Molecular Profiling in Precision Medicine in Prostate Cancer

Molecular profiling in precision medicine in oncology, specifically prostate cancer, can provide physicians a clearer picture of an individual’s cancer, enabling them to determine the origin of the cancer, the potential for disease spread, its responsiveness to treatment, and the probability of disease recurrence.

Prostate cancer is a leading cause of cancer-related death in men. Up to 40% of prostate cancers are aggressive in nature, and potentially life-threatening. Prostate cancer is driven, in large part, by androgen receptor signaling, which although effective, can also lead to castration-resistant disease.

There exists several molecular markers associated with prostate cancer development and progression, but only a few are utilized in diagnosis. The standard diagnostic modalities, such as PSA testing, are effective, but now molecular profiling is emerging as a reliable method for both predictive modeling and risk stratification.

Studies Show the Efficacy of Molecular Profiling

Data suggest gene expression based on molecular classifiers may outperform traditional clinicopathologic criteria for selecting men for cancer screening, or men with adverse therapy responses or men with adverse pathology following surgery.

A previous study found molecular pathways drive both lung and metastatic castration-resistant prostate cancer lineage switching. The study utilized data generated from the patient metastases and LuCaP PDX models to build a 26-gene transcriptomic signature for defining treatment-refractory mCRPC phenotypes. The researchers wrote that the, “data add further clinical support for the proposed mCRPC disease continuum and demonstrates that treatment-induced selective pressures can change the phenotypic and molecular landscapes of mCRPC.”

As molecular stratification in prostate cancer matures, and as cost barriers associated with clinical genomics are attenuated, emerging biomarkers may increasingly rely on more comprehensive molecular analysis. Previously, the Cancer Genome Atlas (TCGA) Research Network published a report on molecular taxonomy of primary prostate cancer in 2015. This analysis assessed genomic alterations, gene expression, and epigenetic changes in 333 primary prostate carcinomas.

The study found that three quarters of primary prostate cancers fell into 1 of 7 subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Researchers noted that thee subtypes demonstrated substantial heterogeneity with respect to epigenetic profiles as well as AR activity, which clearly clustered in a subtype dependent manner.

Overall, molecular profiling in the management of prostate cancer is becoming more and more mainstream. As research continues to advance and more and more knowledge is gained about molecular diagnostics as a viable modality, its use could become key in more effectively treating prostate cancer.