Unexpected Cancer Target Discovered on Tumor Cell Surfaces
For decades, scientists believed the cancer-causing enzyme SRC functioned solely inside cells, driving tumor growth while remaining hidden from the immune system. Now, a groundbreaking discovery by researchers at the University of California San Francisco (UCSF) reveals that SRC as well appears on the surface of various tumor cells, offering a potential new target for cancer therapies.
SRC: From Oncogene to External Target
The SRC gene was first identified as an oncogene – a gene capable of causing cancer – in the 1970s by UCSF’s J. Michael Bishop, MD, and Harold Varmus, MD. Their work earned them a Nobel Prize in 1989 and launched the modern field of cancer genetics. Previous attempts to block the SRC enzyme with drugs have been largely unsuccessful because they affected both cancerous and healthy cells, which also require SRC to function.
How SRC Reaches the Cell Surface
Researchers found that as cancer cells rapidly divide, they generate a significant amount of cellular waste. While healthy cells efficiently break down and recycle this waste, tumor cells often become overwhelmed, leading to the expulsion of cellular debris. This process inadvertently pushes SRC onto the cell surface, making it visible to the immune system and potential therapeutic interventions.
“We saw that SRC was getting swept out onto the outer membrane, where it sat exposed like a red flag,” said Corleone Delaveris, PhD, a former postdoctoral researcher in Jim Wells’ lab at UCSF and now at Inversion Therapeutics 1.
Antibody Therapies Reveal Promise in Early Testing
The UCSF team tested antibodies designed to target SRC on the surface of cancer cells. These antibodies were engineered to carry radioactive payloads or to activate immune cells to destroy the cancer cells. In preclinical studies using mice, these targeted therapies successfully shrank tumors 2.
The research, published in Science on March 12, suggests this new target could be applicable to up to half of all tumors, including those of the bladder, colon, breast, and pancreas 3.
Specific to Tumor Cells
Importantly, the researchers discovered that SRC was present on the surface of bladder tumor cells obtained from patients at UCSF, but not on healthy bladder tissue or immune cells. This specificity is crucial for minimizing side effects and ensuring that therapies target cancer cells effectively 4.
Future Directions
UCSF has licensed the antibodies and related molecules to Inversion Therapeutics to further explore their therapeutic potential. “We went all the way from the discovery to developing two preclinical therapies that target SRC – and they worked. It’s truly exciting,” said Jim Wells, PhD, professor of Pharmaceutical Chemistry at UCSF 2.
This discovery opens new avenues for cancer treatment, potentially allowing for the use of existing immunotherapies on this newly identified tumor target.