A long‑standing mystery in the deadliest breast cancer just yielded 81 new treatment targets
Using an in‑vivo CRISPR‑KOALA screen of >3,700 genes altered in basal‑like triple‑negative breast cancer, researchers identified 81 novel driver genes, 90 % of which were missed by cell‑culture assays, including the driver PLGRKT that supports hypoxic tumor survival.
A CRISPR‑based, in‑vivo screen (CRISPR‑KOALA) directed at genes affected by chromosomal rearrangements in basal‑like (triple‑negative) breast cancer identified 81 previously unrecognized driver genes from a panel of >3,700 aneuploidy‑associated genes. 90 % of these drivers were undetected in standard cell‑culture assays, highlighting the advantage of an in‑vivo approach. The most potent driver, PLGRKT, promotes tumor cell survival under hypoxia by activating a metabolism‑adapted energy pathway, representing a promising therapeutic target.
The discovery uncovers a major source of genetic drivers in the most aggressive form of breast cancer, providing new avenues for precision therapies where currently there are few options. It demonstrates that in‑vivo functional genomics can reveal targets invisible to traditional models, potentially accelerating drug development for basal‑like breast cancer.
Bizonyítékszint: Klinikai vizsgálat. Formális klinikai vizsgálati eredmény.
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- The SURVIVE study (NCT05658172): Bringing breast cancer aftercare to the 21st century: Study protocol of a Phase III clinical trial comparing liquid biopsy guided vs. Standard of care surveillance for intermediate to high-risk breast cancer survivors - PMC