In a study published Thursday, researchers at UC San Diego School of Medicine identified new therapeutic targets that could lead to treatment options for patients with gastrointestinal stromal tumors.
Gastrointestinal stromal tumors are a subtype of cancers known as sarcomas. GIST is the most common type of sarcoma, with approximately 5,000 to 6,000 new patient cases annually in the United States. GIST cannot be cured by drugs alone, and targeted therapies are only modestly effective, with a high rate of drug resistance.
The study, published in Thursday’s online edition of Oncogene, found that specific cell-to-cell communication influences GIST biology and is strongly associated with cancer progression and metastasis.
The researchers discovered that certain GIST cancer-associated fibroblasts — a cell population within GIST tumors — can communicate with GIST cells. This crosstalk between the cells results in more aggressive tumor biology.
“By examining the tumor micro-environment of GIST, we were able to look at a previously unrecognized cellular target for GIST therapy that could result in improved disease control and cure rates,” said senior author Dr. Jason Sicklick, professor of surgery at UCSD School of Medicine and surgical oncologist at UCSD Health. “It’s a paradigm shift for the field.”
Approximately half of patients with metastatic GIST will develop drug resistance within 20 months of starting first-line therapy. Once the first line of treatment for GIST loses effectiveness, response rates to subsequent therapies also dramatically decline. Thus, said the authors, combination therapies against multiple cellular targets, such as CAFs, could be more effective, especially before the disease has metastasized.
GISTs develop from nerve cells in the wall of the gastrointestinal tract and can occur anywhere from the esophagus to the rectum. These tumors most commonly occur without telltale symptoms, such as feeling full sooner than normal after eating or abdominal pain. Occasionally, symptoms include gastrointestinal bleeding or signs of intestinal obstruction. GIST cases most often develop and are diagnosed in persons age 50 and older.
The researchers said next steps include investigating drug combinations for CAF-targeted therapies.
“We have to start thinking outside of the box. We’ve been using
bigger and bigger hammers to hit the same target and not seeing different
results,” said Sicklick. “We need to start hitting a different target. Our
study results could be the first insights into a new approach.”