Bad Company: What’s Around a Tumor Might Help It Grow Back

Newswise — Gregory Gan, MD, PhD, doesn’t just study cancer cells to find out why they regrow and spread; he also studies their surroundings. Called the tumor microenvironment, cells around a tumor create the scaffold in which the cancer cells live. Gan thinks the tumor microenvironments may help head and neck tumors to regrow after radiation therapy or chemotherapy and to spread to other places in the body. Gan is using a two-year $150,000 grant from the Radiological Society of North America Research and Education Foundation to study the tumor microenvironment of head and neck cancers. Although he received the grant in July, he was recognized at the annual 2015 RSNA meeting in December.

The American Cancer Society estimates that more than 60,000 people will receive a diagnosis of cancer in their head or neck this year. “Traditional therapies like surgery, chemotherapy and radiation make up the backbone of head and neck cancer treatment. However, in almost 30 years, we haven't made many breakthroughs and overall survival at five years is around 25 percent,” says Gan. Smoking and drinking cause most head and neck cancers. But people whose head and neck cancers are caused by human papillomavirus tend to have much better survival rates than people with HPV-negative cancers. Gan wants to know why.

Gan studies a particular change cells can go through called epithelial-mesenchymal transition. Epithelial cells line the surface of organs, tissues and the outside of skin. These cells can multiply quickly and are sensitive to radiation and chemotherapy. Mesenchymal cells support other cells and don’t multiply quickly. Instead, they can resist some types of chemotherapy and radiation and can invade surrounding tissues. Scientists think that chemotherapy, radiation, or inflammation can transform some cancer cells from an epithelial type to a mesenchymal type. They think that undergoing this change may explain why some cancers, including head and neck cancers, can resist radiation therapy and chemotherapy.

Gan studies a particular set of biochemical changes in cells, called the ‘hedgehog’ pathway. The hedgehog pathway helps cells in the embryo to grow body tissues at the very beginning of life. It’s also important for healing tissues in adults. But, this pathway causes tumor cells and support cells called fibroblasts to transform into mesenchymal cells.

Gan is studying how the hedgehog pathway can cause cancer cells to transform into mesenchymal cells and regrow after chemotherapy or radiation therapy. Gan has found that after chemotherapy and radiation therapy, the hedgehog pathway becomes more active in fibroblasts in the tumor microenvironment. These activated fibroblasts may allow cancer tumors to grow back. “I’m finding that if you inhibit the hedgehog pathway, you may be able to block the ability of the tumor to reestablish itself,” he says.

To study how tumors regrow, Gan will use tumor tissue generously donated from actual patients. He plans to study how these tumors grow with and without radiation-treated fibroblasts. He will also study the proteins these fibroblasts secrete to enable tumors to resist traditional therapies. And, if possible, he will begin to design new drugs that can block those proteins to make tumors respond more to radiation and chemotherapy.

Gan hopes that one day these findings will translate into human clinical trials at UNM. “The whole point of this research, at the end of the day, is to make chemotherapy and radiation therapy more effective,” Gan says, “so that we can improve cure rates for this dismal disease.”

About Gregory Gan, MD, PhDGregory Gan, MD, PhD, is an Assistant Professor in the Department of Internal Medicine, Division of Hematology/Oncology, Section of Radiation Oncology, at the University of New Mexico School of Medicine. Trained as a radiation oncologist, his research focuses on the tumor microenvironment and Hedgehog pathway, which is involved in the epithelial-to-mesenchymal transition. This pathway appears to enhance tumor radioresistance, invasiveness, and metastasis and inhibiting this pathway could lead to improvement in cancer control in head and neck cancers in addition to several other cancers. Dr. Gan is a member of the American Society of Therapeutic Radiation Oncology, the American Board of Radiology and the American Medical Association. He has written multiple peer-reviewed research publications, book chapters, and abstracts, on various topics in cancer biology and radiation oncology.

About the GrantRadiological Society of North America Research and Education Foundation supported the research reported in this publication under Award RSNA Scholar Grant 2015-2017, Principal Investigator: Gan, Gregory. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Radiological Society of North America.

About the UNM Comprehensive Cancer CenterThe University of New Mexico Comprehensive Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated Cancer Center in a 400-mile radius. One of the premier cancer centers nationwide, the UNM CCC has 128 board-certified oncology physicians, forming New Mexico’s largest cancer care team. It treats about 60 percent of adults and virtually all the children in New Mexico diagnosed with cancer — more than 10,000 people— from every county in the state in more than 135,000 clinic visits each year. Through its partnership with the New Mexico Cancer Care Alliance, an “exemplary national model for cancer health care delivery,” the UNM CCC offers access to more than 160 clinical trials to New Mexicans in every part of the state. Annual research funding of more than $72 million supports the UNM CCC’s 132 cancer scientists. Working with partners at Los Alamos and Sandia National Laboratories, Lovelace Respiratory Research Institute, and New Mexico State University, they have developed new diagnostics and drugs for leukemia, breast cancer, ovarian cancer, prostate cancer, liver and pancreatic cancer, brain cancer, and melanoma; garnered 33 new patents and 117 patents pending; and launched 13 new biotechnology companies since 2010. Learn more at cancer.unm.edu.