Precision Targets for Intercepting the Lethal Progression of Prostate Cancer: Potential Avenues for Personalized Therapy

Max Christenson, Chung-seog Song, Ya Guang Liu, Bandana Chatterjee

Research output: Contribution to journalReview articlepeer-review

Abstract

Organ-confined prostate cancer of low-grade histopathology is managed with radiation, surgery, active surveillance, or watchful waiting and exhibits a 5-year overall survival (OS) of 95%, while metastatic prostate cancer (PCa) is incurable, holding a 5-year OS of 30%. Treatment options for advanced PCa—metastatic and non-metastatic—include hormone therapy that inactivates androgen receptor (AR) signaling, chemotherapy and genome-targeted therapy entailing synthetic lethality of tumor cells exhibiting aberrant DNA damage response, and immune checkpoint inhibition (ICI), which suppresses tumors with genomic microsatellite instability and/or deficient mismatch repair. Cancer genome sequencing uncovered novel somatic and germline mutations, while mechanistic studies are revealing their pathological consequences. A microRNA has shown biomarker potential for stratifying patients who may benefit from angiogenesis inhibition prior to ICI. A 22-gene expression signature may select high-risk localized PCa, which would not additionally benefit from post-radiation hormone therapy. We present an up-to-date review of the molecular and therapeutic aspects of PCa, highlight genomic alterations leading to AR upregulation and discuss AR-degrading molecules as promising anti-AR therapeutics. New biomarkers and druggable targets are shap-ing innovative intervention strategies against high-risk localized and metastatic PCa, including AR-independent small cell-neuroendocrine carcinoma, while presenting individualized treatment opportunities through improved design and precision targeting.

Original languageEnglish (US)
Article number892
JournalCancers
Volume14
Issue number4
DOIs
StatePublished - Feb 1 2022

Keywords

  • Androgen receptor axis
  • Cancer genome
  • Castration resistance
  • High-risk prostate cancer
  • Immunotherapy
  • Neuroendocrine carcinoma
  • PARP inhibition
  • Precision targeting

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Precision Targets for Intercepting the Lethal Progression of Prostate Cancer: Potential Avenues for Personalized Therapy'. Together they form a unique fingerprint.

Cite this