Blocking MYC shifted aggressive pancreatic cancer cells in the laboratory — ScienceDaily

Scientists at NYU Langone Health and the Perlmutter Cancer Center investigated how pancreatic ductal adenocarcinoma changes its genetic characteristics and adapts to treatment. As ScienceDaily reports, in laboratory experiments, blocking the activity of the MYC gene in aggressive basal tumor cells promoted their transition to a less aggressive classical state.

The study was published on October 13 in the journal Nature Genetics. The authors analyzed gene activity in 443,451 individual cells obtained from 62 tumors in 56 patients with pancreatic ductal adenocarcinoma. Six participants also provided tumor samples before and after chemotherapy, making it possible to compare treatment-related changes.

Clones within a single tumor

Single-cell analysis showed that one tumor can contain approximately two to 11 different clones — populations of cancer cells with similar genetic traits. Some of these clones acquire properties that help them withstand anticancer therapy, while others better infiltrate surrounding tissues and spread through the body.

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Previously, cells of this type of cancer were mainly divided into classical, less aggressive cells and basal, more aggressive cells. The new data indicate that genetic changes within individual tumors may enable cells to transition between these states. The authors also linked differences in DNA copy number to the types of cells present in tumors. In cells with pronounced basal features, the researchers recorded increased MYC activity.

Potential targets for therapy

After MYC suppression, basal cells not only shifted toward a classical state but also became more accessible to immune cells. The authors emphasize that further research is needed to assess the therapeutic potential of this approach.

Some clones also demonstrated higher activity of the TIGIT gene and, at the same time, lower activity of PD1. According to the researchers, this may explain the limited effectiveness of PD1-targeted immunotherapy in pancreatic cancer. According to study co-author Aristotelis Tsirigos, clinical trials of drugs that suppress MYC or TIGIT are already underway for ductal adenocarcinoma and other types of cancer.