• Dr. Robert A. Nagourney, MD

Do The Mutations That Drive Cancer Actually Affect Immunity?

A study in the journal Oncogene finds that pancreatic cancer may progress as a result of the loss of normal immune response. (source: Datta, J et al Oncogene, 2022; 41:3640-54)

  • Cancer-associated oncogenes KRAS and TP53 are mutated in 90% of pancreatic cancers

  • It has long been thought that these mutations “drive” the tumors.

  • Dr. Datta and coinvestigators show these mutations may actually cooperate to alter the the immune environment that subsequently allows cancers to progress.

  • By recruiting a subset of white blood cells to infiltrate the pancreatic tissue, the cancer cells assume an entirely different behavior... to become more aggressive and resistant to therapy.

The findings are extremely interesting, as they describe the unpredictable complexity of human cancer. While pharmaceutical companies and scientific investigators work to develop drugs that selectively target mutated TP53 and KRAS, is it possible that other, more global factors including immune infiltration, cell protein expression and the cross-talk between cancer cells and our immune system, actually characterize tumor behavior?

This could have far-reaching implications for therapeutics, as targeting KRAS and TP53 as isolated mutations may not influence the observed immune dysregulation.

I applaud these investigators for their expansive approach to cancer biology and for exploring cancer systems rather than cancer cells. Our laboratory’s use of specimens derived directly from surgical biopsies is very similar as we use cancer cells in their own native environment to explore how patients’ cancers respond to treatments.

We are only beginning to understand cancer biology and it is time for the reductionist thinkers to accept the fact that cancer is more complicated than genes or mutations alone.

The future of cancer research will rely upon human tumor cultures as the best models for the selection of drugs and the development of new treatments.