everolimus + niraparib

Everolimus + niraparib is an investigational combination therapy consisting of two small molecule drugs, everolimus and niraparib, evaluated primarily for advanced ovarian and breast cancers. Everolimus is an mTOR inhibitor that blocks the PI3K/AKT/mTOR signaling pathway, which is important in cancer cell growth and survival. Niraparib is a PARP inhibitor that impairs DNA repair in tumor cells with homologous recombination deficiency, leading to cell death. The rationale for combining these agents stems from preclinical evidence suggesting synergistic antitumor activity when inhibiting both the PI3K/mTOR pathway and PARP-mediated DNA repair mechanisms. However, clinical studies have shown that this combination results in significant toxicity at lower doses—particularly severe hypertension and thrombocytopenia—making it not feasible for further development as a regimen due to safety concerns[1][2][3][4].