揭开软组织肉瘤的基因分子之谜

Scientists at Joslin Diabetes¹ Center in Boston have uncovered important molecular² and genetic⁴ keys to the development of soft-tissue sarcomas（肉瘤） in skeletal（骨骼的） muscle, giving researchers and clinicians additional targets to stop the growth of these often deadly tumors. Published in the Proceedings⁶ of the National Academy of Sciences, the study identified two major molecular signaling pathways (the Ras and mTOR pathways) that are common in tumor⁵ growth and development. These molecular pathways regulate cell growth and division, two cellular⁷ properties whose over-activation are hallmarks（特点，品质证明） of cancer biology.

"In humans, some sarcomas respond to chemotherapy, says lead author Amy J. Wagers⁸, PhD, an associate professor of stem cell and regenerative biology at Harvard Medical School and Joslin Diabetes Center, "but many don't. With these findings, we have vetted⁹ a list of new candidate targets whose inhibition may lead to regression of these tumors."

Many soft-tissue sarcomas, which develop in certain tissues such as bone and muscle, carry specific genetic mutations or unique gene³ signatures, which can allow scientists to develop more precise, targeted therapies. Wagers and her colleagues engineered a tumor system in mice by introducing into mouse skeletal muscle a cancer-carrying gene, or oncogene（致癌基因） , known to cause tumors in humans. They used this engineered system to identify a small set of genes¹⁰ that are active in sarcoma tumors.

There are many different types of soft-tissue sarcomas, which develop in tissues that connect, support or surround other structures and organs, including muscle, tendons（肌腱） , nerves, fat and blood vessels¹¹. If diagnosed early, treatment, primarily through surgical¹² removal of the tumor, radiation therapy or chemotherapy, can be effective. If the tumor has spread, however, the tumor can be controlled only for a period of time, but treatment does not often cure the disease.

By inducing these tumors in mice, Wagers says the scientists knew when the tumors would form in the mice and where in the body they would develop, which helped them better understand the molecular and genetic pathways underlying¹³ the disease. With this knowledge, researchers may be able to develop new intervention¹⁴ strategies that interfere¹⁵ with these genetic activities and stop the growth of this type of tumor.

"With the engineered system we developed, we can find new fragile points in the tumor to target," says first author Simone Hettmer, MD, a pediatric（小儿科的） oncologist at the Dana-Farber/Children's Hospital Cancer Center, who treats children with these tumors. In addition, she adds, the system allows scientists to look at the genetic changes in sarcomas and how they interact with the development of tumors and can be applied¹⁶ to sarcomas in tissues other than skeletal muscle.