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News
Mayo Clinic researchers found that MAPK-inhibiting drugs can "reprogram" aggressive thyroid cancer cells to re-express a surface marker, making them visible to CAR-T cells again. In preclinical models, combining these drugs with TSHR-targeted CAR-T therapy outperformed either treatment alone. The approach could offer a new framework for tackling solid tumors where CAR-T therapy has historically struggled.
CAR-T cell therapy has revolutionized treatment for blood cancers, but solid tumors have been a tougher nut to crack — largely because cancer cells can shed the surface markers that engineered immune cells are designed to target. Now, Mayo Clinic researchers have found a clever workaround: instead of further engineering the immune cells, they reprogrammed the tumor itself.
In a preclinical study published in Molecular Cancer, the team showed that MAPK-inhibiting drugs — trametinib and dabrafenib, already approved for advanced thyroid cancer — can restore expression of the thyroid-stimulating hormone receptor (TSHR) on aggressive anaplastic thyroid cancer cells. When combined with TSHR-targeted CAR-T cells, the combo produced stronger tumor control and improved survival compared to either treatment alone. Crucially, the MAPK inhibitors didn't hamper the CAR-T cells' ability to multiply or attack — they simply reopened a window of vulnerability.
Key Takeaways:
Why it matters: This strategy — using targeted drugs to make tumors "visible" to immune therapy — could serve as a broader blueprint for improving CAR-T efficacy across multiple solid tumor types where antigen loss is a persistent challenge.
