Article
Pharmacology & Pharmacy
Anastasia A. Sachkova, Daria V. Andreeva, Alexander S. Tikhomirov, Alexander M. Scherbakov, Diana I. Salnikova, Danila V. Sorokin, Fedor B. Bogdanov, Yulia D. Rysina, Andrey E. Shchekotikhin, Ekaterina S. Shchegravina, Alexey Yu. Fedorov
Summary: This study aimed to develop a series of c-Met-targeting cabozantinib-based PROTACs and evaluate their anti-proliferative activity and effects on c-Met. The results showed that two compounds exhibited good inhibitory activity at the nanomolar concentration and can be used as starting points for further development of cabozantinib-based PROTACs.
Article
Biochemistry & Molecular Biology
Laxminarayan Rawat, Murugabaskar Balan, Yuzuru Sasamoto, Akash Sabarwal, Soumitro Pal
Summary: In renal cell carcinoma, c-Met and Nrf2 play important roles in therapy resistance. The combination treatment of Cabozantinib and Honokiol has been found to synergistically inhibit renal cancer cell growth and promote apoptosis and autophagy-mediated cell death. This combination treatment can downregulate Rubicon, p62, and Nrf2 expression in renal cancer cells and significantly inhibit renal tumor growth in vivo.
Article
Gastroenterology & Hepatology
Yun Beom Sang, Gwangil Kim, Sohyun Hwang, Haeyoun Kang, Hong Jae Chon
Summary: We report a case of a patient with c-MET amplified hepatocellular carcinoma (HCC) who showed a dramatic response to cabozantinib despite being refractory to previous systemic therapies. The patient's HCC was well-controlled with cabozantinib treatment, even though they experienced mild adverse events. This is the first reported case of a significant response to cabozantinib in a patient with advanced HCC and c-MET amplification.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Review
Oncology
Cecile Manceau, Gaelle Fromont, Jean-Baptiste Beauval, Eric Barret, Laurent Brureau, Gilles Crehange, Charles Dariane, Gaelle Fiard, Mathieu Gauthe, Romain Mathieu, Raphaele Renard-Penna, Guilhem Roubaud, Alain Ruffion, Paul Sargos, Morgan Roupret, Guillaume Ploussard
Summary: Biomarkers have the potential to improve classification and monitoring in active surveillance for prostate cancer, allowing for more personalized prognostic assessments. While no single biomarker should dictate treatment decisions, they can each contribute as a piece of the puzzle in important decision-making processes. Further research is needed to fully understand the role of biomarkers in monitoring patient outcomes during active surveillance.
Article
Biochemistry & Molecular Biology
Shreya Kumar, Grace E. Mulia, Marxa L. Figueiredo
Summary: Combination therapy of chemotherapy and immunotherapy shows potential as a novel therapeutic strategy for treating bone-metastatic prostate cancer, with reduced chemotherapy-associated toxicity, enhanced sensitivity to immunotherapy, and improved bone quality.
FRONTIERS IN MOLECULAR BIOSCIENCES
(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
Pathology
Gemma R. Armstrong, Mohammed Ibrahim Khot, Jim P. Tiernan, Nick P. West, Sarah L. Perry, Tom Maisey, Thomas A. Hughes, David G. Jayne
Summary: The transmembrane protein c-Met is consistently overexpressed in human colorectal cancer compared to normal colorectal epithelium, showing high specificity but low sensitivity as a potential diagnostic tissue biomarker. Its expression may play a role in diagnosis and prognosis when combined with other biomarkers.
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
(2021)
Article
Oncology
Jingquan Jia, Lauren Howard, Yingmiao Liu, Mark D. Starr, John C. Brady, Donna Niedzwiecki, John H. Strickler, Andrew B. Nixon
Summary: This study identified circulating HGF and several inflammatory and angiogenic proteins as prognostic biomarkers. Furthermore, MET amplification status is associated with both baseline expression and on-treatment modulation of members of angiogenesis and TGF-beta pathway proteins.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ujjwala Karmacharya, Diwakar Guragain, Prakash Chaudhary, Jun-Goo Jee, Jung-Ae Kim, Byeong-Seon Jeong
Summary: Two novel bioisosteres of cabozantinib were synthesized, with compound 4 showing higher inhibitory and anti-proliferative activities, indicating its potential as a therapeutic candidate for hepatocellular carcinoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Aya Yamamura, Md Junayed Nayeem, Hiroyuki Muramatsu, Kogenta Nakamura, Motohiko Sato
Summary: The study revealed that the VEGFR-3 signaling pathway plays a crucial role in the proliferation, migration, and tumor growth of androgen-independent/highly metastatic prostate cancer cells, highlighting its potential as a novel therapeutic target for prostate cancer treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Virginie Firlej, Pascale Soyeux, Maya Nourieh, Eric Huet, Fannie Semprez, Yves Allory, Arturo Londono-Vallejo, Alexandre de la Taille, Francis Vacherot, Damien Destouches
Summary: Prostate cancer is the second most common cancer in men, and nucleolin, a protein involved in various cell processes, is overexpressed in PCa tissues. However, its prognostic value is still unclear. Co-expression of nine genes with NCL may have an impact on prostate cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medical Laboratory Technology
Ahmad Movahedpour, Seyyed Hossein Khatami, Neda Karami, Omid Vakili, Parisa Naeli, Zeinab Jamali, Zahra Shabaninejad, Khalil Tazik, Hamid Behrouj, Hassan Ghasemi
Summary: This article reviewed the importance and roles of exosomal ncRNAs in prostate cancer (PCa), with a focus on different miRNAs and lncRNAs found in various liquid samples that can serve as biomarkers for PCa diagnosis.
CLINICA CHIMICA ACTA
(2022)
Article
Multidisciplinary Sciences
Tsion Zewdu Minas, Julian Candia, Tiffany H. Dorsey, Francine Baker, Wei Tang, Maeve Kiely, Cheryl J. Smith, Amy L. Zhang, Symone Jordan, Obadi M. Obadi, Anuoluwapo Ajao, Yao Tettey, Richard B. Biritwum, Andrew A. Adjei, James E. Mensah, Robert N. Hoover, Frank J. Jenkins, Rick Kittles, Ann W. Hsing, Xin W. Wang, Christopher A. Loffredo, Clayton Yates, Michael B. Cook, Stefan Ambs
Summary: There are differences in immune-oncology marker profiles between African and European descent men, particularly in suppression of tumor immunity and chemotaxis. These differences may contribute to the higher burden of prostate cancer in men of African ancestry. This has important implications for cancer therapy guidance.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
V. Vlaeminck-Guillem
Summary: Exosomes play a significant role in cancer research, including their involvement in pathophysiological mechanisms, as biomarkers, and as therapeutic tools. However, their use in routine clinical practice and management of prostate cancer still requires further confirmation and generalization.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ziruoyu Wang, Yanan Li, Wensi Zhao, Shuai Jiang, Yuqi Huang, Jun Hou, Xuelu Zhang, Zhaoyu Zhai, Chen Yang, Jiaqi Wang, Jiying Zhu, Jianbo Pan, Wei Jiang, Zengxia Li, Mingliang Ye, Minjia Tan, Haowen Jiang, Yongjun Dang
Summary: In this study, 35 Chinese PCa primary cell models were established to capture specific characteristics among PCa patients, including gene mutations, mRNA/protein/surface protein distributions, and pharmaceutical responses. AGR2 was identified as a pre-operative prognostic biomarker in PCa through multi-omics analyses. Crizotinib was found to be a selective compound for malignant PCa primary cells. The integrated multi-omics approach provided a comprehensive understanding of PCa biomarkers and pharmacological responses.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Oncology
Alice Tew, Leila Khoja, Lalit Pallan, Neil Steven
Summary: This study retrospectively reviewed patients with immune-related hepatitis following treatment with immune-checkpoint inhibitors for advanced melanoma. The results showed that most patients developed immune-related hepatitis when treated with the combination of ipilimumab and nivolumab. The study also found that some patients had resolution of hepatitis without the use of corticosteroids.
JOURNAL OF ONCOLOGY PHARMACY PRACTICE
(2023)
Article
Oncology
Wendy W. Y. Choi, Catherine Sanchez, Jiao Jiao Li, Mojdeh Dinarvand, Hans Adomat, Mazyar Ghaffari, Leila Khoja, Fatemeh Vafaee, Anthony M. Joshua, Kim N. Chi, Emma S. Tomlinson Guns, Elham Hosseini-Beheshti
Summary: EV secreted from cancer cells, which carry distinct cellular components, could be potential markers for disease initiation, progression, and treatment response. The study found significant differences in the composition of EV derived from biological fluids of castration-resistant prostate cancer patients compared to healthy controls. Specific EV proteins common in both serum and urine samples of prostate cancer patients were identified, suggesting their potential as markers for prostate cancer.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Letter
Urology & Nephrology
Richard Kelly, Andrew Jensen, Nathasha Karunaratna, Shirley Wong, Julia Shapiro, Andrew Weickhardt, Phillip Parente, Arun A. Azad, Anthony Uccellini, Javier Torres, Francis Parnis, Jeffrey Goh, Edmond M. Kwan, Stephen Brown, Christopher Steer, Mark Warren, Peter Gibbs, Ben Tran, Angelyn Anton
Review
Oncology
Richard D. Carvajal, Joseph J. Sacco, Martine J. Jager, David J. Eschelman, Roger Olofsson Bagge, J. William Harbour, Nicholas D. Chieng, Sapna P. Patel, Anthony M. Joshua, Sophie Piperno-Neumann
Summary: Uveal melanoma is a rare form of melanoma that occurs in the uveal tract of the eye, and it has distinct characteristics from cutaneous melanoma. Current treatments for primary uveal melanoma, such as radiotherapy and enucleation, can achieve local control in most patients, but distant metastases, especially in the liver, still occur in a significant number of cases. Until January 2022, no systemic therapy had been approved for metastatic uveal melanoma, leading to poor prognosis for these patients. However, recent studies have identified important genomic and immunological features of uveal melanoma, leading to the development of novel treatments, including tebentafusp, which has received regulatory approval.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Article
Urology & Nephrology
Kenneth Chen, Jonathan O'Brien, Aoife McVey, Pocharapong Jenjitranant, Brian D. Kelly, Veeru Kasivisvanathan, Nathan Lawrentschuk, Declan G. Murphy, Arun A. Azad
Summary: Androgen deprivation therapy (ADT) has been the standard treatment for newly diagnosed metastatic prostate cancer, but the adoption of combination therapy is low despite evidence-based recommendations.
NATURE REVIEWS UROLOGY
(2023)
Correction
Oncology
A. Rodrigues, R. Cosman, A. M. Joshua
BRITISH JOURNAL OF CANCER
(2023)
Editorial Material
Oncology
A. Rodrigues, R. Cosman, A. M. Joshua
Summary: Metastatic uveal melanoma has a poor prognosis and different pathophysiology from cutaneous melanoma, limiting treatment options. Targeted therapy with darovasertib towards protein kinase C is well tolerated and shows early signs of efficacy, indicating the need for further exploration and combination strategies.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
David Pook, Daniel M. Geynisman, Joan Carles, Filippo de Braud, Anthony M. Joshua, Jose Luis Perez-Gracia, Casilda Llacer Perez, Sang Joon Shin, Bruno Fang, Minal Barve, Marco Maruzzo, Sergio Bracarda, Miso Kim, Yannick Kerloeguen, Jorge Daniel Gallo, Sophia L. Maund, Adam Harris, Kuan-Chieh Huang, Victor Poon, Dhruvitkumar S. Sutaria, Howard Gurney
Summary: The combination of ipatasertib and rucaparib showed manageable safety in patients with metastatic castration-resistant prostate cancer, but did not demonstrate synergistic or additive antitumor activity in previously treated patients.
CLINICAL CANCER RESEARCH
(2023)
Letter
Urology & Nephrology
Luke C. Ardolino, Rachel Dear, Andrew J. Armstrong, Silke Gillessen, Anthony M. Joshua
Article
Oncology
Tahlia Scheinberg, Hui-Ming Lin, Michael Fitzpatrick, Arun A. A. Azad, Paul Bonnitcha, Amy Davies, Gillian Heller, Kevin Huynh, Blossom Mak, Kate Mahon, David Sullivan, Peter J. J. Meikle, Lisa G. G. Horvath
Summary: We have developed a lipid biomarker assay called PCPro, which can identify men with mCRPC who have a poor prognosis. This assay contains specific lipids and cholesterol and has been validated in independent cohorts. Prospective clinical trials are needed to determine if targeting lipid metabolism in PCPro-positive patients can improve outcomes.
PROSTATE CANCER AND PROSTATIC DISEASES
(2023)
Article
Medicine, Research & Experimental
Muhammad Ali, Simon Wood, David Pryor, Daniel Moon, Mathias Bressel, Arun A. Azad, Catherine Mitchell, Declan Murphy, Homi Zargar, Nick Hardcastle, Jamie Kearsley, Renu Eapen, Lih Ming Wong, Katharine Cuff, Nathan Lawrentschuk, Paul J. Neeson, Shankar Siva
Summary: This study aims to investigate the effectiveness of neoadjuvant stereotactic ablative body radiotherapy (SABR) with or without Pembrolizumab immunotherapy in patients with renal cell carcinoma. Twenty-six patients will be enrolled in this clinical trial and randomized to receive either SABR or SABR/Pembrolizumab. The results of this study will provide valuable insights for future clinical treatment of high-risk patients.
CONTEMPORARY CLINICAL TRIALS COMMUNICATIONS
(2023)
Editorial Material
Urology & Nephrology
Kenneth Chen, Sean Ong, Kandarpa Vasundhara, Chow Kit Mun, Isabella Williams, Ravindran Kanesvaran, John Yuen Shyi Peng, Arun A. Azad, Nathan Lawrentschuk
Article
Oncology
Neeraj Agarwal, Fred Saad, Arun A. Azad, Joaquin Mateo, Nobuaki Matsubara, Neal D. Shore, Jayeta Chakrabarti, Hsiang-Chun Chen, Silvana Lanzalone, Alexander Niyazov, Karim Fizazi
Summary: This study describes the design and rationale of the TALAPRO-3 multinational phase III trial, comparing talazoparib plus enzalutamide versus placebo plus enzalutamide in patients with metastatic castration-sensitive prostate cancer and homologous recombination repair gene alterations. The primary endpoint is investigator-assessed radiographic progression-free survival.
Article
Multidisciplinary Sciences
L. H. Porter, J. J. Zhu, N. L. Lister, S. G. Harrison, S. Keerthikumar, D. L. Goode, R. Quezada Urban, D. J. Byrne, A. Azad, I. Vela, M. S. Hofman, P. J. Neeson, P. K. Darcy, J. A. Trapani, R. A. Taylor, G. P. Risbridger
Summary: This study assessed the efficacy of Lewis Y antigen (LeY)-specific CAR T cells in patient-derived xenograft (PDX) models of prostate cancer. The researchers found that prior treatment with carboplatin improved the effectiveness of CAR T cell therapy, possibly through inducing an inflammatory response and enhancing T cell infiltration in the tumor microenvironment.
NATURE COMMUNICATIONS
(2023)
Article
Urology & Nephrology
Kenneth Chen, Louise Kostos, Arun A. Azad
Summary: The landscape of advanced prostate cancer treatment has undergone significant changes, with a shift towards combination therapies and upfront treatment intensification based on robust clinical data. Tailoring treatment according to metastatic disease burden is important, but defining disease volume has become more controversial due to next generation molecular imaging. Future studies should focus on identifying biomarkers to guide treatment intensification or de-escalation in specific patient populations.
WORLD JOURNAL OF UROLOGY
(2023)