UNIVERSITY OF TEXAS MEDICAL CENTER: Exploiting an NQO1 "Kiss of death" for Pancreatic Cancer Therapy

Year of Grant: 2014

Location: United States

 

Historically, pancreatic ductal adenocarcinoma cancer (PDAC) has been understudied and underfunded. Yet, it is the fourth leading cause of cancer death in the United States with the lowest five-year survival rate of less than 6 percent, and is projected to become the second leading cause of cancer-related death by 2020. Currently, there are no satisfactory therapies and patients' quality of life is dismal.

 

Our grant supports the team of researchers to continue their earlier research, where they had identified a protein called NQO1, which is dramatically overexpressed in nearly all (more than 90%) pancreatic cancer cells compared to normal, healthy cells and tissue. Their novel treatment strategy involves exploiting the NQ01 expression to metabolize the novel, investigational drug ARQ761, which leads to accumulation of hydrogen peroxide specifically in cancer cells.

 

Excess hydrogen peroxide hyperactivates the DNA repair enzyme, PARP1, causing cancer cell death. Preliminary evidence has shown that the drug ARQ761 is particularly effective if administered in combination with the current standard of care therapy, Abraxane (nab-paclitaxel) and gemcitabine

 

The investigators will carry out an open label, single arm P1b study of ARQ761 (beta-lap) in combination with GEM-Nab-Pac for patients with unresectable pancreatic cancer  to determine the safety, ideal timing and dosing of combining ARQ761 with current standard of care (Gemcitabine + Abraxane).

 

The team will additionally incorporate numerous biomarker analyses to uncover clues to predict which patients would respond best to this treatment regimen, as well as to help determine whether a patient currently under treatment is responding well.

 

Upon successful completion, this study could potentially pave the way to treat pancreatic cancer more effectively by informing patients and their doctors about the efficacy of each dose of agents provided to them.