Weizmann Institute of Science: Knowledge researchers gathered on cancer ‘can be harnessed for developing new drugs’

A study by scientists from the Weizmann Institute of Science in Rehovot, Israel, has focused on cancer cells’ “bullying” behavior and its effect on cells in a tumor’s microenvironment.

In particular, the new study published in Nature Communications, led by Dr. Ruth Scherz-Shouval of the Weizmann Institute of Science, found that mutations in BRCA genes “known for their role in breast and ovarian cancer, adversely affect a major subset of cells in the microenvironment of pancreatic cancer,” according to Weizmann Wonder Wander. That can impair “the body’s anticancer immune response.”

“The treatment of cancer has been revolutionized in recent years with the introduction of immunotherapy -- drugs that recruit the immune system in a targeted attack on cancer cells,” Scherz-Shouval said, according to Weizmann Wonder Wander. “Hopefully, the knowledge that we and other researchers have gathered -- including the identification of immune-response-suppressing fibroblast subtypes, and of the proteins involved in turning fibroblasts into cancer promoters -- can be harnessed for developing new drugs. Such drugs, alongside immunotherapeutic treatments, would effectively target not only cancer cells, but also their collaborators.”

In the study, the largely incurable, aggressive pancreatic ductal adenocarcinoma was studied.

“Only 10% of those diagnosed with it survive more than five years after diagnosis,” Weizmann Wonder Wander said. “Previous studies had shown that in this malignancy, cancer cells succeed in rewiring and even changing the structure and function of certain cells, called fibroblasts, in their microenvironment.”

Fibroblasts, which are basic components of each organ in a body, account for up to 90% of tumor tissue in pancreatic cancer.

“Once these cells cross over to the cancer’s side, they are reprogrammed into different subpopulations of cancer-associated fibroblasts,” Weizmann Wonder Wander said. “However, it is still largely unknown whether different cancer-related mutations, such as those in the BRCA genes, lead to different types of fibroblast reprogramming.

Dr. Lee Shaashua Berger, one of the researchers from Scherz-Shouval's group, commented on the findings.

“We were amazed to discover that the presence of BRCA mutations in cancer cells triggered changes in neighboring fibroblasts, even though the fibroblasts themselves did not carry the mutation," Berger told Weizmann Wonder Wander. "These altered fibroblasts, in turn, started suppressing the immune system's T cells, providing a favorable environment for cancer progression.”

“This study highlights the intricate interactions between cancer cells and their surrounding microenvironment," Dr. Aviad Ben-Shmuel, another researcher from the Weizmann Institute, told the website. “Understanding how cancer cells 'persuade' neighboring cells to aid in their proliferation opens new avenues for targeted therapies that can disrupt these interactions and enhance the body's natural defenses against cancer.”

Another study emphasized the role of epigenetics in fibroblast conversion into cancer-promoting cells. The separate study conducted by “Coral Halperin from Scherz-Shouval's lab, in collaboration with Dr. Joschka Hey from Professor Christoph Plass's lab at the German Cancer Research Center,” revealed that cancer cells induce epigenetic alterations in normal fibroblasts, leading to changes in gene expression and the production of cancer-assisting proteins.

The Weizmann Institute of Science researchers -- including Dr. Gil Friedman, Oshrat Levi-Galibov, Debra Barki, Dr. Reinat Nevo, Yaniv Stein, Lior Chen, Shimrit Mayer, Roni Stok, Hend Bishara, and Rawand Hamodi from the Biomolecular Sciences Department -- helped in the study of pancreatic cancer microenvironment changes.

Additional collaborators from such institutions as Memorial Sloan Kettering Cancer Center in New York, Boston University, Weill Cornell Medicine in New York, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Sheba Medical Center, Tel Aviv University and Cold Spring Harbor Laboratory in New York contributed to the research.