Dr. Richard Tuli

Cedars-Sinai Medical Center

Grant Amount: $323,423

Pancreatic adenocarcinoma is a devastating disease with the lowest survival rate of any solid cancer. Gemcitabine chemotherapy and radiotherapy given concurrently remain the mainstay treatments for patients with locally advanced pancreatic cancer, which cannot be removed by surgery, but also has not spread to other areas of the body. Both gemcitabine and radiotherapy kill tumor cells by interfering with their DNA, the genetic blueprint. Veliparib is a poly (ADP-ribose) polymerase (PARP)1/2 inhibitor; PARP1/2 proteins are also involved in DNA repair. Studies have shown that inhibiting PARP1/2 activity can significantly enhance the effects of radiotherapy and chemotherapy in killing tumor cells. Our own laboratory work has shown excellent synergy between veliparib (a PARP inhibitor), radiotherapy and gemcitabine in killing pancreatic cancer cells grown in culture, and in prolonging survival in mice with pancreatic tumors.

Based upon these promising results and with the generous support of the PHASE ONE Foundation and Diane V. Allen, Dr. Richard Tuli and his team are currently enrolling patients in a first-in-human, investigational clinical study (phase I) to test the safety and efficacy of veliparib in combination with gemcitabine and radiotherapy in patients with locally advanced pancreatic cancer. Prior to and during therapy, patient tumor and blood samples will also be tested for levels of different DNA repair proteins and mutations, such as BRCA1/2. This molecular “signature” will hopefully serve as a “biomarker” to predict how the patient and tumor are responding to treatment. We are hopeful that we will be able to select out the subset of favorable patients who respond to this regimen, and design future studies (phase 2/3) by “personalizing” treatments using PARP1/2 inhibitors.