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Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
Molecular landscape of prostate cancer: implications for current clinical trials
Galina Khemlina1, Sadakatsu Ikeda2, Razelle Kurzrock2
1Department of Geriatrics, University of California, San Diego, United States.
Abstract:
Castration-resistant prostate cancer (CRPC) is a lethal disease, and improvement with androgen-deprivation therapy has plateaued. Next-generation sequencing studies have led to significant advances in our understanding of genomic alterations in prostate cancer. The most common genomic aberrations in this malignancy are the transcription factor fusion of TMPRSS2-ETS, and mutations in TP53, AR, RB1 and PTEN/PIK3CA. Some of these alterations are actionable by drugs available in the clinic. In addition, it was recently shown that aberrations in DNA repair genes, such as BRCA2 and ATM, are present in both somatic and germline form in a significant minority of prostate cancer; these abnormalities can be targeted by drugs such as platinums and PARP inhibitors. In the era of tumour profiling, targeting molecular alterations may provide an opportunity for new therapeutic approaches. Although there are promising new agents to attack a variety of genomic signal abnormalities, biomarker-matched therapy (other than for androgens) have been utilised in only 2.0% of clinical trials (September 2011 through September 2014; https://clinicaltrials.gov) for prostate cancer. Enhanced efforts to define subsets of patients with prostate cancer based on their molecular anomalies, and match them with cognate therapies, warrant investigation.
Insights
Castration-resistant prostate cancer (CRPC) treatment needs improvement. Genomic profiling reveals actionable targets, including DNA repair gene aberrations, offering new therapeutic avenues beyond androgen deprivation.
Area of Science:
- Genomic Medicine
- Oncology
- Prostate Cancer Research
Background:
- Castration-resistant prostate cancer (CRPC) is a lethal malignancy with limited treatment advancements beyond androgen-deprivation therapy.
- Next-generation sequencing has elucidated common genomic alterations in prostate cancer, including TMPRSS2-ETS fusions and mutations in TP53, AR, RB1, and PTEN/PIK3CA.
- Aberrations in DNA repair genes (e.g., BRCA2, ATM) are found in a significant subset of prostate cancers and are targetable with specific therapies.
Purpose of the Study:
- To highlight the potential of targeting molecular alterations in prostate cancer for novel therapeutic strategies.
- To emphasize the need for increased utilization of biomarker-matched therapies in clinical trials for prostate cancer.
- To advocate for enhanced efforts in defining molecular subtypes of prostate cancer to guide personalized treatment approaches.
Main Methods:
- Review of next-generation sequencing data to identify common genomic aberrations in prostate cancer.
- Analysis of existing literature and clinical trial data (September 2011-September 2014) on biomarker-matched therapies.
- Identification of actionable molecular targets and corresponding therapeutic agents.
Main Results:
- Common genomic alterations like TMPRSS2-ETS fusions and mutations in TP53, AR, RB1, and PTEN/PIK3CA are prevalent in prostate cancer.
- DNA repair gene aberrations (BRCA2, ATM) represent a targetable subset for treatments like platinums and PARP inhibitors.
- Biomarker-matched therapy, excluding androgen-targeted treatments, was underutilized in only 2.0% of prostate cancer clinical trials.
Conclusions:
- Targeting specific molecular alterations in prostate cancer offers a promising avenue for developing new therapeutic approaches.
- There is a critical need to increase the implementation of biomarker-matched therapies in clinical trials for prostate cancer.
- Defining molecular subsets and matching them with cognate therapies is essential for advancing prostate cancer treatment.
