jensen, Olivia Bobek, Irenaeus C. C. Chan, Brian C. Miller, David W. Hillman, Glenn Heller, Todd Druley, Andrew J. Armstrong, Michael J. Morris, Matthew I. Milowsky, Himisha Beltran, Kelly L. Bolton, Catherine C. Coombs
Purpose: Mutations in hematopoietic progenitor cells accumulate with age leading to clonal expansion, termed clonal hematopoiesis (CH). CH in the general population is associated with hematopoietic neoplasms and reduced overall survival (OS), predominantly through cardiovascular adverse events (CVAE). Because androgen receptor pathway inhibitors (ARPI) used in metastatic castration-resistant prostate
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Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-17 Gabriel J. Starrett, Brittany C. Baikie, Benjamin K. Stoff, Hans E. Grossniklaus, Inga Van Buren, Elizabeth G. Berry, Roberto A. Novoa, Kerri E. Rieger, Kavita Y. Sarin, Charles F. Lynch, Michael C. Royer, Mary L. Piaskowski, Isaac Brownell, Emily Y. Chu, Rama Godse, Suephy C. Chen, Kelly J. Yu, Alisa M. Goldstein, Eric A. Engels, Michael R. Sargen
Purpose: Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms
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Update on Whole-body MRI Surveillance for Pediatric Cancer Predisposition Syndromes Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-17 Mary-Louise C. Greer, Lisa J. States, David Malkin, Stephan D. Voss, Andrea S. Doria
Whole-body MRI (WBMRI) is an integral part of screening infants, children and adolescents for pre-symptomatic neoplasms in certain cancer predisposition syndromes (CPS). This includes Li-Fraumeni and Constitutional Mismatch Repair Deficiency syndromes, among others. The list of syndromes where WBMRI adds value, as part of a comprehensive surveillance protocol, continues to evolve in response to new
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Epigenome reprogramming through H3K27 and H3K4 trimethylation as a resistance mechanism to DNA methylation inhibition in BRAFV600E-mutated colorectal cancer. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-13 Hey Min Lee, Ajay Kumar. Saw, Van K. Morris, Stefania Napolitano, Christopher Bristow, Sanjana Srinivasan, Michael Peoples, Alexey Sorokin, Preeti Kanikarla Marie, Jonathan Schulz, Anand K. Singh, Christopher Terranova, Oluwadara Coker, Abhinav Jain, Scott Kopetz, Kunal Rai
Purpose: BRAFV600E-mutated colorectal cancer (CRC) exhibits a strong correlation with DNA hypermethylation suggesting this subgroup of tumors presents unique epigenomic phenotypes. Nonetheless, 5-azacitidine, which inhibits DNA methyltransferase activity, is not efficacious in BRAFV600E CRC in vivo. Experimental Design: We randomized and treated mice implanted with patient-derived tumor xenografts
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MEK inhibitors lead to PDGFR pathway upregulation and sensitize tumors to RAF dimer inhibitors in NF1-deficient malignant peripheral nerve sheath tumor (MPNST) Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-13 Miguel A. Miranda-Román, Cindy J. Lee, Eve Fishinevich, Leili Ran, Amish J. Patel, Juan Yan, Makhzuna N. Khudoynazarova, Sarah Warda, Mohini R. Pachai, Yu Chen, Ping Chi
Purpose: Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive subtype of soft tissue sarcoma with a high propensity to metastasize and extremely limited treatment options. Loss of the RAS-GAP NF1 leads to sustained RAF/MEK/ERK signaling in MPNST. However, single-agent MEK inhibitors (MEKi) have failed to elicit a sustained inhibition of the MAPK signaling pathway in MPNST. Experimental
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Plasma ctDNA as a treatment response biomarker in metastatic cancers: evaluation by the RECIST working group Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-13 Alexander W. Wyatt, Saskia Litière, Francois-Clement Bidard, Luc Cabel, Lars Dyrskjøt, Chris A. Karlovich, Klaus Pantel, Joan Petrie, Reena Philip, Hillary S. Andrews, Paz J. Vellanki, Sofie H. Tolmeijer, Xenia Villalobos Alberu, Christian Alfano, Jan Bogaerts, Emiliano Calvo, Alice P. Chen, Rodrigo A. Toledo, Elisabeth G. E. de Vries, Lesley Seymour, Scott A. Laurie, Elena Garralda
Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The Response Evaluation Criteria in Solid Tumors (RECIST) based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide
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Androgen Deprivation Therapy Drives a Distinct Immune Phenotype in Localized Prostate Cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-13 Matthew C. Dallos, Aleksandar Z. Obradovic, Patrick McCann, Nivedita Chowdhury, Aditya Pratapa, David H. Aggen, Christopher Gaffney, Karen A. Autio, Renu K. Virk, Angelo M. De Marzo, Emmanuel S. Antonarakis, Howard I. Scher, Charles G. Drake, Dana E. Rathkopf
Purpose: Androgen deprivation therapy (ADT) remains the backbone of prostate cancer treatment. Beyond suppression of testosterone and tumor cell growth, emerging evidence suggests ADT also modulates the immune tumor microenvironment (TME). However, a more precise understanding of the timing and intricacies of these immunological shifts is needed. Experimental Design: Here we analyzed 49 primary prostate
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Hepatocellular Carcinoma Immune Microenvironment Analysis: A Comprehensive Assessment with Computational and Classical Pathology Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-12 Caner Ercan, Salvatore Lorenzo. Renne, Luca Di Tommaso, Charlotte K.Y. Ng, Salvatore Piscuoglio, Luigi M. Terracciano
Purpose: The spatial variability and clinical relevance of the tumour immune microenvironment (TIME) are still poorly understood for hepatocellular carcinoma (HCC). Here we aim to develop a deep learning (DL)-based image analysis model for the spatial analysis of immune cell biomarkers, and microscopically evaluate the distribution of immune infiltration. Experimental Design: Ninety-two HCC surgical
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The Epstein-Barr virus nuclear antigen 1 variant associated with nasopharyngeal carcinoma defines the sequence criteria for serologic risk prediction Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-12 Benjamin E. Warner, Japan Patel, Renwei Wang, Jennifer Adams-Haduch, Yu-Tang Gao, Woon-Puay Koh, Ka Wo Wong, Alan K.S. Chiang, Jian-Min Yuan, Kathy H. Y. Shair
Purpose: Antibodies to select Epstein-Barr virus (EBV) proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against EBV nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years pre-diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay. Design: Mammalian-expressed
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TAK1 Promotes an Immunosuppressive Tumor Microenvironment through Cancer-Associated Fibroblast Phenotypic Conversion in Pancreatic Ductal Adenocarcinoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-12 Nan Sheng, Koji Shindo, Kenoki Ohuchida, Tomohiko Shinkawa, Bo Zhang, Haimin Feng, Takeo Yamamoto, Taiki Moriyama, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura
Purpose: We aim to clarify the precise function of Transformed growth factor-beta 1 activated kinase-1 (TAK1) in cancer-associated fibroblasts (CAFs) within human pancreatic ductal adenocarcinoma (PDAC) by investigating its role in cytokine-mediated signaling pathways. Experimental Design: The expression of TAK1 in pancreatic cancer was confirmed by TCGA data and human pancreatic cancer specimens.
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A first-in-human phase 1 study of BXQ-350, a first-in-class sphingolipid metabolism regulator, in patients with advanced/recurrent solid tumors or high-grade gliomas Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-12 Olivier Rixe, John L. Villano, Robert Wesolowski, Anne M. Noonan, Vinay K. Puduvalli, Trisha M. Wise-Draper, Richard Curry, Emrullah Yilmaz, Charlie Cruze, Besim Ogretmen, Gilles Tapolsky, Ray Takigiku
Purpose: BXQ-350, a nanovesicle formulation of Saposin C, is an allosteric sphingolipid metabolism regulator that increases pro-apoptotic ceramide and decreases oncogenic sphingosine-1-phosphate (S1P) levels. We conducted a first-in-human, phase 1 study of BXQ-350. Patients and Methods: Adults (≥18 years old) with advanced/recurrent, treatment-refractory solid tumors or high-grade gliomas received
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Update on Recommendations for Cancer Screening and Surveillance in Children with Genomic Instability Disorders Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-12 Yoshiko Nakano, Roland P. Kuiper, Kim E. Nichols, Christopher C. Porter, Harry Lesmana, Julia Meade, Christian P. Kratz, Lucy A. Godley, Luke D. Maese, Maria Isabel Achatz, Payal P. Khincha, Sharon A. Savage, Andrea S. Doria, Mary-Louise C. Greer, Vivian Y. Chang, Lisa L. Wang, Sharon E. Plon, Michael F. Walsh
Genomic instability disorders are characterized by DNA or chromosomal instability resulting in various clinical manifestations including developmental anomalies, immunodeficiency, and increased risk to develop cancers beginning in childhood. Many of these genomic instability disorders also present with exquisite sensitivity to anticancer treatments such as ionizing radiation and chemotherapy, which
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Metabolic tumor volume response after bridging therapy determines chimeric antigen receptor T-cell outcomes in large B cell lymphoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-11 Harper Hubbeling, Doris Leithner, Emily A. Silverman, Jessica Flynn, Sean Devlin, Gunjan Shah, Beatrice Fregonese, Beatriz Wills, Akshay Bedmutha, Ana Alarcon Tomas, Allison Parascondola, Amethyst Saldia, Ivan Landego, Carla Hajj, Alexander P. Boardman, Parastoo B. Dahi, Arnab Ghosh, Sergio Giralt, Richard J. Lin, Jae Park, Michael Scordo, Gilles Salles, Joachim Yahalom, M. Lia. Palomba, Heiko Schöder
Purpose: Greater disease burden is a well-established predictor of poorer outcomes following chimeric antigen receptor T-cell therapy (CART). While bridging therapy (BT) is widely used between leukapheresis and CAR T infusion, limited data has evaluated the impact of BT on CART outcomes. In this study, we hypothesized that the quantitative dynamics of radiomic cytoreduction during bridging are prognostic
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Second primary malignancies after CAR T-cell therapy: A systematic review and meta-analysis of 5,517 lymphoma and myeloma patients Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-11 Tobias Tix, Mohammad Alhomoud, Roni Shouval, Edward R. Scheffer. Cliff, Miguel-Angel Perales, David M. Cordas dos Santos, Kai Rejeski
Purpose: CAR T-cell therapy is a potent immunotherapy for hematologic malignancies, but patients can develop long-term adverse events including second primary malignancies (SPMs) that impact morbidity and mortality. To delineate the frequency and subtypes of SPMs following CAR-T in lymphoma and myeloma, we performed a systematic review and meta-analysis. Design: A literature search was conducted in
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The intrauterine device: how to deploy this strategy in the molecular world? Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-10 Paul Johannet, Claire F. Friedman
Progestin-based therapy can safely be offered to a subset of patients with atypical endometrial hyperplasia or Grade 1 endometrioid endometrial cancer who desire fertility preservation. A recent study shows that levonorgestrel intrauterine device confers durable clinical benefit and identifies possible immune mechanisms of relapse and resistance.
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ctDNA dynamics and mechanisms of acquired resistance in patients treated with osimertinib with or without bevacizumab from the randomised phase II ETOP-BOOSTER trial Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-09 Ross A. Soo, Urania Dafni, Ji-Youn Han, Byoung Chul Cho, Ernest Nadal, Chong Ming Yeo, Enric Carcereny, Javier de Castro, Maria Angeles Sala, Linda Coate, Mariano Provencio, Christian Britschgi, Patrick Vagenknecht, Georgia Dimopoulou, Roswitha Kammler, Stephen P. Finn, Solange Peters, Rolf A. Stahel
Background: ETOP 10-16 BOOSTER study was a randomised phase II trial of osimertinib and bevacizumab versus osimertinib in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously. Methods: Next generation sequencing (Guardant360®) was conducted in serial plasma samples. The association between ctDNA and efficacy
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FDA Approval Summary: Belzutifan for Patients with Advanced Renal Cell Carcinoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-09 Jaleh Fallah, Brian L. Heiss, Hee-Koung Joeng, Chana Weinstock, Xin Gao, William F. Pierce, Benjamin Chukwurah, Vishal Bhatnagar, Mallorie H. Fiero, Laleh Amiri-Kordestani, Richard Pazdur, Paul G. Kluetz, Daniel L. Suzman
On December 14, 2023, the United States Food and Drug Administration (FDA) approved belzutifan (Welireg, Merck & Co., Inc.) for patients with advanced renal cell carcinoma (RCC) following a programmed death receptor-1 or programmed death-ligand 1 (PD-1/PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). FDA granted traditional approval based on LITESPARK-005
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Tumor-infiltrating lymphocytes in necrotic tumors after melanoma neoadjuvant anti-PD1 therapy correlate with pathological response and recurrence-free survival Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-09 Kevin L. Ma, Tara C. Mitchell, Meaghan Dougher, Cimarron E. Sharon, Gabriella N. Tortorello, David E. Elder, Eric E. Morgan, Phyllis A. Gimotty, Alexander C. Huang, Ravi K. Amaravadi, Lynn M. Schuchter, Ahron Flowers, John T. Miura, Giorgos C. Karakousis, Xiaowei Xu
Purpose: Neoadjuvant anti-PD1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TILs), and more TILs are associated with better treatment response. A major pathological response (MPR) in melanoma after neoadjuvant anti-PD1 therapy usually comprises tumor necrosis and fibrosis. The role of TILs in necrotic tumor necrosis (nTILs) has not been explored. Experimental Design: We performed
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A First-in-Human Study of cinrebafusp alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-05 Sarina Piha-Paul, Shane A. Olwill, Erika Hamilton, Anthony Tolcher, Paula Pohlmann, Stephen V. Liu, Cornelia Wurzenberger, Laura-Carolin Hasenkamp, Eva-Maria Hansbauer, Rachna Shroff, Sara Hurvitz, Anuradha Krishnamurthy, Amita Patnaik, Noah Hahn, Raman Kumar, Manuela Duerr, Markus Zettl, Kayti Aviano, Louis Matis, Ingmar Bruns, Geoffrey Ku
Purpose: 4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, natural killer cells and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety
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FDA Approval Summary: Enfortumab Vedotin Plus Pembrolizumab for Locally Advanced or Metastatic Urothelial Carcinoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-04 Michael H. Brave, William F. Maguire, Chana Weinstock, Hui Zhang, Xin Gao, Fang Li, Jingyu Yu, Wentao Fu, Hong Zhao, William F. Pierce, Elaine Chang, Jeannette Dinin, Mallorie H. Fiero, Nam Atiqur. Rahman, Shenghui Tang, Richard Pazdur, Paul G. Kluetz, Laleh Amiri-Kordestani, Daniel L. Suzman
On December 15, 2023, the FDA granted traditional approval to enfortumab vedotin-ejfv plus pembrolizumab (EV + Pembro) for patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Substantial evidence of effectiveness was obtained from EV-302/KEYNOTE-A39 (NCT04223856), an open-label, randomized, trial evaluating EV + Pembro versus cisplatin or carboplatin plus gemcitabine (Plat +
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Genomic profiling and immune phenotyping of neuroendocrine bladder cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-03 Jingyu Zang, Akezhouli Shahatiaili, Mei-Chun Cai, Di Jin, Peiye Shen, Lei Qian, Lu Zhang, Tianxiang Zhang, Yuchen Wu, Fan Yang, Zheng Wu, Yanli Hou, Yongrui Bai, Jun Xia, Liang Cheng, Ruiyun Zhang, Guanglei Zhuang, Haige Chen
Purpose: Neuroendocrine bladder cancer (NEBC) poses a formidable clinical challenge and attracts keen interests to explore immunotherapy as a viable treatment option. However, a comprehensive immunogenomic landscape has yet to be thoroughly investigated. Experimental Design: Leveraging a long-term cohort of natural NEBC cases, we employed a multimodal approach integrating genomic (n = 19), transcriptomic
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A phase II study of atezolizumab, pertuzumab, and high-dose trastuzumab for central nervous system metastases in patients with HER2-positive breast cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-03 Antonio Giordano, Priya U. Kumthekar, Qingchun Jin, Busem Binboga Kurt, Siyang Ren, Tianyu Li, Jose Pablo. Leone, Elizabeth A. Mittendorf, Alyssa M. Pereslete, Laura Sharp, Raechel Davis, Molly DiLullo, Nabihah Tayob, Erica L. Mayer, Eric P. Winer, Sara M. Tolaney, Nancy U. Lin
Purpose: Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements
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Understanding and Overcoming Resistance to Selective FGFR inhibitors Across FGFR2-Driven Malignancies Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-03 Francesco Facchinetti, Yohann Loriot, Floriane Braye, Damien Vasseur, Rastislav Bahleda, Ludovic Bigot, Rémy Barbé, Catline Nobre, David Combarel, Stefan Michiels, Antoine Italiano, Cristina Smolenschi, Lambros Tselikas, Jean-Yves Scoazec, Santiago Ponce-Aix, Benjamin Besse, Fabrice Andre, Ken A. Olaussen, Antoine Hollebecque, Luc Friboulet
Purpose: Understanding resistance to selective FGFR inhibitors is crucial to improve the clinical outcomes of patients with FGFR2-driven malignancies. Experimental Design: We analyzed sequential ctDNA, +/- WES or targeted NGS on tissue biopsies from patients with tumors harboring activating FGFR2 alterations progressing on pan-FGFR-selective inhibitors, collected in the prospective UNLOCK program.
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Inhibition of Aberrantly Overexpressed Polo-like Kinase 4 Is a Potential Effective Treatment for DNA Damage Repair-Deficient Uterine Leiomyosarcoma. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-03 Horace H Y Lee,Kin Long Chow,Ho Shing Wong,Tsz Yan Chong,Alice S T Wong,Grace H W Cheng,Jasmine M K Ko,Hoi Cheong Siu,Maximus C F Yeung,Michael S Y Huen,Ka Yu Tse,Mark R Bray,Tak Wah Mak,Suet Yi Leung,Philip P C Ip
PURPOSE Uterine leiomyosarcoma (LMS) is an aggressive sarcoma and a subset of which exhibits DNA repair defects. Polo-like kinase 4 (PLK4) precisely modulates mitosis, and its inhibition causes chromosome missegregation and increased DNA damage. We hypothesize that PLK4 inhibition is an effective LMS treatment. EXPERIMENTAL DESIGN Genomic profiling of clinical uterine LMS samples was performed, and
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Update on Pediatric Cancer Surveillance Recommendations for Patients with Neurofibromatosis Type 1, Noonan Syndrome, CBL Syndrome, Costello Syndrome, and Related RASopathies Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-29 Melissa R. Perrino, Anirban Das, Sarah R. Scollon, Sarah G. Mitchell, Mary-Louise C. Greer, Marielle E. Yohe, Jordan R. Hansford, Jennifer M. Kalish, Kris Ann P. Schultz, Suzanne P. MacFarland, Wendy K. Kohlmann, Philip J. Lupo, Kara N. Maxwell, Stefan M. Pfister, Rosanna Weksberg, Orli Michaeli, Marjolijn C. J. Jongmans, Gail E. Tomlinson, Jack Brzezinski, Uri Tabori, Gina M. Ney, Karen W. Gripp,
Neurofibromatosis type 1 (NF1), Noonan syndrome and related syndromes, grouped as the RASopathies, result from dysregulation of the RAS-MAPK pathway and demonstrate varied multisystemic clinical phenotypes. Together the RASopathies are among the more prevalent genetic cancer predisposition syndromes and require nuanced clinical management. When compared to the general population, children with RASopathies
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Exploiting WEE1 kinase activity as FUS::DDIT3-dependent therapeutic vulnerability in myxoid liposarcoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-29 Lorena Heinst, Kwang Seok Lee, Ruth Berthold, Ilka Isfort, Svenja Wosnig, Anna Kuntze, Susanne Hafner, Bianca Altvater, Claudia Rössig, Pierre Åman, Eva Wardelmann, Claudia Scholl, Wolfgang Hartmann, Stefan Fröhling, Marcel Trautmann
Purpose: The pathognomonic FUS::DDIT3 fusion protein drives myxoid liposarcoma (MLS) tumorigenesis via aberrant transcriptional activation of oncogenic signaling. Since FUS::DDIT3 has so far not been pharmacologically tractable to selectively target MLS cells, this study investigated the functional role of the cell cycle regulator WEE1 as novel FUS::DDIT3‑dependent therapeutic vulnerability in MLS
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Pediatric cancer screening in hereditary gastrointestinal cancer risk syndromes: An update from the AACR Childhood Cancer Predisposition Working Group Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-27 Suzanne P. MacFarland, Kerri Becktell, Kami Wolfe. Schneider, Roland P. Kuiper, Harry Lesmana, Julia Meade, Kim E. Nichols, Christopher C. Porter, Sharon A. Savage, Kris Ann Schultz, Hamish Scott, Lisa States, Uri Tabori, Chieko Tamura, Gail Tomlinson, Kristin Zelley, Carol Durno, Andrew Bauer, Sharon E. Plon
Gastrointestinal (GI) polyposis and cancer in pediatric patients is frequently due to an underlying hereditary cancer risk syndrome requiring ongoing cancer screening. Identification of at-risk patients through family history, clinical features of syndrome, or symptom onset ensures appropriate cancer risk assessment and management in childhood and beyond. In this 2024 perspective, we outline updates
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Translational Imaging in Cerebral Tumors Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-23 Alexey Surov, Jan Borggrefe
Despite emerging possibilities of molecular histopathologic characterization, multiparamateric magnetic resonance imaging (MTP) plays a key role in the diagnosis and classification of cerebral tumors. Imaging may also provide additional information about relevant histopathological features of these tumors.
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Targeted therapies, novel antibodies, and immunotherapies in advanced non-small cell lung cancer: clinical evidence and drug approval patterns Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-23 Maren Ulrike. Koban, Markus Hartmann, Georgios Amexis, Pedro Franco, Laura Huggins, Imran Shah, Niki Karachaliou
Since 2011, the U.S. FDA has approved 30 new drugs for use in advanced non-small-cell lung cancer (NSCLC), mainly comprising tyrosine kinase inhibitors and immune checkpoint inhibitors. NSCLC with oncogene driver alterations is amenable to treatment with targeted drugs, usually small molecule inhibitors. In these cases, the demonstration of high overall response rates, coupled with a lasting duration
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Genomic and epigenomic analysis of plasma cell-free DNA identifies stemness features associated with worse survival in lethal prostate cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-23 Pradeep S. Chauhan, Irfan Alahi, Savar Sinha, Elisa M. Ledet, Ryan Mueller, Jessica Linford, Alexander L. Shiang, Jace Webster, Lilli Greiner, Breanna Yang, Gabris Ni, Ha X. Dang, Debanjan Saha, Ramandeep K. Babbra, Wenjia Feng, Peter K. Harris, Faridi Qaium, Dzifa Y. Duose, Alexander Sanchez-Espitia, Alexander D. Sherry, Ellen B. Jaeger, Patrick J. Miller, Sydney A. Caputo, Jacob J. Orme, Fabrice
Purpose: Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSIs) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms remain ill-understood. Experimental Design: We applied targeted cell-free DNA sequencing to 126 mCRPC patients from three academic cancer centers
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Genetic Screen in a Pre-Clinical Model of Sarcoma Development Defines Drivers and Therapeutic Vulnerabilities Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-23 Jack Freeland, Maria Muñoz, Edmond O'Donnell, Justin Langerman, Morgan Darrow, Jessica Bergonio, Julissa Suarez-Navarro, Steven Thorpe, Robert Canter, R. Lor Randall, Kathrin Plath, Kermit L. Carraway, Owen N. Witte, Thomas G. Graeber, Janai R. Carr-Ascher
Purpose: High-grade complex karyotype sarcomas are a heterogeneous group of tumors with a uniformly poor prognosis. Within complex karyotype sarcomas, there are innumerable genetic changes but identifying those that are clinically relevant has been challenging. Experimental Design: To address this, we utilized a pooled genetic screening approach, informed by TCGA data, to identify key drivers and modifiers
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KIR2DL2/DL3+NKs and Helios+Tregs in peripheral blood predict nivolumab response in patients with metastatic renal cell cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-21 Sara Santagata, Anna Maria Trotta, Crescenzo D'Alterio, Maria Napolitano, Giuseppina Rea, Marilena Di Napoli, Luigi Portella, Caterina Ieranò, Giuseppe Guardascione, Elisabetta Coppola, Christophe Caux, Bertrand Dubois, Helen J. Boyle, Joan Carles, Sabrina Rossetti, Rosa Azzaro, Florinda Feroce, Sisto Perdonà, Mario Fordellone, Anna Maria Bello, Daniela Califano, Paolo Chiodini, Sandro Pignata, Stefania
Purpose: To identify predictive factors of nivolumab sensitivity, peripheral blood NKs and Tregs were evaluated in patients with metastatic renal cell carcinoma (mRCC) enrolled in the REVOLUTION trial. Experimental design: 57 mRCCs being treated with nivolumab, as at least second-line of therapy (REV), and 62 healthy donors (HDs) were longitudinally evaluated (0-1-3-6-12 months) for peripheral NKs
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A PHASE 1 FIRST-IN-HUMAN STUDY OF THE MCL-1 INHIBITOR AZD5991 IN PATIENTS WITH RELAPSED/REFRACTORY HEMATOLOGIC MALIGNANCIES Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-21 Pinkal Desai, Sagar Lonial, Amanda Cashen, Manali Kamdar, Ian Flinn, Susan O'Brien, Jacqueline S. Garcia, Neha Korde, Javid Moslehi, Margaret Wey, Patricia Cheung, Shringi Sharma, Damilola Olabode, Hong Chen, Firasath Ali Syed, Mary Liu, Marcio Andrade-Campos, Tapan M. Kadia, James S. Blachly
Background: AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics (PK), and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory (R/R) hematologic malignancies. Methods: In the monotherapy cohort (n=61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or
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Pembrolizumab and cabozantinib in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC): long-term survival update with a biomarker analysis Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-21 Nabil F. Saba, Ritu Chaudhary, Kedar Kirtane, Angelo Marra, Asari Ekpenyong, Ashley McCook-Veal, Nicole C. Schmitt, Jennifer H. Gross, Mihir R. Patel, Jill Remick, James E. Bates, Mark W. McDonald, Soumon F. Rudra, William A. Stokes, Maria Biernacki, Xiaofei Song, Robbert J.C. Slebos, Yuan Liu, Conor E. Steuer, Dong M. Shin, Yong Teng, Christine H. Chung
Purpose: Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) have immunomodulatory properties and improve clinical outcomes in combination with anti-PD-1 therapy. We report the long-term efficacy and safety of pembrolizumab
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Novel ERBB2 Variant Potentially Associated with Resistance against Anti-HER2 Monoclonal Antibody-Based Therapy in ERBB2-Amplified Metastatic Colorectal Cancer. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-09-13 Naoko Iida,Mitsuho Imai,Wataru Okamoto,Takeshi Kato,Taito Esaki,Ken Kato,Yoshito Komatsu,Satoshi Yuki,Toshiki Masuishi,Tomohiro Nishina,Hiromichi Ebi,Hiroya Taniguchi,Norio Nonomura,Yu Sunakawa,Manabu Shiozawa,Kentaro Yamazaki,Shogen Boku,Hideaki Bando,Yuichi Shiraishi,Maki Kobayashi,Hiroki Goto,Akihiro Sato,Satoshi Fujii,Takayuki Yoshino,Yoshiaki Nakamura
PURPOSE HER2-targeted therapies in ERBB2-amplified metastatic colorectal cancer (mCRC) are effective; however, a notable portion of patients do not respond to treatment, and secondary resistance occurs in most patients receiving these treatments. The purpose of this study was to investigate determinants of treatment efficacy and resistance in patients with ERBB2-amplified mCRC who received HER2-targeted
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Chemotherapy drives tertiary lymphoid structures that correlate with ICI-responsive TCF1+CD8+ T cells in metastatic ovarian cancer. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-20 Tereza Lanickova,Michal Hensler,Lenka Kasikova,Sarka Vosahlikova,Artemis Angelidou,Josef Pasulka,Hannah Griebler,Jana Drozenova,Katerina Mojzisova,Ann Vankerckhoven,Jan Laco,Aleš Ryška,Pavel Dundr,Roman Kocian,David Cibula,Tomas Brtnicky,Petr Skapa,Francis Jacob,Marek Kovar,Ivan Praznovec,Iain A McNeish,Michael J Halaska,Lukas Rob,An Coosemans,Sandra Orsulic,Lorenzo Galluzzi,Radek Spisek,Jitka Fucikova
PURPOSE Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICIs) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to
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The infiltrative margins in glioblastoma: important is what has been left behind. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-20 Philipp Karschnia,Joerg C Tonn,Daniel P Cahill
Supramaximal resection beyond the contrast-enhancing tumor borders represents an emerging surgical strategy for patients with newly diagnosed glioblastoma. A recent study provides evidence detailing the interactive effects of more aggressive surgery with other clinical predictors of outcome, supporting guidance for surgical decision-making and informing clinical trialists about the need to stratify
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YAP1 status defines two intrinsic subtypes of LCNEC with distinct molecular features and therapeutic vulnerabilities Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-16 C. Allison Stewart, Lixia Diao, Yuanxin Xi, Runsheng Wang, Kavya Ramkumar, Alejandra G. Serrano, Azusa Tanimoto, B. Leticia Rodriguez, Benjamin B. Morris, Li Shen, Bingnan Zhang, Yan Yang, Samera H. Hamad, Robert J. Cardnell, Alberto Duarte, Moushumi Sahu, Veronica Y. Novegil, Bernard E. Weissman, Michael Frumovitz, Neda Kalhor, Luisa Solis Soto, Pedro da Rocha, Natalie Vokes, Don L. Gibbons, Jing
Purpose: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine malignancy that, like small cell lung cancer (SCLC), is associated with an absence of druggable oncogenic drivers and dismal prognosis. In contrast to SCLC, however, there is little evidence to guide optimal treatment strategies which are often adapted from SCLC and non-small cell lung cancer (NSCLC) approaches. Experimental
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The Impact of Li Fraumeni and Germline Retinoblastoma Mutations on Leiomyosarcoma Initiation, Outcomes and Genetic Testing Recommendations Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-16 Josephine K. Dermawan, David H. Abramson, Sarah Chiang, Martee L. Hensley, William D. Tap, Sujana Movva, Robert G. Maki, Diana Mandelker, Cristina R. Antonescu
Purpose: Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous, occurring mostly in sporadic but also syndromic settings. The role of pathogenic germline variants (PGV) as LMS drivers and impact on outcome remain uncertain. Experimental Design: We perform a comprehensive clinicopathologic and molecular analysis using a tumor-normal DNA next-generation sequencing assay (MSK-IMPACT) of germline-associated
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Transcriptomic heterogeneity of EGFR-mutant non-small cell lung cancer evolution towards small cell lung cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-16 Songji Oh, Jaemoon Koh, Tae Min Kim, Soyeon Kim, Jeonghwan Youk, Miso Kim, Bhumsuk Keam, Yoon Kyung Jeon, Ja-Lok Ku, Dong-Wan Kim, Doo Hyun Chung, Dae Seog Heo
Purpose: Histological transformation from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a key mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs). However, transcriptomic changes between NSCLC and transformed SCLC (t-SCLC) remain unexplored. Experimental Design: We conducted whole transcriptome analysis of 59 regions
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Remote Neuroinflammation in Newly Diagnosed Glioblastoma Correlates with Unfavorable Clinical Outcome Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-16 Laura M. Bartos, Stefanie Quach, Valerio Zenatti, Sabrina V. Kirchleitner, Jens Blobner, Karin Wind-Mark, Zeynep Ilgin. Kolabas, Selin Ulukaya, Adrien Holzgreve, Viktoria C. Ruf, Lea H. Kunze, Sebastian T. Kunte, Leonie Hoermann, Marlies Härtel, Ha Eun Park, Mattes Groß, Nicolai Franzmeier, Artem Zatcepin, Adrian Zounek, Lena Kaiser, Markus J. Riemenschneider, Robert Perneczky, Boris-Stephan Rauchmann
Purpose: Current therapy strategies still provide only limited success in the treatment of glioblastoma, the most frequent primary brain tumor in adults. In addition to the characterization of the tumor microenvironment, global changes in brain of patients with glioblastoma have been described. However, the impact and molecular signature of neuroinflammation distant of the primary tumor site have not
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Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a predictive biomarker for immune checkpoint inhibitors in biliary tract cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-16 Yeong Hak Bang, Choong-kun Lee, Kyunghye Bang, Hyung-Don Kim, Kyu-pyo Kim, Jae Ho Jeong, Inkeun Park, Baek-Yeol Ryoo, Dong Ki Lee, Hye Jin Choi, Taek Chung, Seung Hyuck Jeon, Eui-Cheol Shin, Chiyoon Oum, Seulki Kim, Yoojoo Lim, Gahee Park, Chang Ho Ahn, Taebum Lee, Richard S. Finn, Chan-Young Ock, Jinho Shin, Changhoon Yoo
Purpose: Anti-PD-1/L1 has been demonstrated for its efficacy when combined with cytotoxic chemotherapy in randomized phase 3 trials for advanced biliary tract cancer (BTC). However, no biomarker predictive of benefit has been established for anti-PD-1/L1 in BTC. Here, we evaluated tumor-infiltrating lymphocytes (TILs) using artificial intelligence-powered immune phenotype (AI-IP) analysis in advanced
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Editor's Note: 4E-Binding Protein 1, a Cell Signaling Hallmark in Breast Cancer That Correlates with Pathologic Grade and Prognosis. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Federico Rojo,Laura Najera,José Lirola,José Jiménez,Marta Guzmán,M Dolors Sabadell,Jose Baselga,Santiago Ramon Y Cajal
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Editor's Note: Detection of Wilms' Tumor Antigen-Specific CTL in Tumor-Draining Lymph Nodes of Patients with Early Breast Cancer. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Roopinder Gillmore,Shao-An Xue,Angelika Holler,Jaspal Kaeda,Dimitri Hadjiminas,Vourneen Healy,Roberto Dina,Suzanne C Parry,Ilaria Bellantuono,Yasmeen Ghani,R Charles Coombes,Jonathan Waxman,Hans J Stauss
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Nivolumab with or without Ipilimumab Combined with Stereotactic Body Radiotherapy in Patients with Metastatic Biliary Tract Cancer: A Randomized Phase 2 Study. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Alice Markussen,Julia S Johansen,Finn O Larsen,Susann Theile,Jane P Hasselby,Gro L Willemoe,Torben Lorentzen,Kasper Madsen,Estrid Høgdall,Tim S Poulsen,Eva E Wilken,Poul Geertsen,Claus P Behrens,Inge M Svane,Dorte Nielsen,Inna M Chen
PURPOSE The purpose of this study was to evaluate the clinical benefits of nivolumab with/without ipilimumab combined with stereotactic body radiotherapy (SBRT) in patients with pretreated metastatic biliary tract cancer (mBTC). PATIENTS AND METHODS The study was a phase 2 randomized trial with Simon's optimal two-stage design requiring 36 evaluable patients per group after second stage. Sixty-one
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A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Emiri O Takaki,Kunihiko Kiyono,Yutaka Obuchi,Takeshi Yamauchi,Takashi Watanabe,Hideki Matsumoto,Miho Karimine,Yuki Kuniyoshi,Shingo Nishikori,Fumiharu Yokoyama,Hikaru Nishimori,Hiroshi Nabeshima,Kazuhide Nakamura
PURPOSE Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor with KIT or PDGFRA driver mutations, is typically treated with tyrosine kinase inhibitors (TKI). However, resistance to TKIs due to secondary mutations is a common challenge in advanced GISTs. In addition, there are currently no effective therapies for several other molecular subtypes, such as succinate dehydrogenase-deficient
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Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients with Early Colorectal Cancer from the UK TRACC Part B Study. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Susanna Slater,Annette Bryant,Maria Aresu,Ruwaida Begum,Hsiang-Chi Chen,Clare Peckitt,Retchel Lazaro-Alcausi,Paul Carter,Gayathri Anandappa,Shelize Khakoo,Lucinda Melcher,Vanessa Potter,Francisca M Marti,Joesph Huang,Graham Branagan,Nicol George,Muti Abulafi,Sarah Duff,Ashraf Raja,Ashish Gupta,Nicholas West,Leslie Bucheit,Thereasa Rich,Ian Chau,David Cunningham,Naureen Starling,
PURPOSE The absence of postoperative circulating tumor DNA (ctDNA) identifies patients with resected colorectal cancer (CRC) with low recurrence risk for adjuvant chemotherapy (ACT) de-escalation. Our study presents the largest resected CRC cohort to date with tissue-free minimal residual disease (MRD) detection. EXPERIMENTAL DESIGN TRACC (tracking mutations in cell-free tumor DNA to predict relapse
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FDA Approval Summary: Durvalumab and Pembrolizumab, Immune Checkpoint Inhibitors for the Treatment of Biliary Tract Cancer. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Sandra J Casak,Vaibhav Kumar,Chi Song,Mengdie Yuan,Anup K Amatya,Joyce Cheng,Pallavi S Mishra-Kalyani,Shenghui Tang,Steven J Lemery,Doris Auth,Gina Davis,Paul G Kluetz,Richard Pazdur,Lola A Fashoyin-Aje
On September 2, 2022, the Food and Drug Administration (FDA) approved durvalumab in combination with cisplatin and gemcitabine, for the treatment of patients with unresectable or metastatic biliary tract cancers (BTC). On October 31, 2023, the FDA approved pembrolizumab in combination with cisplatin and gemcitabine for the same indication. Approvals were based on two randomized, multiregional, placebo-controlled
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A Novel Approach to Quantify Heterogeneity of Intrahepatic Cholangiocarcinoma: The Hidden-Genome Classifier. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Yi Song,Thomas Boerner,Esther Drill,Paul Shin,Sandeep Kumar,Carlie Sigel,Andrea Cercek,Nancy Kemeny,Ghassan Abou-Alfa,Christine Iacobuzio-Donahue,Darren Cowzer,Nikolaus Schultz,Henry Walch,Vinod Balachandran,Bas Groot Koerkamp,Peter Kingham,Kevin Soares,Alice Wei,Michael D'Angelica,Jeffrey Drebin,Rohit Chandwani,James J Harding,William Jarnagin
PURPOSE Intrahepatic cholangiocarcinoma (IHC) is a heterogeneous tumor. The hidden-genome classifier, a supervised machine learning-based algorithm, was used to quantify tumor heterogeneity and improve classification. EXPERIMENTAL DESIGN A retrospective review of 1,370 patients with IHC, extrahepatic cholangiocarcinoma (EHC), gallbladder cancer (GBC), hepatocellular carcinoma (HCC), or biphenotypic
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Targeting GPC2 on Intraocular and CNS Metastatic Retinoblastomas with Local and Systemic Delivery of CAR T Cells. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Guillem Pascual-Pasto,Brendan McIntyre,Anna M Giudice,Fatemeh Alikarami,Amanda Morrissey,Stephanie Matlaga,Ted J Hofmann,Victor Burgueño,Kyra Harvey,Daniel Martinez,Amish C Shah,Jessica B Foster,Jennifer Pogoriler,Ralph C Eagle,Angel M Carcaboso,Carol L Shields,Ann-Marie Leahey,Kristopher R Bosse
PURPOSE Retinoblastoma is the most common intraocular malignancy in children. Although new chemotherapeutic approaches have improved ocular salvage rates, novel therapies are required for patients with refractory intraocular and metastatic disease. Chimeric antigen receptor (CAR) T cells targeting glypican-2 (GPC2) are a potential new therapeutic strategy. EXPERIMENTAL DESIGN GPC2 expression and its
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An Evaluation of Novel Oncology Approvals with a PMR/C for Assessing Data in Racial and Ethnic Populations Underrepresented in Premarket Clinical Trials. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Grace Collins,Hillary S Andrews,Brittany McKelvey,Carrigan Rice,Jeff D Allen,Mark D Stewart
Clinical trials supporting oncology drug approvals frequently underrepresent diverse racial and ethnic populations. Recent policies have focused on ensuring premarket clinical trials are more inclusive and representative of racial and ethnic diversity in the general U.S. population or intended patient population; however, recent U.S. Food and Drug Administration (FDA) guidance on postmarketing approaches
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Missense Mutations in Myc Box I Influence Nucleocytoplasmic Transport to Promote Leukemogenesis. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Nancy B J Arthur,Keegan A Christensen,Kathleen Mannino,Marianna B Ruzinova,Ashutosh Kumar,Agata Gruszczynska,Ryan B Day,Petra Erdmann-Gilmore,Yiling Mi,Robert Sprung,Conner R York,Robert R Townsend,David H Spencer,Stephen M Sykes,Francesca Ferraro
PURPOSE Somatic missense mutations in the phosphodegron domain of the MYC gene (MYC Box I or MBI) are detected in the dominant clones of a subset of patients with acute myeloid leukemia (AML), but the mechanisms by which they contribute to AML are unknown. EXPERIMENTAL DESIGN To investigate the effects of MBI MYC mutations on hematopoietic cells, we employed a multi-omic approach to systematically
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FDA Approval Summary: Repotrectinib for Locally Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Michael I Barbato,Diana Bradford,Yi Ren,Stephanie L Aungst,Claudia P Miller,Lili Pan,Jeanne F Zirkelbach,Yangbing Li,Youwei Bi,Jianghong Fan,Manuela Grimstein,Sarah E Dorff,Anup K Amatya,Pallavi S Mishra-Kalyani,Barbara Scepura,Peter Schotland,Opeyemi Udoka,Idara Ojofeitimi,John K Leighton,Nam A Rahman,Richard Pazdur,Harpreet Singh,Paul G Kluetz,Nicole Drezner
On November 15, 2023, the U.S. Food and Drug Administration (FDA) granted traditional approval to repotrectinib (Augtyro, Bristol Myers Squibb Corporation) for the treatment of adult patients with locally advanced or metastatic receptor tyrosine kinase encoded by the ROS1 gene (ROS1)-positive non-small cell lung cancer (NSCLC). The approval was based on TRIDENT-1, a single-arm trial with multiple cohorts
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Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Darrell Green,Roelof van Ewijk,Elisa Tirtei,Dimosthenis Andreou,Fredrik Baecklund,Daniel Baumhoer,Stefan S Bielack,Rajesh Botchu,Kjetil Boye,Bernadette Brennan,Michael Capra,Lucia Cottone,Uta Dirksen,Franca Fagioli,Natalia Fernandez,Adrienne M Flanagan,Marco Gambarotti,Nathalie Gaspar,Hans Gelderblom,Craig Gerrand,Anne Gomez-Mascard,Jendrik Hardes,Stefanie Hecker-Nolting,Edita Kabickova,Leo Kager,Jukka
Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment
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GD2 Target Antigen and CAR T Cells: Does It Take More Than Two to Tango? Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Franco Locatelli,Concetta Quintarelli
Over the past decade, chimeric antigen receptor T cells have emerged as a breakthrough cancer therapy in selected hematologic malignancies. Translating the success of this therapy to solid tumors is challenging. In this issue, we discuss strategies potentially useful to increase the chimeric antigen receptor T-cell efficacy in this clinical indication. See related article by Fischer-Riepe et al., p
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Double-Stranded RNA to Mimic Viral Infection for Cancer Immunotherapy. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Ana Martínez-Riaño,Laura Mosteo,Paula Molero-Glez,Iván Márquez-Rodas,Ignacio Melero
The presence of moieties denoting viral infection is crucial to mount powerful cytotoxic T-cell immune responses acting through innate receptors such as Toll-like receptor 3. For cancer immunotherapy, several safe analogues of viral double-stranded RNA are under clinical development following compelling evidence for efficacy in mouse models. See related article by van Eijck et al., p. 3447.
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Optimizing ATR Inhibition and Cisplatin Synergy in Ewing Sarcoma. Clin. Cancer Res. (IF 10.0) Pub Date : 2024-08-15 Shunya Ohmura,Thomas G P Grünewald
EWSR1::FLI1-mediated dysregulation of cellular machinery opens up potential new avenues for Ewing sarcoma treatment. A recent study demonstrates that pharmacologic ATR kinase inhibition dramatically synergizes with low-dose cisplatin through EWSR1::FLI1-dependent rewiring of transcription, DNA repair, and translation machinery, which could maximize the therapeutic window of the combinatory therapy