Researchers at Cold Spring Harbor Laboratory have identified key proteins and protein complexes that help certain carcinomas shift their cellular identity and potentially evade treatment. Two new studies, focusing on pancreatic cancer and tuft cell lung cancer, highlight molecular structures that could become targets for more precise and selective therapies.
Carcinomas, cancers that arise from epithelial tissues, can be especially difficult to treat in part because some of them can alter their cellular identity. This plasticity allows tumors to resemble entirely different cell types, such as skin cells, and may reduce the effectiveness of therapies designed for their original form, according to new work from Cold Spring Harbor Laboratory (CSHL).(sciencedaily.com)
"The tumors are notoriously plastic in their cellular identity," said Christopher Vakoc, a professor at CSHL. In recent research published in Nature Communications, his team identified a protein that determines whether pancreatic cancer cells keep their classical appearance or begin to look and act more like skin cells. In a companion study in Cell Reports, the group resolved the crystal structure of a protein complex that plays a central role in tuft cell lung cancer, a subtype of small-cell lung cancer first described by the Vakoc lab in 2018.(eurekalert.org)
These discoveries build on earlier investigations by the Vakoc lab into epigenetic mechanisms that drive tumor growth and cellular reprogramming. When the team first reported tuft cell lung cancer in 2018, they were searching for epigenetic factors that control transcription and gene regulation in cancer. Now, working with CSHL director of research Leemor Joshua-Tor, the researchers have mapped how a master regulator protein in tuft cell lung cancer binds DNA and its co‑factor, offering a potential blueprint for future epigenetic therapies aimed at slowing or stopping tumor growth.(eurekalert.org)
Vakoc says the new studies reveal vulnerabilities in hard‑to‑treat carcinomas that could "tee up targets for therapy." The overarching goal, he explains, is to find the master regulators of cellular identity in tumors so that future drugs can be designed to interfere with these factors while sparing healthy tissues. This strategy echoes the logic behind existing hormone‑based treatments for certain breast and prostate cancers, which act on specific molecular pathways rather than broadly toxic mechanisms.(eurekalert.org)
Cold Spring Harbor Laboratory reports that the research was supported by funders including the National Cancer Institute and the Howard Hughes Medical Institute. By clarifying how carcinomas reprogram themselves, the work advances understanding of tumor plasticity and may help inform more effective, targeted standards of care in the future.(sciencedaily.com)
