Srinivas Sridhar, Ph.D.
Funded by LUNG FORCE
Injectable Lung Cancer Therapy with PARP Inhibitors Could Better Target Tumor Cells
Lung cancer is relatively insensitive to chemotherapy with platinum drugs and radiation therapy. An enzyme called Poly ADP ribose polymerase (PARP) repairs damaged DNA. Treating tumors with PARP inhibitors like olaparib results in selective tumor cell death. Current oral delivery of olaparib is highly inefficient due to low bioavailability, meaning only a small proportion of the drug enters the circulation and accumulates in the tumor. Using nanotechnology, we will develop and test two injectable nanoparticle formulations of olaparib. These novel targeted nanoparticle formulations will ensure the delivery of clinically relevant doses of olaparib and cisplatin specifically to the lung tumor, increasing the ability to kill cancer cells while minimizing toxic effects for both localized and metastatic tumors.
Update: We developed and tested two nanoparticle formulations of PARP inhibitors, NanoOlaparib and NanoTalazoparib, in several lung cancer cell lines. We have shown that the nanoparticles are effective as stand-alone therapy and displayed enhanced results in combination with radiation therapy. NanoTalazoparib made tumor cells more sensitive to radiation therapy, compared with free Talazoparib. These formulations will be tested in animal models to show their efficacy with and without radiation.