In laboratory experiments, blocking an enzyme involved in serine metabolism reduced growth-related signals in cells that no longer responded well to dabrafenib.
Researchers created a laboratory cell line of BRAF V600E anaplastic thyroid cancer that had become resistant to dabrafenib, a drug that blocks the cancer-driving BRAF protein. Compared with the original cells, the resistant cells had higher levels of PHGDH, an enzyme involved in making serine, and EGFR, a protein that can activate growth signals.
Blocking PHGDH with NCT-503 changed gene networks linked to flexible tumor-cell behavior, stem-like traits and EGFR–MAPK signaling. The inhibitor reduced colony formation, stemness-associated markers and MAPK activity, either alone or with dabrafenib, in the laboratory cell models.
What the cell tests found
The researchers established a dabrafenib-resistant anaplastic thyroid cancer cell line called 8505C-R and compared it with the original parental cells. The resistant cells showed elevated levels of PHGDH and EGFR. Gene-expression analysis found that inhibiting PHGDH with NCT-503 reprogrammed networks associated with tumor-cell plasticity, stem-like characteristics and overactive EGFR–MAPK signaling. LRIG1, a negative regulator of EGFR, also changed after PHGDH inhibition, pointing to a possible feedback connection between serine metabolism and receptor signaling. In cell-based tests, PHGDH inhibition alone or combined with dabrafenib reduced colony formation, stemness-associated markers and MAPK pathway activity.
Evidence and limits
The study was conducted in laboratory-grown anaplastic thyroid cancer cells, comparing a dabrafenib-resistant cell line with its original parental cells. Researchers used cell-growth, colony-formation, gene-expression and molecular-signaling assays, including the selective PHGDH inhibitor NCT-503. The findings do not show whether PHGDH inhibition is safe or effective in people, and the abstract does not report animal or clinical results.
// Source
Cell Death Discovery · 2026 · DOI: 10.1038/s41420-026-03293-7
Authors: Sung Young Kim, Mi‐Hyeon You
Institutions: Konkuk University
