Reference Detail

Ref Type

Journal Article

PMID

(36181052)

Authors

Lai YH, Tung KC, Chen SC

Title

Durable response to olaparib combined low-dose cisplatin in advanced hepatocellular carcinoma with FANCA mutation: A case report.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Medicine	101	39	2022 Sep 30	e30719	Medicine (Baltimore)

URL

Abstract Text

To date, there is no actionable gene has been discovered in hepatocellular carcinoma (HCC). Tumor cells with DNA damage response and repair (DDR) gene loss-of-function mutation is sensitivity to poly-ADP-ribose polymerase (PARP) inhibitors and platinum chemotherapy in ovarian, prostate and pancreatic cancers. There is a case report demonstrated the efficacy of PARP inhibitor for BRCA2 mutation that belongs to DDR gene in HCC, which suggested the potential role of PARP inhibitor for HCC with DDR gene mutation.We reported a 44-year-old woman with non-viral HCC who was refractory to multiple treatment including target therapy, immunotherapy, and chemotherapy. The tumor tissue was submitted to next-generation sequencing using the commercially available ACTOnco®+ (ACT Genomics, Taiwan) assay that interrogates 440 and 31 cancer-related genes and fusion genes, respectively.A truncating mutation FANCA p.Q1307fs was also observed. The tumor was microsatellite stable and had low tumor mutational burden of 4.5 muts/Mb.Given FANCA belongs to DDR genes, the inactivation evoked the idea of using PARP inhibitor and cisplatin. Therefore, the patient started to use olaparib combined with low-dose cisplatin (30 mg/m2, every 4 weeks) therapy in December 2019. Significant reduction in the tumor marker level in 1 month (PIVKA-II from 17,395 to 411 ng/dL) and follow-up CT scan showed stable disease. Her tumor did not progress until December 2020 with a progression-free survival of 12 months.We report the first case of FANCA-mutated HCC that responded well to olaparib and low-dose cisplatin. This addressed the potential therapeutic role of DDR gene mutation in HCC and the possible synergistic effect of PARP inhibitor and cisplatin. These findings highlight areas where further investigation and effort are needed.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
FANCA	Q1307Sfs*6	frameshift	unknown	FANCA Q1307Sfs6 indicates a shift in the reading frame starting at amino acid 1307 and terminating 6 residues downstream causing a premature truncation of the 1455 amino acid Fanca protein (UniProt.org). Q1307Sfs6 has been identified in the scientific literature (PMID: 36181052), but has not been biochemically characterized and therefore, its effect on Fanca protein function is unknown (PubMed, Nov 2023).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
FANCA Q1307Sfs*6	hepatocellular carcinoma	predicted - sensitive	Cisplatin + Olaparib	Case Reports/Case Series	Actionable	In a clinical case study, Lynparza (olaparib) and Platinol (cisplatin) combination treatment resulted in decreased tumor marker level within 1 month and disease stabilization with a progression-free survival of 12 months in a patient with hepatocellular carcinoma harboring FANCA Q1307Sfs*6 (PMID: 36181052).	36181052