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PerturbFate Maps Shared Drivers of Melanoma Drug Resistance

The single-cell tool shifts the focus from chasing many mutations to hitting shared control points.

Overview

  • Rockefeller University researchers report in Nature a platform that links gene edits in single cells to the molecular changes those edits trigger.
  • Using melanoma cells treated with the BRAF inhibitor Vemurafenib, the team perturbed 143 resistance-linked genes and profiled more than 300,000 single cells.
  • Many different gene changes pushed cells into the same drug‑resistant state, revealing a common program that explains why diverse mutations can yield the same outcome.
  • The study highlights actionable control points, including a route from the Mediator complex to the VEGFC survival signal, and blocking VEGFC stopped growth of resistant cells in culture.
  • The group released their experimental and software tools and plans to move into animal studies and other diseases, while noting that current results come from lab-grown cells rather than patients.