A collaboration between researchers from the University of California, San Diego School of Medicine (CA, USA) and Mayo Clinic (MN, USA) have discovered, for the first time, that the hedgehog signaling pathway is fundamental to the development of gastrointestinal stromal tumors (GIST).
These findings, recently published in Oncotarget, provide a novel target for the development of new therapies to treat patients with GIST.
In the United States. GISTs are the most prevalent type of sarcoma, with approximately 6.8 individuals per million diagnosed each year. These tumors are derived from the interstitial cells of Cajal, which are responsible for signaling the muscles in the digestive system to facilitate the movement of food and liquid down the gastrointestinal tract. At the molecular level, GISTs are commonly driven by the KIT oncogene.
Therapeutic programs to treat GISTs usually include the use of progressively more aggressive regimens to beat the growth of tumor cells, which become increasingly more resistant to therapy. However, this strategy is associated with increased toxicity to patients and diminished efficacy; over 95% of patients eventually develop drug-resistant GIST, demonstrating the need for new therapies.
“Our new finding is a step forward in overcoming tyrosine kinase inhibitor resistance, a clinically significant problem in the management of GIST. By knowing that hedgehog signaling is altered in human GIST, and that it controls KIT expression, we may have found a way to turn the cancer off,” commented Jason Sicklick (San Diego School of Medicine).
Continuing studies are looking at the use of arsenic to treat GIST. Sicklick explained: “We are flipping the switch ‘off’ with arsenic, a drug that is already in clinical practice. With this drug, we are able to kill multidrug-resistant cell lines, offering a new approach to treatment.”