David Tweardy, M.D.
In the world of science, research doesn’t always lead you down the path you planned to follow. That was the case for David Tweardy, M.D., at Baylor College of Medicine, and his team, including Michael T. Lewis, Ph.D. and Mothaffar F. Rimawi, M.D., as they focused on how certain hormones affect the production of infection-fighting cells. It was while studying these hormones that they saw a connection to cancer and pivoted their research to work on developing treatments that targeted an intracellular messenger previously thought to be “undruggable.”
Tweardy’s research began by trying to understand the structures and actions of peptide hormones, or cytokines, specifically those that affected the production of infection-fighting cells. They had honed in on the hormone known as a granulocyte colony-stimulating factor, or G-CSF. While studying G-CSF, Tweardy and his team discovered stimulating cells with G-CSF activated an intracellular second messenger called STAT3. While STAT3 allowed immature blood cells to become neutrophils (a major infection-fighting cell), it was also found they helped contribute to the growth of cancer cells.
This was the turning point for Tweardy and his team. “STAT3 is among the most validated targets for cancer treatment identified in the past 20 years,” said Tweardy. “It plays a major role in 50% of all cancers; but successful targeting of STAT3 in patients has been a challenge. It has, to this point, been considered undruggable or unable to be targeted by a small molecule.”
Tweardy and his team began to develop a small molecule called TTI-101, which is currently being tested in a Phase I clinical trial. The idea is to help determine the maximum dose that patients with solid tumors can tolerate. “Patients are already being enrolled at the third dose level, and none have experienced adverse events. We also have one patient that has had a partial clinical response,” said Tweardy. “If we continue to be successful in developing TT1-101 into a cancer drug, it has the potential to treat many types of cancer, either alone or in combination with chemotherapy, radiotherapy or immune checkpoint therapy.”
Tweardy is grateful for the support he received from the V Foundation, which provided his group the opportunity to take risks other funding won’t support. “Without support from the V Foundation, TTI-101 would not have progressed to a Phase I clinical trial, and that patient who had a partial clinical response would not have new reason for hope,” said Tweardy.
This is why your donation counts. Funding from the V Foundation allows the best and brightest scientists across the country to go outside the box and develop new treatments that open more doors for patients. That leads to more lives saved and, eventually, Victory Over Cancer®.