Combination of Niraparib and Lapatinib for Ovarian Cancer Treatment

Ovarian cancer is characterized by high malignancy, frequent recurrence with drug resistance, and poor 5-year survival rates. Although poly(ADP-ribose) polymerase (PARP) inhibitors like niraparib show efficacy in homologous recombination repair-deficient ovarian cancer, resistance often develops. This study aimed to evaluate the synergistic therapeutic potential of combining the epidermal growth factor receptor (EGFR) inhibitor lapatinib and the PARP inhibitor niraparib to evaluate combinatorial effects and enhance antitumor effects in ovarian cancer.

Lapatinib (EGFR inhibitor) and niraparib (PARP inhibitor) were screened from the U.S. Food and Drug Administration/China Food and Drug Administration-approved drug library. In vitro assays assessed ovarian cancer cell proliferation, clonogenicity, metastatic ability, and apoptosis. Mechanistic studies analyzed phosphorylation levels of EGFR, AKT, and ERK via biochemical assays. In vivo experiments were conducted to validate the antitumor efficacy of the drug combination.

The lapatinib-niraparib combination synergistically suppressed ovarian cancer cell proliferation, inhibited clonogenic formation and metastasis, and induced apoptosis. Mechanistically, the dual therapy reduced phosphorylation of EGFR, AKT, and ERK, indicating suppression of downstream signaling pathways. Both in vitro and in vivo experiments demonstrated significant inhibition of ovarian cancer growth with the combination treatment.

EGFR/human epidermal growth factor receptor 2-expressing ovarian cancer cells responded to lapatinib and that a synergistic effect was observed when combined with niraparib. These findings highlight its promising clinical potential for improving outcomes in ovarian cancer patients.