Bengaluru: Researchers at the National Centre for Biological Sciences (NCBS) have developed a method that could help identify cancer cells likely to survive treatment, potentially offering an early clue to drug resistance.
Cancer treatment kills most tumour cells, but a small fraction can survive and later contribute to the disease returning or becoming harder to treat.
These surviving cells do not always develop new genetic mutations. Instead, some can enter a state in which certain genes are switched on or off, allowing them to tolerate drugs. This state can persist as the cells divide, creating a form of cellular memory.
Identifying such ‘memory genes’ has traditionally required researchers to track how individual cells and their descendants change over time. Such experiments are difficult to carry out, particularly using patient tumour samples, where researchers usually have only a snapshot of the cells.
The NCBS team has now developed “Power-Seek”, an algorithm that can identify these genes from single-cell RNA sequencing data, which captures which genes are active in individual cells at a particular point in time.
The method was developed by Suvranil Ghosh, Shaon Chakrabarti and Archishman Raju. The researchers first tested Power-Seek using previously published data from melanoma. In that study, memory genes had been identified through detailed lineage-tracking experiments. Power-Seek was able to identify many of the same genes using only a single snapshot.
The team then applied the method to a clinical breast cancer sample and again identified memory genes that had previously been found using more labour-intensive approaches. The researchers also found that memory genes in melanoma and breast cancer shared several functions, suggesting that similar mechanisms may help cancer cells tolerate treatment across different tumour types.
“For the first time, this makes it possible to identify memory genes directly from clinical samples and, perhaps eventually, to find signatures that could be used to target these surviving cells,” Raju, assistant professor at NCBS, said.
The researchers said the findings could eventually help identify cells that are predisposed to withstand treatment even before drugs are administered. “Since memory genes are switched on even before drugs are added, our method can potentially detect future causes of drug tolerance and provide early intervention strategies,” Chakrabarti, assistant professor at NCBS, said.
The study, published in Cell Systems, is an early step towards understanding how cells that appear genetically similar can respond differently to cancer treatment. The team plans to refine Power-Seek and investigate how different memory genes interact to produce drug-tolerant cancer cells.
