Blocking MYC Shifts Aggressive Pancreatic Cells Back — SkimNews
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- NYU Langone Health and its Perlmutter Cancer Center analyzed gene activity in 443,451 individual pancreatic ductal adenocarcinoma cells from 62 tumors belonging to 56 patients, with the results published October 13 in Nature Genetics.
- Pancreatic ductal adenocarcinoma tumors contained roughly two to 11 distinct clones each, DNA changes let cells move between the less aggressive classical and more aggressive basal states, and differences in DNA copy numbers lined up with the cell types present in each tumor.
- MYC activity was heightened in the most aggressive basal cell populations, and blocking MYC in laboratory experiments shifted those cells back toward the less aggressive classical state while making them more exposed to immune cells.
- TIGIT activity rose in certain tumor clones at the same time PD1 activity fell, a combination the researchers said may help explain why PD1-targeted immunotherapies have shown limited effectiveness against pancreatic cancer.
- Aristotelis Tsirigos said clinical trials investigating drugs that inhibit MYC or TIGIT are already underway for pancreatic ductal carcinoma and other cancers, and said the findings underscore the need for larger studies examining distinct cancer cell states and tailoring treatments to them.
- Despoina Kalfakakou described the study as the most granular view to date of pancreatic ductal adenocarcinoma, revealing how ongoing genetic reshaping drives tumor evolution over the course of disease.
- Pancreatic ductal adenocarcinoma kills nearly 85 percent of patients within five years of diagnosis, according to the study, which also tracked tumor samples from six patients both before and after chemotherapy.
Why it matters: With nearly 85 percent of pancreatic ductal adenocarcinoma patients dying within five years of diagnosis, pinpointing MYC and TIGIT in the most aggressive and immune-evasive clones matters because inhibitors of both genes are already in clinical trials. The 443,451-cell, 62-tumor analysis gives those programs a cell-level map of which clone to target.
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