For the first time, scientists at the Sanford Burnham Prebys Medical Discovery Institute have demonstrated that blocking “cell swallowing” or macropinocytosis in the thick tissue surrounding pancreatic tumors slows tumor growth. An important therapeutic target.The study was published in Cancer detection, Journal of the American Association for Cancer Research.
“Since macropinocytosis has been found to” resurrection “in both pancreatic cancer cells and surrounding fibrous tissue, blocking the process can result in” double distress “in pancreatic tumors.” Said Dr. Cosimo Commisso, an associate professor. Co-director of the Sanford Burnham Prebys Cancer Cell and Molecular Biology Program and senior author of the study. “Our lab is investigating several candidate drugs that inhibit macropinocytosis. This study provides the rationale for the need to proceed as soon as possible.”
Pancreatic cancer remains one of the most deadly cancers. According to the American Cancer Society, only one in ten survives for more than five years, and its incidence is increasing. Pancreatic cancer is projected to be the second leading cause of cancer-related deaths in the United States by 2030.
“If we want to create a prosperous world for all people diagnosed with pancreatic cancer, we first need to understand the key drivers of tumor growth,” said Chief Science Officer, Pancreatic Cancer Action Network. Dr. Linmatrician said. (PanCAN), was not involved in the research. “This study suggests that macropinocytosis is an important target for drug development and that advancing this new therapeutic approach may help more people survive pancreatic cancer. . “
Pancreatic tumors are surrounded by an unusually thick layer of interstitium, or connective tissue, such as glue that holds cells together. This stromal barrier makes it difficult for treatment to reach the tumor and promotes tumor growth by providing nutrients to the tumor. Previous studies by Commisso have shown that rapidly growing pancreatic tumors acquire nutrients through macropinocytosis, an alternative pathway that normal cells do not use. He also wondered if stroma macropinocytosis could also promote tumor growth.
To test this hypothesis, Commisso and his team have surrounded and nourished macropinocytosis of pancreatic tumors called pancreatic cancer-related fibroblasts (CAFs), modified cells and pancreatic tumor cells. Was simultaneously transplanted into mice. Scientists have found that macropinocytosis slows tumor growth in these mice compared to controls that remained active in stroma. This suggests that this approach is a promising way to treat pancreatic cancer.
“I’m excited about this approach because it only blocks the process of promoting tumor growth, instead of removing the stroma that causes the tumor to spread throughout the body,” said Dr. Yijuan Zhang, a postdoctoral fellow. First author of Comisolab and research. “It also decoded the molecular signals that promote stroma macropinocytosis and provided a new therapeutic tool for pancreatic cancer researchers to explore.”
Identified promising drug discovery target
Based on their ongoing macropinocytosis research, scientists have identified potential targets for many drugs that may interfere with the process. Supported by the findings of this study, they will continue to investigate the promising drug candidates that inhibit macropinocytosis as a potential treatment for pancreatic cancer.
“We already knew that macropinocytosis was a very important growth driver for pancreatic cancer and tumors of the lung, prostate, bladder and colon,” said Commisso. “This study further stimulates our efforts to advance drugs that target macropinocytosis, which is necessary to ultimately end many deadly and catastrophic cancers. It can be a breakthrough. “