Mechanistic insights into molecular targeting and combined modality therapy for aggressive, localized prostate cancer

Alan Dal Pra, Jennifer A. Locke, Gerben Borst, Stephane Supiot, Robert G. Bristow

Research output: Contribution to journalReview articlepeer-review


Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa.

Original languageEnglish
Article number24
JournalFrontiers in Oncology
Issue numberFEB
Publication statusPublished - 16 Feb 2016


  • Biomarkers
  • Combined modality
  • Genomics
  • Molecular oncology
  • Prostate cancer
  • Radiotherapy
  • Targeted therapies

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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