Genetic testing in prostate cancer management: Considerations informing primary care

Abstract

Inherited genetic mutations can significantly increase the risk for prostate cancer (PC), may be associated with aggressive disease and poorer outcomes, and can have hereditary cancer implications for men and their families. Germline genetic testing (hereditary cancer genetic testing) is now strongly recommended for patients with advanced/metastatic PC, particularly given the impact on targeted therapy selection or clinical trial options, with expanded National Comprehensive Cancer Network guidelines and endorsement from multiple professional societies. Furthermore, National Comprehensive Cancer Network guidelines recommend genetic testing for men with PC across the stage and risk spectrum and for unaffected men at high risk for PC based on family history to identify hereditary cancer risk. Primary care is a critical field in which providers evaluate men at an elevated risk for PC, men living with PC, and PC survivors for whom germline testing may be indicated. Therefore, there is a critical need to engage and educate primary care providers regarding the role of genetic testing and the impact of results on PC screening, treatment, and cascade testing for family members of affected men. This review highlights key aspects of genetic testing in PC, the role of clinicians, with a focus on primary care, the importance of obtaining a comprehensive family history, current germline testing guidelines, and the impact on precision PC care. With emerging evidence and guidelines, clinical pathways are needed to facilitate integrated genetic education, testing, and counseling services in appropriately selected patients. There is also a need for providers to understand the field of genetic counseling and how best to collaborate to enhance multidisciplinary patient care.

Oleocanthal Attenuates Metastatic Castration-Resistant Prostate Cancer Progression and Recurrence by Targeting SMYD2

“…Despite the progress made towards androgen suppression, including LH/FSH modulators, anti-androgen receptor (AR) small molecules, CYP17A and CYP27A1 inhibitors, chemotherapies, and immunotherapy, these treatments lack absolute curative efficacy, especially in mCRPC patients, and have poor overall survival and high recurrence incidence [ 1 , 2 , 3 , 4 ]. Androgen deprivation therapy (ADT) is the standard of care for initial management of advanced or metastatic PC cases, but progression to CRPC occurs within 2–3 years of initiation of ADT.…”

“…Olive oil is a key fat source in the Mediterranean diet [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 32 , 34 ]. This study team previously reported the ability of OC to inhibit mCRPC PC-3 cell viability, migration, and invasion by competitive inhibition of c-MET receptor tyrosine kinase [ 3 , 26 , 32 , 34 , 48 , 57 ]. In this study, results acquired through collaboration with Eli Lilly OIDD indicated that OC inhibited the monomethylation of p53 Lys 370 using scintillation proximity assay [ 47 ].…”

“…About 268,490 new PC cases, which may lead to 34,500 deaths, occur each year [ 2 ]. About six PC cases are diagnosed in every 10 men 65 years old or older, while the disease is rare in men under the age of 40 [ 3 ].…”

“…The most common PC metastatic sites are bone (84%), distant lymph nodes (10.6%), liver (10.2%), and thorax (9.1%) [ 3 , 4 ]. Overall, 18.4% of patients have multiple metastatic sites involved [ 4 ].…”

Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches

“…Precision medicine classifies diseases using genome sequencing to identify patients who have tumors exhibiting actionable targets and promoting more informed and accurate treatment decisions [ 81 ]. Mutations in prostate cancer-related genes BRCA1 and BRCA2 render men with mCRPC suitable for treatment with either rucaparib or olaparib, and other prostate cancer genes that have responded well to olaparib treatment, which include ATM , CDK12 , CHECK2 , CHECK1 , PALB2 , PP2R2A, and RAD54L [ 82 ]. The influence of BRCA mutations on therapeutic outcomes in a study of 1302 patients with 67 BRCA mutation carriers was investigated.…”