Researchers from Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard found 56 genes that didn't cause normal cells to turn cancerous and instead were essential to all cells but get disrupted as cancer progresses.
"One of the hallmarks of cancer is genomic instability, in which entire sections of chromosomes can be lost or duplicated many times over," Rameen Beroukhim, one of the researchers said.
"The result is that genes residing in those areas are either deleted or significantly over-copied," Beroukhim said.
This often leads to partial loss of essential genes, leaving cancer cells with barely enough of these genes to survive. Such genes become lifelines for tumour cells.
Blocking them with drug molecules is far more likely to harm cancer cells than normal cells.
"When tumour suppressor genes are lost, it's common for several nearby genes - which play no role in cancer development - to be lost as well," study's co-author William Hahn said.
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The study scanned more than 3,100 samples of different types of cancers, and found that most were missing copies of genes across wide stretches of the genome.
They analysed data from Project Achilles, a Dana-Farber research effort that has uncovered genes critical to the reproduction of cancer cells.
Researchers combined both sets of data to find instances where the loss of one copy of a gene rendered the remaining copy especially important to the cancer cell.
From an initial pool of 5,312 genes, researchers identified 56 that met the desired criteria. They dubbed them CYCLOPS genes (for Copy number alterations Yielding Cancer Liabilities Owing to Partial loss).
When the researchers ranked the 56 CYCLOPS genes by the degree to which the cancer cells were dependent on them, the gene that topped the list was PSMC2.
When they administered a PSMC2-blocking agent to mice whose tumours lacked a copy of the PSMC2 gene, the tumours shrank dramatically.
"It was a powerful demonstration of the potential of CYCLOPS genes to serve as targets for cancer therapies," Beroukhim said.
The fact that CYCLOPS genes are often neighbours of tumour suppressor genes makes them even more attractive as drug targets, the study authors said in a statement.
In cancers with missing copies of tumour suppressor genes, blocking nearby CYCLOPS genes offers a promising way to dampen cell proliferation.
The study was published in the journal Cell.