Article
Oncology
Daniel H. Kwon, Jonathan Chou, Steven M. Yip, Melissa A. Reimers, Li Zhang, Francis Wright, Mallika S. Dhawan, Hala T. Borno, Arpita Desai, Rahul R. Aggarwal, Alexander W. Wyatt, Eric J. Small, Ajjai S. Alva, Kim N. Chi, Felix Y. Feng, Vadim S. Koshkin
Summary: DDRm mutations are common in mCRPC patients. BRCA1/2 mutations are associated with superior responses to standard therapies, while ATM or CDK12 mutations are linked to inferior responses. Specific DDRm type and first-line treatments do not independently predict OS. Carboplatin-based chemotherapy after first-line treatment is correlated with the longest OS.
Article
Biochemistry & Molecular Biology
Thais Maloberti, Antonio De Leo, Sara Coluccelli, Viviana Sanza, Elisa Gruppioni, Annalisa Altimari, Stefano Zagnoni, Francesca Giunchi, Francesco Vasuri, Michelangelo Fiorentino, Veronica Mollica, Simona Ferrari, Sara Miccoli, Michela Visani, Daniela Turchetti, Francesco Massari, Giovanni Tallini, Dario de Biase
Summary: Despite advances in therapy, metastatic CRPC remains lethal. This study aimed to verify the effectiveness of a panel in analyzing mCRPC and mutations in BRCA1/BRCA2 and HRR genes. 50 mCRPC cases were analyzed using a multi-gene next-generation sequencing panel, and mutations were found in 46.0% of cases, with BRCA2 being the most commonly mutated gene. The panel and clinical algorithm are now used for managing mCRPC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Ravi A. Madan, Fatima H. Karzai, Munjid Al Harthy, Daniel P. Petrylak, Joseph W. Kim, Philip M. Arlen, Inger Rosner, Marc R. Theoret, Lisa Cordes, Marijo Bilusic, Cody J. Peer, Nancy A. Dawson, Anna Couvillon, Amy Hankin, Moniquea Williams, Guin Chun, Helen Owens, Jennifer L. Marte, Min-Jung Lee, Yusuke Tomita, Akira Yuno, Jane B. Trepel, Sunmin Lee, Seth M. Steinberg, James L. Gulley, William D. Figg, William L. Dahut
Summary: The study evaluated the safety and efficacy of cabozantinib combined with docetaxel in mCRPC patients. Cabozantinib was found to be safely added to docetaxel treatment with potential enhanced efficacy. However, due to limited patient accrual, the phase 2 study was terminated early.
Article
Chemistry, Medicinal
Yujie Huang, You Zhai, Meijia Wu, Chengdong Chang, Jindan Luo, Dongsheng Hong, Qingwei Zhao, Yao Dai, Jian Liu
Summary: This study investigated the role of mTORC2 signaling in docetaxel-resistant prostate cells to find potential methods for clinical treatment. The expression of mTORC2 is crucial for docetaxel drug resistance in prostate cells. The mTORC1/2 inhibitor AZD8055 disrupts mTORC2 kinase activity more significantly than the mTORC1 inhibitor Rapamycin, leading to decreased docetaxel-mediated resistance. Therefore, reversing docetaxel resistance may become a therapeutic option for the treatment of metastatic castration-resistant prostate cancer patients.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Biology
Kevin J. Tu, Sanjit K. Roy, Zachery Keepers, Manas R. Gartia, Hem D. Shukla, Nrusingh C. Biswal
Summary: The study investigates the effectiveness and molecular characteristics of the combination therapy of Docetaxel (DXL) and radiation in vitro. The results suggest that DXL sensitizes castration-resistant prostate cancer (CRPC) cells to radiation by downregulating CAV-1.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)
Article
Oncology
Yuting Shan, Yingbo Huang, Adam M. Lee, Joshua Mentzer, Alexander Ling, R. Stephanie Huang
Summary: This study suggests that GAS5 expression may serve as a predictive biomarker for docetaxel response in castration-resistant prostate cancer (CRPC), although the exact mechanism behind this correlation remains to be elucidated. The findings also demonstrate that the change in GAS5 expression does not directly affect docetaxel response, and there is no significant relationship between GAS5 and ABCB1 expression that impacts docetaxel sensitivity.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Wei Ning, Pengkang Chang, Ji Zheng, Fan He
Summary: This case report highlights the potential effectiveness and safety of a second docetaxel rechallenge as a later-line treatment strategy for patients with mCRPC who are concerned about the high costs of multigene molecular testing and PARP inhibitors, as well as repeated prostate needle biopsy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Atefeh Deris, Mahdi Sohrabi-Haghighat
Summary: Patients with mCRPC are classified into three groups based on their response to Abiraterone treatment: best responder, responder, and non-responder. Drug-resistant cells may hinder successful outcomes in the latter two groups. To overcome this challenge, a combination of Docetaxel and Abiraterone is proposed to control both the overall cancer cell population and the drug-resistant subpopulation. Evolutionary Game Theory (EGT) is used as a mathematical modeling approach to study the competition and evolution of mCRPC cancer phenotypes.
Article
Oncology
Edoardo Francini, Fang-Shu Ou, Justin Rhoades, Eric G. Wolfe, Edward P. O'Connor, Gavin Ha, Gregory Gydush, Kaitlin M. Kelleher, Rupal S. Bhatt, Steven P. Balk, Christopher J. Sweeney, Viktor A. Adalsteinsson, Mary-Ellen Taplin, Atish D. Choudhury
Summary: This study aimed to evaluate the association between ABC transporter gene ABCB1 amplification and primary resistance to docetaxel or cabazitaxel in mCRPC patients using sparse whole genome sequencing, but no significant correlation was found. Future studies with larger sample sizes including ABCB1 amplification and a suite of putative biomarkers are needed to draw definitive conclusions.
Article
Oncology
Xiang Cai, Xi Duan, Tielong Tang, Shu Cui, Tao Wu
Summary: This study investigated the mechanism of JMJD2A in regulating cytoskeleton remodeling in docetaxel-resistant castration-resistant prostate cancer cells. The results showed that JMJD2A regulates cytoskeleton remodeling through the miR-34a/STMN1/beta 3-Tubulin axis. Overexpression of miR-34a resulted in downregulation of STMN1 and upregulation of beta 3-Tubulin, leading to disruption of the microtubule network, inhibition of cancer cell proliferation, cell cycle arrest, and increased apoptosis.
Article
Oncology
Johann S. de Bono, Niven Mehra, Giorgio Scagliotti, Elena Castro, Tanya Dorff, Adam Stirling, Arnulf Stenzl, Mark T. Fleming, Celestia S. Higano, Fred Saad, Consuelo Buttigliero, Inge M. van Oort, A. Douglas Laird, Marielena Mata, Hsiang-Chun Chen, Cynthia G. Healy, Akos Czibere, Karim Fizazi
Summary: Talazoparib demonstrated durable antitumour activity in advanced metastatic castration-resistant prostate cancers with DDR-HRR gene alterations, supporting further investigation in larger, randomised clinical trials.
Article
Urology & Nephrology
Kristine Kreis, Dirk Horenkamp-Sonntag, Udo Schneider, Jan Zeidler, Gerd Glaeske, Lothar Weissbach
Summary: This study examined real-world haematological toxicity, overall survival, and treatment characteristics of docetaxel and cabazitaxel chemotherapy in mCRPC patients. The findings suggest that cabazitaxel treatment poses higher risk of haematological toxicities and shorter survival time, emphasizing the importance of strict indications when using cabazitaxel in mCRPC patients.
Article
Andrology
Georg Schaefer, Nikola Bednarova, Axel Heidenreich, Helmut Klocker, Isabel Heidegger
Summary: The study found that KDM5D is significantly overexpressed in patients who respond to chemotherapy, indicating that KDM5D may be a promising new biomarker for predicting treatment response in mCRPC.
TRANSLATIONAL ANDROLOGY AND UROLOGY
(2021)
Article
Oncology
Vincenza Conteduca, Daniel Wetterskog, Elena Castro, Emanuela Scarpi, Nuria Romero-Laorden, Giorgia Gurioli, Anuradha Jayaram, Cristian Lolli, Giuseppe Schepisi, Anna Wingate, Chiara Casadei, Rebeca Lozano, Nicole Brighi, Isabel M. Aragon, Mercedes Marin-Aguilera, Enrique Gonzalez-Billalabeitia, Begona Mellado, David Olmos, Gerhardt Attard, Ugo De Giorgi
Summary: The relevance of plasma AR in the overall management of CRPC patients receiving different docetaxel doses is currently unknown.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Tomas Januskevicius, Rasa Sabaliauskaite, Daiva Dabkeviciene, Ieva Vaicekauskaite, Ilona Kulikiene, Agne Sestokaite, Asta Vidrinskaite, Arnas Bakavicius, Feliksas Jankevicius, Albertas Ulys, Sonata Jarmalaite
Summary: This study aimed to correlate germline and/or somatic DNA damage response (DDR) mutations in blood and urine samples from metastatic castration-resistant prostate cancer (mCRPC) patients with response to systemic treatment and survival outcomes. The results showed that DDR mutations were detected in both urine and blood samples, and these mutations were associated with shorter progression-free survival (PFS) in response to conventional androgen deprivation therapy and first-line mCRPC therapy with abiraterone acetate. However, DDR mutation status was predictive for the beneficial effect of second-line abiraterone acetate after previous taxane-based chemotherapy.
Article
Oncology
Joshua Z. Drago, Mithat Gonen, Gita Thanarajasingam, Chana A. Sacks, Michael J. Morris, Philip W. Kantoff, Konrad H. Stopsack
Summary: This study evaluated the adverse event (AE) profiles of three advanced prostate cancer drugs and found significant differences in AE risks in the placebo arms and levels of uncertainty between trials. The research highlights considerable opportunities for improvement in how AE data are collected, analyzed, and interpreted in oncology trials.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Oncology
Michael J. Morris, Steven P. Rowe, Michael A. Gorin, Lawrence Saperstein, Frederic Pouliot, David Josephson, Jeffrey Y. C. Wong, Austin R. Pantel, Steve Y. Cho, Kenneth L. Gage, Morand Piert, Andrei Iagaru, Janet H. Pollard, Vivien Wong, Jessica Jensen, Tess Lin, Nancy Stambler, Peter R. Carroll, Barry A. Siegel
Summary: F-18-DCFPyL-PET/CT demonstrated good localization performance in patients with BCR, providing meaningful and actionable information that led to a change in management for 63.9% of patients.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Philippe Aftimos, Mafalda Oliveira, Alexandre Irrthum, Debora Fumagalli, Christos Sotiriou, Einav Nili Gal-Yam, Mark E. Robson, Justin Ndozeng, Angelo Di Leo, Eva M. Ciruelos, Evandro de Azambuja, Giuseppe Viale, Elsemieke D. Scheepers, Giuseppe Curigliano, Judith M. Bliss, Jorge S. Reis-Filho, Marco Colleoni, Marija Balic, Fatima Cardoso, Joan Albanell, Caroline Duhem, Sandrine Marreaud, Dario Romagnoli, Beatriz Rojas, Andrea Gombos, Hans Wildiers, Angel Guerrero-Zotano, Peter Hall, Andrea Bonetti, Karolina Fs Larsson, Martina Degiorgis, Silvia Khodaverdi, Richard Greil, Asgerdur Sverrisdottir, Marta Paoli, Ethel Seyll, Sibylle Loibl, Barbro Linderholm, Gabriele Zoppoli, Nancy E. Davidson, Oskar Th Johannsson, Philippe L. Bedard, Sherene Loi, Susan Knox, David A. Cameron, Nadia Harbeck, Maite Lasa Montoya, Mariana Brandao, Andrea Vingiani, Carmela Caballero, Florentine S. Hilbers, Lucy R. Yates, Matteo Benelli, David Venet, Martine J. Piccart
Summary: The AURORA program conducted genomic and transcriptomic analyses on matched primary and metastatic samples from 381 breast cancer patients, identifying genomic alterations enriched in metastases and prognostic biomarkers. Over half of the patients had ESCAT tier I/II alterations detected.
Article
Oncology
Willard Wong, Edi Brogi, Jorge S. Reis-Filho, George Plitas, Mark Robson, Larry Norton, Monica Morrow, Hannah Y. Wen
Summary: The study evaluated the response to neoadjuvant chemotherapy in 44 patients with metaplastic breast carcinoma, finding that only 2% achieved a pathologic complete response, indicating poor response to NAC in most MpBC patients.
Article
Oncology
Konrad H. Stopsack, Subhiksha Nandakumar, Kanika Arora, Bastien Nguyen, Samantha E. Vasselman, Barbara Nweji, Sean M. McBride, Michael J. Morris, Dana E. Rathkopf, Susan F. Slovin, Daniel C. Danila, Karen A. Autio, Howard Scher, Lorelei A. Mucci, David B. Solit, Mithat Gonen, Yu Chen, Michael F. Berger, Nikolaus Schultz, Wassim Abida, Philip W. Kantoff
Summary: The study found that, even after adjusting for clinical characteristics, there were still differences in tumor genomics between races, with tumors from Black men carrying fewer PTEN mutations and more AR alterations. Therapies targeting alterations more common in racial minorities are needed.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Aseem Anand, Glenn Heller, Joseph Fox, Daniel C. Danila, Anders Bjartell, Lars Edenbrandt, Steven M. Larson, Howard Scher, Michael J. Morris
Summary: The study aimed to quantify the increase in tumor burden represented by prostate cancer working group progression criteria and determine the most optimal interval increase associated with overall survival. The results showed that an absolute increase of 0.6 or more in aBSI from the first follow-up scan resulted in the highest association with overall survival in patients with metastatic castration-resistant prostate cancer.
CLINICAL GENITOURINARY CANCER
(2022)
Article
Oncology
Aaron P. Mitchell, Akriti Mishra, Katherine S. Panageas, Allison Lipitz-Snyderman, Peter B. Bach, Michael J. Morris
Summary: This study found that more than one-quarter of patients with mCSPC who had no evidence of high osteoporotic fracture risk received BMAs in recent years, suggesting potential overuse.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Editorial Material
Oncology
Maha Hussain, Michael A. Carducci, Noel Clarke, Sarah E. Fenton, Karim Fizazi, Silke Gillessen, Heather Jacene, Michael J. Morris, Fred Saad, Oliver Sartor, Mary-Ellen Taplin, Neha Vapiwala, Scott Williams, Christopher Sweeney
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Aaron P. Mitchell, Akriti Mishra Meza, Katherine S. Panageas, Allison Lipitz-Snyderman, Azeez Farooki, Michael J. Morris
Summary: The study found that two-thirds of mCRPC patients with bone metastases received bone modifying agents (BMAs) within 180 days after initiating CDT. A greater proportion of patients without bone metastasis may warrant BMA therapy for osteoporotic fracture prevention. Some patients with bone metastasis may be able to delay BMA initiation until CRPC.
PROSTATE CANCER AND PROSTATIC DISEASES
(2023)
Article
Dermatology
Jennifer L. Hay, Erica H. Lee, Stephanie N. Christian, Elizabeth Schofield, Jada G. Hamilton, Ciyu Yang, Bobak Hedayati, Keimya Sadeghi, Mark E. Robson, Allan Halpern, Liying Zhang, Irene Orlow
Summary: This study investigated the interest and uptake of genetic testing in dermatology patients, specifically for melanocortin receptor gene (MC1R) variants. The results showed a high level of interest in MC1R genetic testing and promising outcomes, including increased family and physician communication.
JOURNAL OF SKIN CANCER
(2022)
Article
Oncology
Mark E. Robson, Seock-Ah Im, Elzbieta Senkus, Binghe Xu, Susan M. Domchek, Norikazu Masuda, Suzette Delaloge, Nadine Tung, Anne Armstrong, Mike Dymond, Anitra Fielding, Allison Allen, Pierfranco Conte
Summary: In the Phase III OlympiAD study, olaparib demonstrated a significant prolongation of progression-free survival for patients with germline BRCA-mutated metastatic breast cancer, especially in those receiving it as first-line treatment. The median overall survival for olaparib was 19.3 months, compared to 17.1 months for chemotherapy treatment of physician's choice. These results suggest a potential long-term survival benefit with olaparib.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Michael J. Morris, Glenn Heller, David W. Hillman, Olivia Bobek, Charles Ryan, Emmanuel S. Antonarakis, Alan H. Bryce, Olwen Hahn, Himisha Beltran, Andrew J. Armstrong, Lawrence Schwartz, Lionel D. Lewis, Jan H. Beumer, Brooke Langevin, Eric C. McGary, Paul T. Mehan, Amir Goldkorn, Bruce J. Roth, Han Xiao, Colleen Watt, Mary-Ellen Taplin, Susan Halabi, Eric J. Small
Summary: The purpose of this study was to determine whether the addition of abiraterone acetate and prednisone (AAP) to enzalutamide prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) in the first-line setting. The results showed that the addition of AAP did not provide a statistically significant benefit in OS compared to enzalutamide treatment alone.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Minna K. Lee, Mark E. Robson
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Multidisciplinary Sciences
Joshua A. Korsen, Julia A. Gutierrez, Kathryn M. Tully, Lukas M. Carter, Zachary Samuels, Samantha Khitrov, John T. Poirier, Charles M. Rudin, Yu Chen, Michael J. Morris, Lisa Bodei, Nagavarakishore Pillarsetty, Jason S. Lewis
Summary: This study developed and evaluated a Lu-177-labeled DLL3-targeting antibody SC16 (Lu-177-DTPA-SC16) as a treatment for NEPC. The drug showed high tumor uptake and specificity in in vivo experiments, and demonstrated dose-dependent therapeutic efficacy and safety in mouse models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Mark Robson
Summary: The Oncology Grand Rounds series provides clinical context for original reports published in the Journal, helping readers understand how to apply key study results to their own clinical practice through case presentations, review of literature, and suggested management approaches.
JOURNAL OF CLINICAL ONCOLOGY
(2021)