Vulnerability of cancer cells points to potential treatment path for aggressive disease

Unraveling the unique characteristics of cancer cells and finding less harmful ways to stop their growth have long been the focus of researchers around the world. New results, reported in Nature communications, describe the discovery of a unique dependence of cancer cells on a particular protein, which could lead to desperately needed treatment for hard-to-treat cancers.

The publication concludes a series of groundbreaking studies published in Nature reviewed over the past month by members of a powerful international research collaboration.

Lead author and University of Vermont Cancer Center (UVM) researcher Jason Stumpff, Ph.D., has spent more than two decades studying how cells divide and how errors in this process contribute to diseases such as cancer. His recent work has improved our understanding of the role of a protein called KIF18A in cell division. In these new studies, Stumpff’s lab demonstrates that cancer cells, with the type of abnormalities seen in aggressive tumors, are more dependent on KIF18A for growth than normal cells. This vulnerability in cancer cells could be a potential target to interrupt the growth of cancer cells, as researchers have demonstrated in triple negative breast cancer and colorectal cancer cells.

These findings mark a milestone in a long research journey that began with the support of an American Cancer Society Institutional Research Grant Pilot Fellowship through the University of Vermont Cancer Center and then led to funding from Susan G. Komen and the National Institutes of Health (NIH). . Stumpff, associate professor of molecular physiology and biophysics at UVM’s Larner College of Medicine, decided to publish his team’s findings early, through an open access preprint. This has led to international collaboration with teams from Tel Aviv University, Israel, and the Boston University School of Medicine. Each team studied the genes necessary for the growth of tumor cells containing an abnormal number of chromosomes (the threadlike structures that carry the genetic information of a cell) in order to identify new therapeutic targets.

Stumpff is an expert in the mechanical control of cell division and the aspects of this process that contribute to the development of diseases such as cancer. His colleagues at Tel Aviv University were studying aneuploidy – which occurs when one or more chromosomes are added or removed after cell division – and the partners at Boston University have focused on complete genome duplication. , where a complete set of duplicate chromosomes are found in a daughter cell after division.

The role of KIF18A was found to be important in the work of each team and contributed to a clearer and broader picture of its role and importance in stopping the growth of abnormal tumor cells. Early sharing of knowledge and unpublished data, as well as collective troubleshooting of questions and verification of results, was essential to the groups’ series of findings. Their efforts have yielded good results – three publications in Nature and Nature communications report revolutionary discoveries that could contribute to more targeted and less harmful drug treatments for certain cancers.

A confluence of open data sharing, the participation of clinical experts and cancer patients and the exploitation of a collaborative approach have been key elements in the success of this research, notes Stumpff.

“The collective impact of this research collaboration illustrates the importance of sharing data and improving the rigor of scientific studies to effectively advance the discovery of basic science towards significant progress in the fight against cancer” , says Stumpff. “This work has the potential to improve approaches to treating patients in the future – and we are excited to take it forward.

Provided by the Larner College of Medicine, University of Vermont