By Elodie Vaz | Published on March 19, 2026 | 3 min readFor over
half a century, the oncogenic enzyme SRC has held a central place in cancer
research. Identified in the 1970s as the first oncogene by J. Michael Bishop
and Harold Varmus—a discovery awarded the Nobel Prize in 1989—this finding
profoundly transformed the genetic understanding of cancer. SRC encodes an
enzyme involved in intracellular signaling pathways that promote tumor
proliferation.
Until
recently, researchers believed that this protein remained confined within
cancer cells, making it difficult to access using immunotherapeutic approaches.
A study
conducted at the University of California, San Francisco (UCSF), and published
on March 12 in Science, challenges this paradigm. The researchers show
that SRC can appear on the surface of many tumor cells, opening the way to a
new targeted therapeutic strategy.
Identifying
an antibody-accessible target
The team
led by Jim Wells aimed to determine whether certain proteins considered
intracellular could, under specific conditions, become accessible to
antibody-based drugs. “No one had thought to look for it outside,” the
researcher explained in a press release. “Our discovery allows us to test
proven immunotherapies on this new tumor target.”
The
scientists focused in particular on rapidly dividing tumor cells, known to
produce large amounts of molecular waste.
Exploring
SRC intracellular trafficking
To
understand how SRC could reach the cell surface, the researchers tracked the
protein in cancer cells grown in vitro.
In healthy
cells, waste is typically stored in vesicles and then recycled by degradation
systems. However, in fast-growing tumors, these mechanisms become saturated.
Vesicles filled with waste then fuse with the plasma membrane and expel their
contents outside the cell.
Observations
revealed that SRC can be carried along in this elimination process. “We found
that SRC was projected onto the outer membrane, where it remained exposed like
a red flag,” explained Corleone Delaveris, first author of the study.
A target
present across many tumors
Analyses of
human tumor samples confirmed the presence of SRC on the surface of bladder
cancer cells, while it was absent in healthy bladder tissue and immune cells.
This specificity suggests it could be a relevant target for directing
therapeutic antibodies toward tumor cells.
The
researchers then tested several preclinical approaches. In collaboration with
UCSF radiologist Michael Evans, the team developed radioactive antibodies
targeting SRC and evaluated them in mice bearing human tumors. The antibodies
accumulated in cancer cells and contributed to reducing tumor size.
Other
antibodies were also designed to recruit the immune system and promote tumor
cell destruction. According to the researchers, this target could be relevant
in nearly half of tumors, including breast, colon, pancreatic, and bladder
cancers.
Toward
new immunotherapy strategies
These
results suggest that the accumulation of molecular waste in tumors can expose
proteins on their surface that are normally invisible to treatments. Exploiting
these “waste products” could therefore provide a new reservoir of therapeutic
targets.
UCSF has
already licensed these antibodies to the company Inversion Therapeutics to
explore their clinical development. “We went from discovery to developing two
preclinical therapies targeting SRC, and they worked,” said Jim Wells. “It’s
really exciting.”
In the
longer term, this approach could encourage researchers to revisit other
proteins considered strictly intracellular. If these “molecular waste”
components are frequently exposed on the surface of cancer cells, they could
constitute a new generation of targets for anticancer immunotherapies.
Read next: Colorectal cancer on the rise
About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.
