ipatasertib + rucaparib

Ipatasertib + rucaparib is a combination of two small molecule drugs being evaluated for the treatment of advanced cancers, particularly metastatic castration-resistant prostate cancer (mCRPC), and also in advanced breast and ovarian cancer. Ipatasertib is an AKT inhibitor that targets the serine/threonine kinase AKT, part of the PI3K/AKT signaling pathway, which is frequently dysregulated in tumors. Rucaparib is a PARP inhibitor that targets poly(ADP-ribose) polymerase enzymes (mainly PARP1, PARP2), which are involved in DNA repair. This combination is designed to leverage potential synthetic lethality in tumors with homologous recombination deficiencies or PTEN loss, but Phase Ib studies have shown that while the regimen is tolerable, it does not demonstrate clear synergistic or additive antitumor activity in mCRPC patients previously treated with androgen receptor inhibitors[1][2][3][4][5].