A case study of clinical response to rucaparib in a patient with metastatic castration-resistant prostate cancer and a RAD51B alteration Journal Article
| Authors: | Sautois, B.; Loehr, A.; Watkins, S. P.; Schroeder, H.; Abida, W. |
| Article Title: | A case study of clinical response to rucaparib in a patient with metastatic castration-resistant prostate cancer and a RAD51B alteration |
| Abstract: | PARP inhibitors, such as rucaparib, have been well characterized in metastatic castration-resistant prostate cancer (mCRPC) associated with BRCA alterations, and the clinical activity of these agents has also been evaluated in patients with mCRPC associated with alterations in other non-BRCA DNA damage repair (DDR) genes, including RAD51B. There is likely a differential sensitivity to PARP inhibition based on the specific DDR gene altered, but research in this area is limited because of the low frequency of alterations in these genes. Here, we describe a mCRPC patient with a truncating rearrangement of RAD51B who had a radiographic and PSA response when treated with the PARP inhibitor rucaparib within the TRITON2 trial. We investigated the patients’ response parameters, circulating tumor DNA (ctDNA) fraction and tumor genomics longitudinally, using next-generation sequencing (NGS) of tissue and plasma. ctDNA fraction correlates with radiographic and PSA response and is lower during times of response. NGS did not reveal any potential genomic mechanism of acquired drug resistance. This case shows evidence for rucaparib activity in a rare patient with mCRPC and a RAD51B truncation. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. |
| Keywords: | adult; clinical article; treatment response; middle aged; dna binding protein; genetics; mutation; dna-binding proteins; case report; bone metastasis; cancer patient; cancer staging; prostate specific antigen; dna damage; dna repair; prostate cancer; gleason score; prostate-specific antigen; gene rearrangement; prostatectomy; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; indoles; androgen deprivation therapy; indole derivative; rad51 protein; castration resistant prostate cancer; tyloxapol; response evaluation criteria in solid tumors; high throughput sequencing; rucaparib; humans; human; male; article; circulating tumor dna; prostatic neoplasms, castration-resistant; parp inhibitors; metastatic castration resistant prostate cancer; rad51b; oncogenomics; poly(adp-ribose) polymerase inhibitors; ex-smoker; rad51b protein, human |
| Journal Title: | Current Oncology |
| Volume: | 29 |
| Issue: | 6 |
| ISSN: | 1198-0052 |
| Publisher: | Multimed Inc |
| Date Published: | 2022-06-01 |
| Start Page: | 4178 |
| End Page: | 4184 |
| Language: | English |
| DOI: | 10.3390/curroncol29060333 |
| PUBMED: | 35735442 |
| PROVIDER: | scopus |
| PMCID: | PMC9221801 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2022 -- Source: Scopus |
