"What Works for Breast Cancer Should Work for Prostate Cancer, Right?"
April 18, 2021
From the Desk of Evan Yu: "What Works for Breast Cancer Should Work for Prostate Cancer, Right?"
Evan Yu, MD
The Future of CDK4/6 Inhibitors for Prostate Cancer May Need to Draw Inspiration from Goldilocks and the Three Bears -- Cyclin dependent kinases (CDKs) and D-type cyclins (CCND) have a critical role in cell cycle progression from G1 to S phase. Several tumors have been shown to have alterations of proteins involved in the activity and regulation of this complex. Multiple small molecule inhibitors have been developed to target CDK 4/6, including ribociclib, palbociclib and abemaciclib. These agents are now regulatory approved in combination with aromatase inhibitors or fulvestrant for patients with metastatic breast cancer.
CURATED BY EXPERT EDITORS: EDUCATIONAL FORUMS WITH VIDEOS, ABSTRACTS AND CONFERENCE INFORMATION
RB, or Not RB: That is the Question!
Charles J. Ryan, MD
In this letter from the editor, Dr. Charles Ryan focuses on the molecule -RB ( or, the retinoblastoma gene) and its pivotal role in prostate cancer progression. I predict that within the not too distant future, clinicians will be wanting to know the “RB status” of the tumors of the patients they are treating. Thus, in my latest effort to educate you ( and myself) about the key molecular drivers of prostate cancer progression, metastasis and how it becomes lethal, I have chosen to focus on Rb. It is likely that aberrations in Rb account for much of the misery that afflicts those with mCRPC as it is one of the key molecular drivers in the disease. One day, hopefully soon, knowing this status will drive treatment decisions.
STATE-OF-THE-INDUSTRY VIDEOS BY LEADING UROLOGY EXPERTS
Count Me In! The Metastatic Prostate Cancer Project - Eliezer Van Allen
Eliezer Van Allen, MD
Eli Van Allen shares details on The Metastatic Prostate Cancer Project, a project part of a larger nationwide genomic research project called "Count Me In" for men with advanced or metastatic prostate cancer. The Metastatic Prostate Cancer Project takes a new approach to cancer research in which researchers partner directly with men with metastatic and/or advanced prostate cancer, who share their samples and clinical information in order to speed up important discoveries.
Integrating Genomics and Genetics into Clinical Care for Prostate Cancer, A Pathologist's Perspective - Colin Pritchard
In the era that genomics and genetics are really making an impact to clinical practice and with the recent positive results of the PROfound study, Alicia Morgans and Colin Pritchard have a discussion thinking about this data, how do we implement it, and how do we work with our pathologists to make things happen?
CDK12-Altered Prostate Cancer: Clinical Features and Therapeutic Outcomes to Standard Systemic Therapies, PARP and PD1 Inhibitors
Emmanuel S. Antonarakis, MB BCh
Although once considered a homologous recombination DNA repair gene, cyclin-dependent kinase 12 (CDK12) is now thought to have a distinct role in maintaining genomic stability. In prostate cancer, inactivating CDK12 mutations, which are found in 6-7% of cases, lead to gene fusion-induced neoantigens and possibly sensitivity to PD1 inhibitors. At the Prostate Cancer Poster Session at the European Society for Medical Oncology (ESMO) 2019 Congress, Dr. Antonarakis and colleagues presented results of their study assessing outcomes of patients with CDK12 loss-of-function mutations.
Invited Discussant: (LBA50, 845PD, 846PD and 847PD)Phase 2 Study GALAHAD, CDK12-altered Prostate Cancer, Preliminary results from the TRITON2 study, and HRRm in Tumor Tissue from men with mCRPC Screened for the PROfound Study
Elena Castro, MD, Ph.D
In this session, Dr. Elena Castro discussed four prostate cancer abstracts: Pre-specified interim analysis of GALAHAD: a phase 2 study of niraparib in patients with metastatic castration-resistant prostate cancer and biallelic DNA-repair gene defect. CKD12-altered prostate cancer: Clinical features and therapeutic outcomes to standard systemic therapies, PARP inhibitors, and PD1 inhibitors. Preliminary results from the TRITON2 study of rucaparib in patients with DNA damage-repair deficient metastatic castration-resistant prostate cancer: updated analysis and central, prospective detection of homologous recombination repair gene mutations in tumor tissue from >4000 men with metastatic castration-resistant prostate cancer screened for the PROfound study.
Transitional Surrogate Endpoint for Survival in Phase II Trials for mCRPC - Assessment of Circulating Tumor Cell Number
A liquid biopsy is the analysis of blood for circulating cell free tumor DNA (ctDNA) or circulating tumor cells (CTCs). Tumor cells can be released from a primary tumor or metastatic tumor and the typical half-life of a CTC ranges from 1-2.4 hours. It is unknown if CTCs are released due to a predetermined tumor program but migration of metastatic cells into circulation is known to be dependent on chemokines such as CXCR4, CCR4, CCR7, and CCR91.