Combating CHK1 resistance in triple negative breast cancer: EGFR inhibition as potential combinational therapy

Abstract

Triple negative breast cancer (TNBC) is marked by a lack of expression of the Estrogen Receptor, Progesterone Receptor, and human epidermal growth factor receptor 2. Therefore, targeted therapies are being investigated based on the expression profiles of tumors. Due to the potential for acquired and intrinsic resistance, there is a need for combination therapy to overcome resistance. In the article by Lee et al., the authors identify that, while prexasertib (a CHK1 inhibitor) lacks efficacy alone, combination with an EGFR inhibitor provides synergistic anti-tumor effects. Advances in targeted therapy for TNBC will benefit the clinical landscape for this disease, with this study initiating a new avenue of investigation.

Keywords

CHK1 / TNBC / EGFR / chemoresistance

References

[1] Lee KJ,Bryant H,Schuler M.EGFR signaling promotes resistance to CHK1 inhibitor prexasertib in triple negative breast cancer.Cancer Drug Resist2020;3:980-91

[2] Hong DS,Bendell JC.Preclinical evaluation and phase Ib study of Prexasertib, a CHK1 inhibitor, and Samotolisib (LY3023414), a dual PI3K/mTOR inhibitor.Clin Cancer Res2021;27:1864-74

[3] Witkiewicz AK,Brough R.Targeting the vulnerability of RB tumor suppressor loss in triple-negative breast cancer.Cell Rep2018;22:1185-99 PMCID:PMC5967622

[4] Mani C,Lingareddy J,Gmeiner WH.Prexasertib treatment induces homologous recombination deficiency and synergizes with olaparib in triple-negative breast cancer cells.Breast Cancer Res2019;21:104 PMCID:PMC6729044