Scientists find 81 hidden genes driving deadly breast cancer

Sinai Health researchers published findings in Nature identifying 81 new cancer-driving genes in basal-like triple-negative breast cancer, the deadliest form.eurekalert+1
The team developed a tool called CRISPR-KOALA to screen over 3,700 genes in mice, detecting drivers that standard cell culture experiments had missed.eurekalert+1
One gene, PLGRKT, emerged as a key tumor promoter by helping cancer cells survive without oxygen, making it a candidate for targeted therapy.nature+1

A team of scientists at Sinai Health in Toronto has uncovered 81 previously unknown genes involved in basal-like triple-negative breast cancer, solving a long-standing mystery of how chromosomal chaos fuels one of the disease's deadliest forms. The findings, published in Nature on July 8, open new paths toward targeted treatments for a cancer that has long resisted precision therapy.eurekalert+2

A New Tool to Crack the Code

The study was led by Dr. Daniel Schramek, Deputy Director of Discovery Research at Sinai Health's Lunenfeld-Tanenbaum Research Institute, and Dr. Khalid Al-Zahrani, now at the University of Toronto's Donnelly Centre. Their team developed a gene-editing tool called CRISPR-KOALA — Knockout and Activation Linked Assay — which for the first time can both silence and activate genes within a single mouse, mimicking the chromosomal duplications and deletions seen in patients.nature+1

Using CRISPR-KOALA, the researchers screened more than 3,700 genes on chromosomes commonly rearranged in basal-like breast cancer and identified 90 cancer-driving genes, 81 of which had never been linked to the disease. Ninety percent of these genes went undetected in standard cell culture experiments, explaining why they had eluded researchers for years.eurekalert+1

"The reason we hadn't found many of these driving genes before is that we were working in cell culture models," Dr. Schramek said. "Now that we can study this cancer directly in a living system, we can observe the biological intricacies that only emerge in the context of a real tumour environment."eurekalert

Why It Matters

Basal-like breast cancer disproportionately affects younger women of colour and lacks the three receptor types that allow clinicians to target other breast cancers with precision drugs. While five-year survival rates for many breast cancers approach 95 percent, triple-negative patients face far worse outcomes due to the absence of known genetic drivers.medicalxpress+1

Among the newly identified genes, one called PLGRKT emerged as a potent tumor promoter. It enables cancer cells to survive in oxygen-starved regions deep inside tumors by switching to an alternative metabolic pathway, actively fueling growth. The researchers say it represents a compelling candidate for future targeted therapy.eurekalert+1

What Comes Next

"Combining all of that enabled us to uncover roles for many genes that we did not know were driving breast cancer and to start thinking about how to tackle BLBC in a targeted way," Dr. Al-Zahrani said.eurekalert

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