AI Article Synopsis
- CHEK2 plays a role in homologous recombination repair (HRR) and individuals with harmful variants in this gene are at higher risk for developing breast cancer and potentially other cancers.
- PARP inhibitors (PARPi) are effective for cancers with HRR deficiencies, such as those caused by BRCA1/2 mutations, but they have shown little success in treating cancers linked to CHEK2 variants.
- Research indicates that cancers from individuals with biallelic CHEK2 variants do not exhibit traits associated with HRR deficiency, explaining the lack of efficacy of PARPi treatment for these patients.
Article Abstract
CHEK2 is considered to be involved in homologous recombination repair (HRR). Individuals who have germline pathogenic variants (gPVs) in CHEK2 are at increased risk to develop breast cancer and likely other primary cancers. PARP inhibitors (PARPi) have been shown to be effective in the treatment of cancers that present with HRR deficiency-for example, caused by inactivation of BRCA1/2. However, clinical trials have shown little to no efficacy of PARPi in patients with CHEK2 gPVs. Here, we show that both breast and non-breast cancers from individuals who have biallelic gPVs in CHEK2 (germline CHEK2 deficiency) do not present with molecular profiles that fit with HRR deficiency. This finding provides a likely explanation why PARPi therapy is not successful in the treatment of CHEK2-deficient cancers.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216722 | PMC |
| http://dx.doi.org/10.1093/jncics/pkae044 | DOI Listing |
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