ForNow, a research team at the University of Alabama at Birmingham (UAB) has identified an overlooked structural weakness in the cancer’s architecture that existing drugs entirely miss.
The research centers on a voltage-gated sodium channel called . In healthy biology, is typically confined to nerve cells, where it regulates crucial pain signaling. For medullary thyroid cancer cells, however, the channel aberrantly manifests at a significant scale.
In metastatic MTC cell lines, expression runs 400 times higher than the next closest sodium channel subtype () and 25 times higher than . Crucially, normal thyroid cells show no detectable expression whatsoever. The channel is similarly absent in other thyroid cancer variations, such as papillary and anaplastic, as well as neuroendocrine tumors of the lung or pancreas.
“Our studies using medullary thyroid cancer cell lines and patient specimens confirmed that VGSC subtype is uniquely expressed in aggressive MTC,” notes Dr. Sadanandan Velu, professor of chemistry at UAB and researcher at the O’Neal Comprehensive Cancer Center. “
It is not expressed in normal thyroid cells and tissues, which makes it an attractive therapeutic target.”
A drug engineered to hit a target that cancer cells carry but healthy cells do not is far less likely to cause the systemic toxicity that makes traditional TKIs so difficult for patients to tolerate.
Sodium channel blockers work by strictly restricting the flow of sodium ions across the cellular membrane. This targeted blockade blunts the cells’ ability to migrate and invade surrounding tissue, the two precise cellular mechanics that drive lethal metastasis.
Data from the team’s ongoing development pipeline highlights a clear trajectory toward a viable clinical drug candidate:
The current standard of care for advanced MTC relies on four FDA approved TKIs: vandetanib, cabozantinib, selpercatinib, and pralsetinib. While these therapies successfully extend progression-free survival, they do not offer a permanent cure.
Because blockers specifically inhibit cellular invasion rather than relying on blunt cytotoxic destruction, they present a entirely separate therapeutic pathway that could bypass the mutation-driven drug resistance common to TKIs.
Dr. Velu is advancing the compound pipeline alongside Dr. Renata Jaskula-Sztul, an associate professor in UAB’s Division of Breast and Endocrine Surgery, and doctoral researcher Piyasuda Pukkanasut. While the research remains in the basic science stage with clinical trials still on the horizon, the team’s objective remains fixed on the primary driver of MTC mortality. Improving the baseline survival rate for patients facing hepatic metastasis is what continues to anchor the timeline of this project.
Breakthrough discovery offers hope for thyroid cancer with no current treatments – Futura, le média qui explore le monde
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