Exploiting homologous recombination repair alterations in metastatic castrate-resistant prostate cancer: a case report and literature review

Posted On 2020-02-20 07:52:56

DNA damage can occur through a variety of processes and thus DNA repair is essential for cells to maintain their genomic integrity. Homologous recombination repair (HRR) is an important cellular mechanism by which double strand DNA breaks (DSB) are corrected with high fidelity. Proteins involved in this process include BRCA1, BRCA2, RAD51, and PALB2. Alterations in this mechanism can be found in a diverse set of malignancies and evidence exists that targeting these deficiencies can result in clinical benefit. Here we present a case of a patient with relapsed, metastatic castrate-resistant prostate cancer (mCRPC) that was refractory to standard of care therapies inducing androgen blockade and taxanes. He subsequently was found to have a PALB2 mutation on molecular analysis (next generation sequencing) of his tumor which was later confirmed to be germline. Treatment with carboplatin followed by a PARP-inhibitor led to rapid control of his advanced disease. This article will review the patient’s course along with the mechanisms of DNA damage repair with a focus on HRR and the rationale for therapies targeted to exploit alterations of this process.

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