Scientists at the Sanford Burnham Prebys Prebys Medical Discovery Institute showed for the first time that preventing “cell drinking,” or macrocytosis, in the thick tissue surrounding a pancreatic tumor slows tumor growth – providing more evidence that macrocytosis is a driver of pancreatic cancer growth and is a cause An important therapeutic goal. The study was published in Cancer detection, Which is the journal of the American Association for Cancer Research.
Says Cosimo Comiso, Ph.D., associate professor and co-director of the Cancer Molecular and Cellular Biology Program at Sanford Burnham Prebis and senior author of the study. “Our laboratory is examining many candidate drugs that suppress macrocytosis, and this study provides the rationale for developing them as quickly as possible.”
Pancreatic cancer remains one of the deadliest types of cancer. Only one in ten people live for more than five years, according to the American Cancer Society, and the incidence is increasing. Pancreatic cancer is expected to be the second leading cause of cancer-related deaths in the United States by 2030.
“If we want to create a world in which all people diagnosed with pancreatic cancer thrive, we first need to understand the key drivers of tumor growth (Pancan), which was not involved in the study,” says Lynn Matrician, PhD, chief science officer for the Pancreatic Cancer Network. “This study indicates that macrocytosis is an important target for drug development, and that advances in this new therapeutic approach may help more people survive pancreatic cancer.”
Starve in vain
Pancreatic tumors are surrounded by an unusually thick layer of stroma, or the glue-like connective tissue that holds cells together. This meaty barrier makes it difficult for treatments to reach the tumor, and fuels tumor growth by providing the tumor with nutrients. Previous research by COMESO showed that fast-growing pancreatic tumors obtain nutrients through granulocytosis, an alternative route that normal cells would not use – and he wondered if the macrocytosis in the stroma might fuel tumor growth as well.
To test this hypothesis, Komiso and his team prevented macrocytosis in the cells that surround and nourish pancreatic tumors, called pancreatic cancer-associated fibroblasts (CAFs), and transplanted modified cells with pancreatic tumor cells into mice. The scientists found that tumor growth was slowed in these mice – compared to control groups in which macrocytosis remained active in the stroma – indicating that this approach holds promise as a method of treating pancreatic cancer.
“We are excited about this approach because instead of removing the stroma, which can cause the tumor to spread throughout the body, we are simply blocking the process that drives tumor growth,” says Yijuan Zhang, PhD, postdoctoral researcher at the Komiso Laboratory and first author of the study. . “We have also decoded the molecular signals that drive macrocytosis in the stroma, providing new treatment avenues for pancreatic cancer researchers to explore.”
Setting promising drug targets
Based on ongoing macrocytosis research, scientists have identified several drug targets that may inhibit this process. Supported by the results of this study, they will continue to investigate the promise of candidate drugs that suppress macrocytosis as potential treatments for pancreatic cancer.
“We already knew that macrocytosis was a very important driver of the growth of pancreatic cancer, as well as lung, prostate, bladder and colon tumors,” says Comiso. “This study stimulates our efforts to develop a drug that targets macrocytosis, which may be the breakthrough we need to put an end to many deadly and devastating cancers.”
Additional study authors include Victoria Recofro, Michael Jung, Quinn Mo Galencamp, Olga Zagnetko, and David A. Scott of Sanford Burnham Pribes; Yeonbo Lee and Andrew M. Lowe from the University of California, San Diego.
Study DOI is 10.1158 / 2159-8290.CD-20-0119.
The research presented in this press release was supported by the National Institutes of Health (NIH) (CA207189, CA211036, and P30CA030199).
About Sanford Burnham Prebes Medical Research Institute
Sanford Burnham Prebys is a prominent, independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to deeply affect human health. For more than 40 years, our research has produced breakthroughs in cancer, neuroscience, immunology, and pediatric disease, anchored in the National Cancer Institute designated cancer center and advanced drug discovery capabilities. For more information, visit us on SBPdiscovery.org or on Facebook at facebook.com/SBPdiscovery and on Twitter. Embed a Tweet.