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Researchers have identified a protein essential for the survival of a particular type of tumor cell, according to a study published today in eLife.
The results, originally published on bioRxiv, suggest that the targeting of a protein called Werner's syndrome (Werner Syndrome Helicase) may represent a new opportunity for the treatment of a subgroup of cancer patients with tumors with high microsatellite instability (MSI-H).
MSI is a clinically defined feature of cancer cells that harbor defects in mismatch DNA repair (MMR), the error correction system that may occur during DNA replication. A defective MMR and MSI-H are observed in approximately 4% of all human cancer cases, with a particularly high prevalence in colorectal, endometrial and gastric cancers.
The treatment of MSI-H tumors has recently been modified with the approval of pembrolizumab, nivolumab and ipilimumab immunotherapies. However, while these drugs often result in lasting positive responses in patients with cancer by MSI-H, a possible resistance to immunotherapy means that there remains a need for more effective treatments .
"The targeted treatment against cancer relies on the exploitation of biological systems on which tumor cells support, but not healthy tissue," said lead author Simon Wöhrle, a senior scientist at the Center. Regional Boehringer Ingelheim Vienna (RCV), Austria. "Before we can develop new treatments for MSI-H cancer cells, we must first understand what helps them survive and thrive."
The team used the profiling of MSI-H cancer cells and the latest functional cell line screening data to answer this question. They demonstrated that the removal of WRN function from MSI-H cells prevented them from functioning properly and caused defects in cell division. "In particular, we found that WRN-depleted MSI-H cancer cell lines showed chromosomal disruption and genome instability, highlighting the WRN as a new vulnerability of MSI-H cells," says lead co-author Mark Petronczki. director of cancer cell signaling at Boehringer. Ingelheim RCV.
As the loss of WRN is known to cause Werner syndrome, a disease of premature aging badociated with an increased risk of developing tumors over the course of life, it has already been suggested that protein plays a key role in the suppression of you die. However, contrary to this idea, current results show that WRN has a positive survival function for specific cancer cells.
"We have demonstrated the ability to combine deep functional genomic screening data with the profiling of tumor cell lines to identify new targets in oncology," concludes author co-author Mark Pearson, vice president of Boehringer Ingelheim RCV. "Our results indicate that the pharmacological inhibition of WRN function could constitute a new targeted therapeutic strategy in MSI-H cancer in order to meet the demand for more effective drugs."
Source:
https://elifesciences.org/for-the-press/b350305d/scientists-uncover-novel-strategy-to-target-common-type-of-cancer
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