Abstract | BACKGROUND: CASE SUMMARY: A 61-year-old man who was diagnosed with metastatic prostate adenocarcinoma was initially hormone sensitivity, showing high Gleason score (5 + 5 = 10) and absolute positive rate (14/14 biopsied specimens). Following failure of several standard therapies, the patient progressed to mCRPC. Surprisingly, the patient showed good response to olaparib- abiraterone- prednisone combination treatment (an androgen-deprivation therapy, provided as the 'final choice' in China). Serum total prostate-specific antigen (TPSA) level reduced and symptoms remitted for 4 months. However, thereafter, serum TPSA levels began slowly increasing, indicating development of olaparib resistance. Subsequent comprehensive genomic profiling of ctDNA, screening 508 cancer-related genes by next-generation sequencing, identified 10 somatic variants as well as 3 copy number alterations. Two identified reverse missense mutations in partner and localizer of BRCA2 (PALB2) may have recovered the reading frame, restoring function of the primary germline PALB2 mutation and causing resistance to the PARP inhibitor olaparib. CONCLUSION: Reverse mutations in PALB2, discovered via genomic profiling of ctDNA, may represent a potential resistance mechanism against olaparib in mCRPC.
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Authors | Fang Yuan, Nan Liu, Ming-Zhen Yang, Xiao-Tian Zhang, Hong Luo, Hong Zhou |
Journal | World journal of clinical cases
(World J Clin Cases)
Vol. 10
Issue 11
Pg. 3461-3471
(Apr 16 2022)
ISSN: 2307-8960 [Print] United States |
PMID | 35611209
(Publication Type: Case Reports)
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Copyright | ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. |