Chi Lin, MD, PhD, MS
Project 1
The overall objective of this project is to identify and characterize pathway(s) contributing to radioresistance in pancreatic cancer (PC) that can be explored as novel targets for radiosensitization. Specifically, the primary goal is to validate the role of cholesterol biosynthesis (CBS) in PC radioresistance and evaluate the efficacy of Zoledronic acid (Zometa) as a novel radiosensitizer (RST) for PC in preclinical studies and Phase I/II clinical trial. The central hypotheses of this proposal are that “the cholesterol biosynthesis pathway contributes to radioresistance in PC. Also, Zometa inhibits specific pathways consistently implicated in PC radioresistance and its use will radio-sensitize PC both in vitro and in vivo”.
Global RNA-Seq analysis of peripheral blood mononuclear cells isolated from patients undergoing ZOL+RT treatment showed elevated levels of NK cells, dendritic cells, CD4+T cells, and plasma cells compared to patients treated with RT alone. In preclinical models, ZOL also exerted immunomodulatory effects on the innate and adaptive immune systems. The immunomodulatory effects of ZOL will be further studied in these patient population.
This project is collaborated with Drs. Surinder Batra, Maneesh Jain and Sarathy Seshacharyulu.
The following is the ongoing trial associated with this project:
- Hypofractionated Stereotactic Body Radiation Therapy and Fluorouracil or Capecitabine With or Without Zoledronic Acid in Treating Patients With Locally Advanced Pancreatic Cancer (N CT03073785)
Secondary investigators:
- Jean L. Grem, MD
- Kelsey A. Klute, MD
- Laura Tenner, MD
- Mridula Krishnan, MBBS
- Quan P. Ly, MD
- James C. Padussis, MD
- Bradley Reames, MD
Project 2
The overall objective of this project is to examine if BMX-001 is a good normal tissue radio-protector. The majority of rectal and anal cancer patients are treated with some form of radiation therapy. Most patients will suffer from acute and/or chronic adverse effects associated with radiation exposure, which leads to a reduced quality of life. Currently there are no FDA approved treatments to protect normal pelvic tissues from radiation damage. Our data clearly show that the manganese porphyrin, BMX-001, protects normal tissues from radiation-induced damage. In addition, BMX-001 does not interfere with the cancer killing of chemo-radiation therapy in colorectal cancer cells. Our hypothesis is that the manganese porphyrin, BMX-001, will protect normal tissues from radiation-induced damage while not protecting the cancer cells in patients undergoing radiation therapy for anal or rectal cancers.
This project is collaborated with Dr. Rebecca E. Deegan.
The following are two ongoing trials associated with this project:
- Safety Study of BMX-001 (Radio-protector) in Patients With Newly Diagnosed Anal Cancer (NCT03386500)
Secondary investigators:
- Rebecca E. Deegan, PhD
- Laura Tenner, MD
- Kelsey Klute, MD
- Jean Grem, MD
- Mridula Krishnan, MBBS
- Trial of the Efficacy and Safety of Short and Long Course Radiation Therapy With/Without BMX-001 (NCT05254327)
Secondary investigators:
- Rebecca E. Deegan, PhD
- Laura Tenner, MD
- Kelsey Klute, MD
- Jean Grem, MD
- Mridula Krishnan, MBBS
- Quan Ly, MD
- Sean Langenfeld, MD
- Jennifer Leinicke, MD