Mustafa Raoof, MD, MS, a surgical oncologist and researcher specializing in gastrointestinal cancers at City of Hope, was recently awarded a Pancreatic Cancer Action Network Career Development Award (PanCAN) and a Young Investigator Award from the National Comprehensive Cancer Network® (NCCN).
“I’m very humbled and honored that our research focus is of interest,” Dr. Raoof said. The grants will allow him to study two new approaches to treating pancreatic cancer.
Mustafa Raoof, MD, MS
Unique Vulnerability in Replication
Pancreatic cancer cells are masters of survival, replicating and proliferating even after treatment has severely damaged them. In fact, they often become stronger as a result. However, within this process lie the seeds of their own destruction, which is what the PanCAN study will explore.
“The transcription machinery is 100 times slower than the replication machinery,” Dr. Raoof noted. “When they collide, it’s like a speeding car hitting a pedestrian, and it can cause serious damage. We’ve had chemotherapies that inhibit replication for a long period of time, only to have the cancer return. So only targeting the replication process is not enough.”
Dr. Raoof’s study will probe the mechanisms pancreatic cancer uses to resolve the collisions, to learn how to block them. His specific aim is to discover which types of cancer cells are most dependent on the collision-avoidance mechanisms, as well as which proteins in those mechanisms would respond to drugs.
Linda Malkas, PhD
The NCCN study builds on proof-of-concept research Dr. Raoof recently completed with Linda Malkas, PhD, Dean of Translational Research and the M.T. & B.A. Ahmadinia Professor in Molecular Oncology at City of Hope. The results of that study, published in Molecular Therapy Oncolytics,1 showed that targeting a replication and repair protein known as proliferating cell nuclear antigen (PCNA) can kill pancreatic cancer cells in lab models.
1. Smith SJ, Li CM, Lingeman RG, et al: Molecular targeting of cancer-associated PCNA interactions in pancreatic ductal adenocarcinoma using a cell-penetrating peptide. Mol Ther Oncolytics 17:250-256, 2020.