What is the definition of prostate cancer?
Prostate cancer represents a clinically heterogeneous disease with current treatments based on anatomical and pathological parameters. The progress in sequencing strategies has revealed genomic alterations in prostate cancer that represent clinically targetable defects and potential biomarkers. Genomic alterations in the PI3K-AKT pathway, particularly PTEN are found to be common in prostate cancer, with compounds targeting various kinases in this pathway showing promise in clinical trials. Germline and somatic defects in DNA repair genes are another avenues of potentially clinical defects, being shown to sensitize patients to PARP inhibition and drugs such as olaparib which has shown potential in phase ll clinical trials. Finally, mutations in genes involved in chromatin structure regulation are an emerging area of interest. Deletions are reasonably common in prostate cancer and may potentially associate with increased AR activity and genomic instability. These tumors have shown to be sensitive to DNA-damaging therapies with their potential in combination therapies warranting further study. This report accesses how molecular defects are influencing the landscape of prostate cancer, through the identification of biomarkers and vulnerabilities that can be clinically targeted.
According to the most recent annual projections published by Siegal et al. it is estimated that roughly 164,690 men in the US will be diagnosed with prostate cancer and 29,430 men will die in 2018. Prostate cancer remains the most common form of cancer diagnosis in men at 19% of all new cases and the second most common cause of cancer-related death in men at 9%.
While most localized prostate cancers can be controlled through either surgical or radiation options, metastatic disease is lethal with no curative options currently available. Prostate cancer is also a highly heterogeneous disease displaying highly lethal or indolent and slow properties, shown by its 10-year survival rate estimated to be around 17%. The increasing availability of efficient and affordable techniques for profiling tumors represents new grounds for characterizing the molecular factors dictating indolent/lethal disease and allowing for therapy to be tailored effectively.