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Gene-expression assays to tailor adjuvant endocrine therapy for HR+/HER2- breast cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-24 Michele Bottosso, Federica Miglietta, Grazia Maria. Vernaci, Tommaso Giarratano, Maria Vittoria Dieci, Valentina Guarneri, Gaia Griguolo
Adjuvant endocrine therapy represents the standard of care for almost all HR+/HER2- breast cancers and different agents and durations are currently available. In this context, the tailoring and optimization of adjuvant endocrine treatment by reducing unnecessary toxic treatment while taking into account the biological heterogeneity of HR+/HER2- breast cancer represents a clinical priority. There is
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Fraction dose escalation of hypofractionated radiotherapy with concurrent chemotherapy and subsequent consolidation immunotherapy in locally advanced non-small cell lung cancer: a phase 1 study Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Rui Zhou, FangJie Liu, HongMei Zhang, DaQuan Wang, PengXin Zhang, ShiYang Zheng, YiMei Liu, Li Chen, JinYu Guo, YingYi Zou, Yu-Ming Rong, Hui Liu, Bo Qiu
Purpose: This phase 1 trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Patients and Methods: Split-course hypo-RT and hypo-boost combined with concurrent chemotherapy
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Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Mario E. Lacouture, Elena Goleva, Neil Shah, Veronica Rotemberg, Lukas Kraehenbuehl, Kwami F. Ketosugbo, Taha Merghoub, Tara Maier, Alexander Bang, Stephanie Gu, Trina Salvador, Andrea P. Moy, Taras Lyubchenko, Olivia Xiao, Clifton F. Hall, Evgeny Berdyshev, James Crooks, Ryan Weight, Jeffrey A. Kern, Donald Y.M. Leung
Purpose: Immune-related cutaneous adverse events (ircAEs) occur in ≥50% of patients treated with checkpoint inhibitors (CPI), but mechanisms are poorly understood. Experimental Design: Phenotyping/biomarker analyses were conducted in 200 patients on CPIs (139 with ircAEs, 61 without, control) to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies
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FLT3 agonists and secondary hematopoietic malignancies: a potential class effect Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Henry W. Raeder, Michael W. Drazer
Expansion of cDC cells via FLT3 agonism has promising therapeutic potential in the treatment of advanced solid tumors. Here, we discuss the results of a clinical trial using GS-3583, an FLT3 agonist, that was stopped after a patient in the study developed acute myeloid leukemia.
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Classifying glioma via liquid biopsy--progress towards an unmet clinical need Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Kalil G. Abdullah
The diagnosis and classification of glioma by liquid biopsy represents a critical unmet need in neuro oncology. A recent study demonstrates targeted next generation sequencing (NGS) of cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) as an evolving option for liquid biopsy in patients with glioma.
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A First-in-Human Phase 1 Study of a Tumor-Directed RNA-Interference Drug against HIF2α in Patients with Advanced Clear Cell Renal Cell Carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 James Brugarolas, Gregory Obara, Kathryn E. Beckermann, Brian Rini, Elaine T. Lam, James Hamilton, Thomas Schluep, Min Yi, So Wong, Zhongping Lily Mao, Erick Gamelin, Nizar M. Tannir
Purpose: ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell carcinoma (ccRCC). The aims of this Phase 1 study (AROHIF21001) were to evaluate safety, tolerability, pharmacokinetics, and establish a recommended Phase 2 dose. Patients and Methods: Subjects with ccRCC and progressive disease
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Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Dickran Kazandjian, Benjamin Diamond, Marios Papadimitriou, Elizabeth Hill, Romanos Sklavenitis-Pistofidis, Bachisio Ziccheddu, Patrick Blaney, Monika Chojnacka, Michael Durante, Kylee Maclachlan, Ryan Young, Saad Usmani, Faith Davies, Gad Getz, Irene Ghobrial, Neha Korde, Gareth Morgan, Francesco Maura, Ola Landgren
PURPOSE: Early intervention for High-Risk Smoldering Multiple Myeloma (HR-SMM) achieves deep and prolonged responses. It is unclear if beneficial outcomes are due to treatment of less complex, susceptible disease or inaccuracy in clinical definition of cases entered. EXPERIMENTAL DESIGN: Here, we interrogated whole genome and whole exome sequencing for 54 patients across two HR-SMM interventional studies
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A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-19 Ji Won Han, Soon Kyu Lee, Jung Hyun Kwon, Soon Woo Nam, Hyun Yang, Si Hyun Bae, Ji Hoon Kim, Heechul Nam, Chang Wook Kim, Hae Lim Lee, Hee Yeon Kim, Sung Won Lee, Ahlim Lee, U Im Chang, Do Seon Song, Seok-Hwan Kim, Myeong Jun Song, Pil Soo Sung, Jong Young Choi, Seung Kew Yoon, Jeong Won Jang
Background: Given its heterogeneity and diverse clinical outcomes, precise subclassification of BCLC-C hepatocellular carcinoma (HCC) is required for appropriately determining patient prognosis and selecting treatment. Methods: We recruited 2,626 patients with BCLC-C stage HCC from multiple centers, comprising training/test (n=1,693) and validation cohorts (n=933). The XGBoost was chosen for maximum
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A Cohort Study to Evaluate Genetic Predictors for Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS): Results from ECOG-ACRIN E1Z11 Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-19 Vered Stearns, Opeyemi A. Jegede, Victor Tsu-Shih. Chang, Todd C. Skaar, Jeffrey L. Berenberg, Ranveer Nand, Atif Shafqat, Nisha Lassi. Jacobs, William Luginbuhl, Paul Gilman, Al B. Benson, Judie R. Goodman, Gary L. Buchschacher, N. Lynn. Henry, Charles L. Loprinzi, Patrick J. Flynn, Edith P. Mitchell, Michael Jordan. Fisch, Joseph A. Sparano, Lynne I. Wagner
Purpose: Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS) are common and frequently lead to AI discontinuation. Single nucleotide polymorphisms (SNPs) in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate associations between 10 SNPs and AI discontinuation due to AIMSS. Patients and Methods: Postmenopausal
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Integrating multisector molecular characterization into personalized peptide vaccine design for patients with newly diagnosed glioblastoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-19 Tanner M. Johanns, Elizabeth A.R. Garfinkle, Katherine E. Miller, Alexandra J. Livingstone, Kaleigh F. Roberts, Lakshmi Prakruthi Rao Venkata, Joshua L. Dowling, Michael R. Chicoine, Ralph G. Dacey, Gregory J. Zipfel, Albert H. Kim, Elaine R. Mardis, Gavin P. Dunn
Purpose: Glioblastoma (GBM) patient outcomes remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits
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Low-dose ionizing γ-radiation elicits the extrusion of neutrophil extracellular traps Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Alvaro Teijeira, Saray Garasa, Maria C. Ochoa, Sandra Sanchez-Gregorio, Gabriel Gomis, Carlos Luri-Rey, Rafael Martinez-Monge, Beatrice Pinci, Karmele Valencia, Belen Palencia, Benigno Barbes, Elixabet Bolanos, Arantza Azpilikueta, Marina Garcia-Cardosa, Javier Burguete, Iñaki Eguren-Santamaria, Eneko Garate-Soraluze, Pedro Berraondo, Jose L. Perez-Gracia, Carlos E. de Andrea, Maria E. Rodriguez-Ruiz
Purpose: Cancer patients frequently undergo radiotherapy in their clinical management with unintended irradiation of blood vessels and copiously irrigated organs in which polymorphonuclear leukocytes circulate. Following the observation that such low doses of ionizing radiation are able to induce neutrophils to extrude neutrophil extracellular traps (NETs), we have investigated the mechanisms, consequences
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Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Shifeng Lian, Chenyu Lu, Fugui Li, Xia Yu, Limei Ai, Biao-Hua Wu, Xueyi Gong, Wenjing Zhou, Xuejun Liang, Jiyun Zhan, Yong Yuan, Fang Fang, Zhiwei Liu, Mingfang Ji, Zongli Zheng
Purpose: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history. Methods: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited
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Facts and hopes on cancer immunotherapy for small cell lung cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Jon Zugazagoitia, Handerson Osma, Javier Baena, Álvaro C. Ucero, Luis Paz-Ares
Platinum-based chemotherapy plus PD-1 axis blockade is the standard of care in the front-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Despite the robust and consistent increase of long-term survival with PD-1 axis inhibition, the magnitude of the benefit from immunotherapy appears lower as compared to other solid tumors. Several immune evasive mechanisms have been shown to be
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Maintenance pembrolizumab therapy in patients with metastatic HER2-negative breast cancer with prior response to chemotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Toshiaki Iwase, Evan N. Cohen, Hui Gao, Angela Alexander, Megumi Kai, Vivian Chiv, Xiaoping Wang, Savitri Krishnamurthy, Diane Liu, Yu Shen, Kumiko Kida, Alexandre Reuben, Rachel Layman, David Ramirez, Debu Tripathy, Stacy L. Moulder, Clinton Yam, Vicente Valero, Bora Lim, James M. Reuben, Naoto T. Ueno
Purpose: Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer
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Spatially preserved multi-region transcriptomic subtyping and biomarkers of chemoimmunotherapy outcome in extensive-stage small cell lung cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Melina Peressini, Rosario Garcia-Campelo, Bartomeu Massuti, Cristina Marti, Manuel Cobo, Vanesa Gutiérrez, Manuel Dómine, Jose Fuentes, Margarita Majem, Javier de Castro, Juan Felipe Cordoba, Maria Pilar Diz, Dolores Isla, Emilio Esteban, Enric Carcereny, Laia Vila, Alberto Moreno-Vega, Silverio Ros, Amaia Moreno, Francisco Javier Garcia, Gerardo Huidobro, Carlos Aguado, Victor Cebey-Lopez, Javier
Background: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. Patients and methods: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm
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Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity from a Phase I Study of Simlukafusp Alfa (FAP-IL2v) in Advanced/Metastatic Solid Tumors Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Neeltje Steeghs, Carlos Gomez-Roca, Kristoffer S. Rohrberg, Morten Mau-Sørensen, Debbie Robbrecht, Josep Tabernero, Samreen Ahmed, Maria E. Rodriguez-Ruiz, Caroline Ardeshir, Daniela Schmid, Nassim Sleiman, Carl Watson, Hanna Piper-Lepoutre, David Dejardin, Stefan Evers, Christophe Boetsch, Jehad Charo, Volker Teichgräber, Ignacio Melero
Purpose: Simlukafusp alfa (FAP-IL2v), a tumor-targeted immunocytokine, comprising an interleukin-2 variant moiety with abolished CD25 binding fused to human immunoglobulin G1, is directed against fibroblast activation protein-α. This phase I, open-label, multicenter, dose-escalation and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of
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Efficacy of pembrolizumab and biomarker analysis in patients with WGS-based intermediate to high tumor mutational load: results from the Drug Rediscovery Protocol Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Birgit S. Geurts, Laurien J. Zeverijn, Lindsay V.M. Leek, Jade M. van Berge Henegouwen, Louisa R. Hoes, Hanneke van der Wijngaart, Vincent van der Noort, Joris van de Haar, Annemiek van Ommen-Nijhof, Marleen Kok, Paul Roepman, Anne M.L. Jansen, Wendy W.J. de Leng, Maja J. A. de Jonge, Ann Hoeben, Carla M.L. van Herpen, Hans M. Westgeest, Lodewyk F.A. Wessels, Henk M.W. Verheul, Hans Gelderblom, Emile
Purpose: To evaluate efficacy of pembrolizumab across multiple cancer types harboring different levels of Whole-Genome Sequencing (WGS)-based tumor mutational load (TML; total of non-synonymous mutations across the genome) in patients included in the Drug Rediscovery Protocol (NCT02925234). Patients and methods: Patients with solid, treatment-refractory, microsatellite-stable tumors were enrolled in
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Overcoming osimertinib resistance with AKT inhibition in EGFRm-driven Non-Small-Cell-Lung-Cancer with PIK3CA/PTEN alterations Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Ursula Grazini, Aleksandra Markovets, Lucy Ireland, Daniel O'Neill, Benjamin Phillips, Man Xu, Matthias Pfeifer, Tereza Vaclova, Matthew J. Martin, Ludovic Bigot, Luc Friboulet, Ryan Hartmaier, Maria Emanuela Cuomo, Simon T. Barry, Paul D. Smith, Nicolas Floc'h
Purpose: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) indicated for the treatment of EGFR mutated (EGFRm)-driven lung adenocarcinomas. Osimertinib significantly improves progression-free survival in first-line treated patients with EGFRm advanced NSCLC. Despite the durable disease control, the majority of patients receiving osimertinib eventually develop disease
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A cohort study of CNS tumors in Multiple Endocrine Neoplasia Type 1 Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Thomas Graillon, Pauline Romanet, Clara Camilla, Camille Gelin, Romain Appay, Catherine Roche, Arnaud Lagarde, Grégory Mougel, Kaissar Farah, Maëlle Le Bras, Julien Engelhardt, Michel Kalamarides, Matthieu Peyre, Aymeric Amelot, Evelyne Emery, Elsa Magro, Helene Cebula, Rabih Aboukais, Catherine Bauters, Emmanuel Jouanneau, Moncef Berhouma, Thomas Cuny, Henry Dufour, Hugues Loiseau, Dominique Figarella-Branger
Purpose: Multiple Endocrine Neoplasia Type-1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Hereby, we aimed to describe the frequency, the incidence and specific clinical and histological features of CNS tumors in the MEN1 population (except pituitary tumors). Experimental design: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990
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Diffuse pleural mesotheliomas with genomic near-haploidization: a newly recognized subset with distinct clinical, histologic, and molecular features Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Soo-Ryum Yang, Gowtham Jayakumaran, Jamal Benhamida, Christopher A. Febres Aldana, Rachel Fanaroff, Jason Chang, Erika Gedvilaite, Liliana B. Villafania, Jennifer L. Sauter, Michael Offin, Marjorie G. Zauderer, Marc Ladanyi
Purpose: Diffuse pleural mesotheliomas (DPMs) with genomic near-haploidization (GNH) represent a novel subtype first recognized by the TCGA project; however, its clinicopathologic and molecular features remain poorly defined. Experimental design: We analyzed clinical genomic profiling data from 290 patients with DPM using the MSK-IMPACT assay. Allele-specific copy number analysis was performed using
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Mutation Patterns Predict Drug Sensitivity in Acute Myeloid Leukemia Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-15 Guangrong Qin, Jin Dai, Sylvia Chien, Timothy J. Martins, Brenda Loera, Quy H. Nguyen, Melanie L. Oakes, Bahar Tercan, Boris Aguilar, Lauren Hagen, Jeannine McCune, Richard Gelinas, Raymond J. Monnat, Ilya Shmulevich, Pamela S. Becker
Purpose: The inherent genetic heterogeneity of acute myeloid leukemia (AML) has challenged the development of precise and effective therapies. The objective of this study was to elucidate the genomic basis of drug resistance or sensitivity, identify signatures for drug response prediction, and provide resources to the research community. Experimental Design: We performed targeted sequencing, high-throughput
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A Real-world Toxicity Atlas Shows that Adverse Events of Combination Therapies Commonly Result in Additive Interactions Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-10 Asli Küçükosmanoglu, Silvia Scoarta, Megan Houweling, Nicoleta Spinu, Thomas Wijnands, Niek Geerdink, Carolien Meskers, Georgi K. Kanev, Bert Kiewiet, Mathilde Kouwenhoven, David Noske, Tom Wurdinger, Marianne Pouwer, Mark Wolff, Bart A. Westerman
Purpose: Combination therapies are a promising approach for improving cancer treatment, but it is challenging to predict their resulting adverse events in a real-world setting. Experimental Design: We provide here a proof-of-concept study using 15 million patient records from the FDA Adverse Event Reporting System (FAERS). Complex adverse event frequencies of drugs or their combinations were visualized
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Preclinical Development of CAR T Cells with Antigen-Inducible IL18 Enforcement to Treat GD2-Positive Solid Cancers Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Lena Fischer-Riepe, Sareetha Kailayangiri, Katharina Zimmermann, Rita Pfeifer, Michael Aigner, Bianca Altvater, Sascha Kretschmann, Simon Völkl, Jordan Hartley, Celine Dreger, Katja Petry, Andreas Bosio, Angelika von Döllen, Wolfgang Hartmann, Holger Lode, Dennis Görlich, Andreas Mackensen, Melanie Jungblut, Axel Schambach, Hinrich Abken, Claudia Rossig
Purpose: Cytokine-engineering of chimeric antigen receptor-redirected T cells (CAR T cells) is a promising principle to overcome the limited activity of canonical CAR T cells against solid cancers. Experimental Design: We developed an investigational medicinal product, GD2IL18CART, consisting of CAR T cells directed against ganglioside GD2 with CAR-inducible IL18 to enhance their activation response
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Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Hyung-Joo Oh, Suk-Chul Bae, In-Jae Oh, Cheol-Kyu Park, Kyoung-Mi Jung, Da-Mi Kim, Jung-Won Lee, Chang Kyun Kang, Il Yeong Park, Young-Chul Kim
Purpose: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR–tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer
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Preclinical efficacy of a PSMA-targeted actinium-225 conjugate (225Ac-macropa-pelgifatamab) - a targeted alpha therapy for prostate cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Christoph A. Schatz, Sabine Zitzmann-Kolbe, Ingrid Moen, Monika Klotz, Shankari Nair, Stefan Stargard, Roger M. Bjerke, Katrine Wickstrøm Biseth, Yuan Zeng. Feng, Bård Indrevoll, Véronique Cruciani, Jenny Karlsson, Bernard Haendler, Carsten H. Nielsen, Maria Z. Alfsen, Stefanie Hammer, Hartwig Hennekes, Alan Cuthbertson, Urs B. Hagemann, Aasmund Larsen
Purpose: Initially, prostate cancer responds to hormone therapy but eventually resistance develops. Beta emitter-based PSMA (prostate-specific membrane antigen)-targeted radionuclide therapy is approved for the treatment of metastatic castration-resistant prostate cancer. Here we introduce a targeted alpha therapy (TAT) consisting of the PSMA antibody pelgifatamab covalently linked to a macropa chelator
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CB307: A Dual Targeting Costimulatory Humabody VH Therapeutic for Treating PSMA-Positive Tumors Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Sophie Archer, Phillip M. Brailey, Minjung Song, Phillip D. Bartlett, Ines Figueiredo, Bora Gurel, Christina Guo, Verena Brucklacher-Waldert, H. Lorraine Thompson, Jude Akinwale, Samantha E. Boyle, Christine Rossant, Neil R. Birkett, Julia Pizzey, Mark Maginn, James Legg, Richard Williams, Colette M. Johnston, Philip Bland-Ward, Johann S. de Bono, Andrew J. Pierce
Purpose: CD137 is a T- and NK-cell costimulatory receptor involved in consolidating immunologic responses. The potent CD137 agonist urelumab has shown clinical promise as a cancer immunotherapeutic but development has been hampered by on-target off-tumor toxicities. A CD137 agonist targeted to the prostate-specific membrane antigen (PSMA), frequently and highly expressed on castration-resistant metastatic
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Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147) Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Sangini S. Sheth, Ji Eun Oh, Stefania Bellone, Eric R. Siegel, Michelle Greenman, Levent Mutlu, Blair McNamara, Shefali Pathy, Mitchell Clark, Masoud Azodi, Gary Altwerger, Vaagn Andikyan, Gloria Huang, Elena Ratner, Daniel J. Kim, Akiko Iwasaki, Angelique W. Levi, Natalia Buza, Pei Hui, Sean Flaherty, Peter E. Schwartz, Alessandro D. Santin
Purpose: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. Patients and Methods: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with
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Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Farah Ballout, Heng Lu, Nadeem Bhat, Lei Chen, Dunfa Peng, Zheng Chen, Steven Chen, Xiaodian Sun, Silvia Giordano, Simona Corso, Alexander Zaika, Oliver McDonald, Alan S. Livingstone, Wael El-Rifai
Purpose: TGFβ signaling is implicated in the progression of most cancers, including esophageal adenocarcinoma (EAC). Emerging evidence indicates that TGFβ signaling is a key factor in the development of resistance toward cancer therapy. Experimental Design: In this study, we developed patient-derived organoids and patient-derived xenograft models of EAC and performed bioinformatics analysis combined
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Impact of Circulating Tumor Cell–Expressed Prostate-Specific Membrane Antigen and Prostate-Specific Antigen Transcripts in Different Stages of Prostate Cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-08 Hyungseok Cho, Seok-Soo Byun, Nak-Hoon Son, Jae Il Chung, Won Ik Seo, Chan Ho Lee, Todd M. Morgan, Ki-Ho Han, Jae-Seung Chung
Purpose: Prostate-specific membrane antigen (PSMA)–based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)–based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. Experimental Design: We prospectively enrolled 21 healthy individuals
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Stabilizing tumor resident mast cells restores T cell infiltration and sensitizes sarcomas to PD-L1 inhibition Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-05 Myrofora Panagi, Fotios Mpekris, Chrysovalantis Voutouri, Andreas G. Hadjigeorgiou, Chloe Symeonidou, Eleni Porfyriou, Christina Michael, Andreas Stylianou, John D. Martin, Horacio Cabral, Anastasia Constantinidou, Triantafyllos Stylianopoulos
Purpose: To explore the cellular crosstalk of tumor resident mast cells (MCs) in controlling the activity of cancer-associated fibroblasts (CAFs) to overcome TME abnormalities, enhancing the efficacy of immune checkpoint inhibitors (ICIs) in sarcoma. Experimental Design: We used a coculture system followed by further validation in mouse models of fibrosarcoma and osteosarcoma with or without administration
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IRX4204 Induces Senescence and Cell Death in HER2-positive Breast Cancer and Synergizes with Anti-HER2 Therapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-05 Cassandra L. Moyer, Amanda Lanier, Jing Qian, Darian Coleman, Jamal Hill, Vidyasagar Vuligonda, Martin E. Sanders, Abhijit Mazumdar, Powel H. Brown
Purpose: Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well-tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response
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Safety and preliminary efficacy of pembrolizumab following trans-arterial chemoembolization for hepatocellular carcinoma: the PETAL phase Ib study. Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-05 David J. Pinato, Antonio D'Alessio, Claudia Angela Maria. Fulgenzi, Alexandra Emilia Schlaak, Ciro Celsa, Saskia Killmer, Jesus Miguens. Blanco, Caroline Ward, Charalampos-Vlasios Stikas, Mark R. Openshaw, Nicole Acuti, Georgios Nteliopoulos, Cristina Balcells, Hector C. Keun, Robert D. Goldin, Paul J. Ross, Alessio Cortellini, Robert Thomas, Anna Mary. Young, Nathan Danckert, Paul Tait, Julian R.
Background. TACE may prime adaptive immunity and enhance immunotherapy efficacy. PETAL evaluated safety, preliminary activity of TACE plus pembrolizumab and explored mechanisms of efficacy. Methods. Patients with liver-confined HCC were planned to receive up to 2 rounds of TACE followed by pembrolizumab 200 mg every 21 days commencing 30-days post-TACE until disease progression or unacceptable toxicity
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New means and challenges in the targeting of BTK Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-05 Vindhya Nawaratne, Anya K. Sondhi, Omar Abdel-Wahab, Justin Taylor
Bruton’s tyrosine kinase (BTK) is central to the survival of malignant and normal B-lymphocytes and has been a crucial therapeutic target of several generations of kinase inhibitors and newly developed degraders. These new means for targeting BTK have added additional agents to the armamentarium for battling cancers dependent on B-cell receptor (BCR) signaling, including chronic lymphocytic leukemia
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Co-occurring EGFR p.E709X mutation Mediates Primary Resistance to the Third-generation EGFR-TKIs in EGFR p.G719X-mutant Patients with Advanced NSCLC Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-05 Lanlan Pang, Yihua Huang, Weitao Zhuang, Yaxiong Zhang, Jun Liao, Yue Hao, Feng Hao, Guoqian Wang, Ze-xin Chase. Chen, Yu Zhu, Mengzhen Li, Zhengbo Song, Bo Peng. Deng, Jing Li, Li Zhang, Wenfeng Fang
Purpose: Current NCCN guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X mutant patients, it is unclear which regimen is the preferred treatment option. Experimental Design: A large cohort of 4228
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Applications and opportunities for immune cell CAR engineering in comparative oncology Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-04 Antonia Rotolo, Matthew J. Atherton
Chimeric antigen receptor (CAR) T adoptive cell therapy has transformed the treatment of human hematologic malignancies. However, its application for the treatment of solid tumors remains challenging. An exciting avenue for advancing this field lies in the use of pet dogs, in which cancers that recapitulate the biology, immunological features, and clinical course of human malignancies arise spontaneously
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Update on cancer predisposition syndromes and surveillance guidelines for childhood brain tumors Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-04 Jordan R. Hansford, Anirban Das, Rose B. McGee, Yoshiko Nakano, Jack Brzezinski, Sarah R. Scollon, Surya P. Rednam, Jaclyn Schienda, Orli Michaeli, Sun Young Kim, Mary-Louise C. Greer, Rosanna Weksberg, Douglas R. Stewart, William D. Foulkes, Uri Tabori, Kristian W. Pajtler, Stefan M. Pfister, Garrett M. Brodeur, Junne Kamihara
Tumors of the central nervous system (CNS) comprise the second most common group of neoplasms in childhood. The incidence of germline predisposition among children with brain tumors continues to grow as our knowledge on disease aetiology increases. Some children with brain tumors may present with non-malignant phenotypic features of specific syndromes (e.g. nevoid basal cell carcinoma syndrome, neurofibromatosis
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Comprehensive Genomic Profiling Alters Clinical Diagnoses in a Significant Fraction of Tumors Suspicious of Sarcoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-04 Ingegerd Öfverholm*, Karin Wallander*, Cecilia Haglund, Venkatesh Chellappa, Johan Wejde, Anna Gellerbring, Valtteri Wirta, Annick Renevey, Eva Caceres, Panagiotis Tsagkozis, Markus Mayrhofer, Andri Papakonstantinou, Christina Linder-Stragliotto, Robert Bränström, Olle Larsson, Johan Lindberg, Yingbo Lin, Felix Haglund de Flon
Purpose: Tumor classification is a key component in personalized cancer care. For soft tissue and bone tumors, this classification is currently based primarily on morphology assessment and immunohistochemical staining. However, these standard-of-care methods can pose challenges for pathologists. We therefore assessed how whole-genome and whole-transcriptome sequencing (WGTS) impacted tumor classification
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Statins Do Not Significantly Affect Oxidative Nitrosative Stress Biomarkers in the PREVENT Randomized Clinical Trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-04 Igor Makhlin, Biniyam G. Demissei, Ralph D’Agostino, W. Greg. Hundley, Camelia Baleanu-Gogonea, Nicholas S. Wilcox, Anna Chen, Amanda M. Smith, Nathaniel Sean O’Connell, James Januzzi, Glenn J. Lesser, Marielle Scherrer-Crosbie, Borja Ibáñez, W. H. Wilson Tang, Bonnie Ky
Purpose: Preventing Anthracycline Cardiovascular Toxicity with Statins (PREVENT) (NCT01988571) randomized breast cancer or lymphoma patients receiving anthracyclines to atorvastatin 40 mg daily or placebo. We evaluated the effects of atorvastatin on oxidative and nitrosative stress biomarkers, and explored whether these biomarkers could explain the lack of effect of atorvastatin on LVEF in PREVENT
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KLRG1, Another Opportunity for a Breakthrough in MTCL Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-03 Gaurav Varma, Catherine S. Diefenbach
Outcomes in mature T-cell lymphomas remain poor, with previous attempts at developing monoclonal antibodies (mAb) compromised by limited efficacy and significant immunocompromise. Anti-killer cell lectin-like receptor G1 mAbs may have greater selectivity and specificity for malignant T-cells and avoid the toxicity concerns with previous agents.
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The VEGF-Hypoxia Signature is Upregulated in Basal like Breast Tumors from Women of African Ancestry and Associated with Poor Outcomes in Breast Cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-02 Yoo Jane Han, Siyao Liu, Ashley Hardeman, Padma Sheila. Rajagopal, Jeffrey Mueller, Galina Khramtsova, Ayodele Sanni, Mustapha A. Ajani, Wendy Clayton, Ian W. Hurley, Toshio F. Yoshimatsu, Yonglan Zheng, Joel Parker, Charles M. Perou, Olufunmilayo I. Olopade
Purpose: Black women experience the highest breast cancer mortality rate compared to women of other racial/ethnic groups. To gain a deeper understanding of breast cancer heterogeneity across diverse populations, we examined a VEGF-hypoxia gene expression signature in breast tumors from women of diverse ancestry. Experimental Design: We developed a NanoString nCounter gene expression panel and applied
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Clinical challenges of consensus molecular subtype CMS4 colon cancer in the era of precision medicine Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-02 Sophie Mouillet-Richard, Antoine Cazelles, Marine Sroussi, Claire Gallois, Julien Taieb, Pierre Laurent-Puig
Over the past decade, our understanding of the diversity of colorectal cancer (CRC) has expanded significantly, raising hopes of tailoring treatments more precisely for individual patients. A key achievement in this direction was the establishment of the consensus molecular classification, particularly identifying the challenging consensus molecular subtype (CMS) CMS4 associated with poor prognosis
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Solid organ transplant recipients exhibit more TET2-mutant clonal hematopoiesis of indeterminate potential not driven by increased transplantation risk Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-29 Alexander J. Silver, Caitlyn Vlasschaert, Taralynn Mack, Brian Sharber, Yaomin Xu, Alexander G. Bick, C. Wright. Pinson, Michael R. Savona
Purpose: Solid organ transplant recipients comprise a unique population of immunosuppressed patients with increased risk of malignancy, including hematologic neoplasms. Clonal hematopoiesis of indeterminate potential (CHIP) represents a known risk factor for hematologic malignancy and this study describes the prevalence and patterns of CHIP mutations across several types of solid organ transplants
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GD2-targeting CAR T-cell therapy for patients with GD2+ medulloblastoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-29 Roselia Ciccone, Concetta Quintarelli, Antonio Camera, Michele Pezzella, Simona Caruso, Simona Manni, Alessio Ottaviani, Marika Guercio, Francesca Del Bufalo, Maria Cecilia Quadraccia, Domenico Orlando, Stefano Di Cecca, Matilde Sinibaldi, Mariasole Aurigemma, Laura Iaffaldano, Andrea Sarcinelli, Maria Luisa D' Amore, Manuela Ceccarelli, Francesca Nazio, Veronica Marabitti, Ezio Giorda, Marco Pezzullo
Purpose: Medulloblastoma (MB), the most common childhood malignant brain tumor, has a poor prognosis in about 30% of patients. The current standard of care, which includes surgery, radiation and chemotherapy, is often responsible for cognitive, neurologic and endocrine side effects. We investigated whether chimeric antigen receptor (CAR) T-cells directed towards the disialoganglioside GD2 can represent
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Safety, efficacy, and biological data of T cell-enabling oncolytic adenovirus TILT-123 in advanced solid cancers from the TUNIMO monotherapy phase I trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-28 Santeri A. Pakola, Katriina J. Peltola, James H.A. Clubb, Elise Jirovec, Lyna Haybout, Tatiana V. Kudling, Tuomo Alanko, Riitta Korpisaari, Susanna Juteau, Marjut Jaakkola, Jorma Sormunen, Jukka Kemppainen, Annabrita Hemmes, Teijo Pellinen, Mirte van der Heijden, Dafne C.A. Quixabeira, Claudia Kistler, Suvi Sorsa, Riikka Havunen, Joao M. Santos, Victor Cervera-Carrascon, Akseli E. Hemminki
Purpose: TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with tumor necrosis factor alpha and interleukin-2, designed to induce T-cell infiltration and cytotoxicity in solid tumors. Patients and Methods: TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose escalation trial designed to assess safety of TILT-123 in advanced solid cancers refractory to standard therapy
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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