Novel Nanoformulations Enhance the Versatility Small Molecule Therapeutics

PARP inhibitors exploit defects in DNA repair pathways to selectively target cancerous cells. As such, Talazoparib (TLZ), a potent PARP inhibitor, offers a way to target the biology of a number of cancers with DNA repair defects until these tumors develop resistance. In clinical trials TLZ, an orally available drug, enhanced therapeutic efficacy compared to chemotherapy but resulted in similar toxicity profiles. Systemic administration of nanoparticles bypasses the first-pass metabolism of oral drugs while preferentially accumulating in tumors due to leaky tumor vasculature. A nanoformulation of TLZ (NanoTLZ) has been optimized in order to enhance therapeutic efficacy and decrease non-specific toxicity. The versatility of this platform has been explored as both an intravenous and intraperitoneal therapy. NanoTLZ has shown promise as both a monotherapy and combination therapy for a variety of cancers.