Why two scientific powerhouses are teaming up to tackle rare cancers long overlooked in research

As a medical school student, oncologist Vinod Ravi felt like he understood what it took to treat disease. Then his brother was diagnosed with a very rare form of bone cancer, a reality check on the limitations of not only his own education, but the entire field of rare cancer research.

Ravi combed through the research and treatment protocols for Ewing’s sarcoma, the cancer his brother had been diagnosed with, but found them patchy and outdated. The drugs to treat the disease fell far short, and Ravi’s brother passed away.

“It was really a big slice of Swiss cheese with so many holes in it that it still needs a lot of work,” said Ravi, an oncologist at the University of Texas MD Anderson Cancer Center who specializes in treating sarcomas.

Now, Ravi’s colleagues at MD Anderson are looking to address those gaps by partnering with the Broad Institute of MIT and Harvard on a new translational research platform focused on rare cancers. A cancer is deemed rare if there are fewer than 40,000 cases a year, but cumulatively, rare cancers account for about one-quarter of all cancer cases and cancer deaths. The new collaboration, launched this year, aims to use cells pulled from patient tumors to develop novel models of the disease and use them to systematically map potential genetic and pharmacological vulnerabilities in the cancers.

“This partnership brings together two world-renowned institutions with very complementary expertise,” said Tim Heffernan, a cancer biologist and and executive director of MD Anderson’s cancer research platform TRACTION. The center, which diagnoses and treats more than 5,000 rare cancer patients each year, launched the Rare Tumor Initiative in 2019 to build up a catalog of rare cancers that they hope may one day lead to new therapeutics. They’re able to use that catalogue as a starting point to develop new cancer cell lines that can be used in research.

But despite MD Anderson’s catalog of cancer cells and extensive experience, researchers interested in developing new treatments for rare cancer still run into the “same challenges that the field is running into — we don’t have necessarily the models to evaluate these new insights,” Heffernan said.  “We really need new translational platforms that allow us to translate what we’re learning from the Rare Tumor Initiative to innovate around new clinical trials.”

That gap makes for a “quite natural” partnership with the Broad Institute, according to William Sellers, director of the Broad’s Cancer Program, which has already developed tools that can help make use of the Rare Tumor Initiative’s work. That includes the Cancer Cell Line Factory, which aims to collect and then convert tumor samples into cell models. These models can then be fed into the Broad’s Cancer Dependency Map, a project that can analyze the models to detect genetic and pharmacologic vulnerabilities in a tumor that could pave the way for new therapies.

One of the cell lines being used to develop a rare cancer cell model came from a patient named Quinton Maynard, who was treated by Ravi and other providers at MD Anderson after being diagnosed with a cardiac angiosarcoma, a rare cancer that occurs in the heart.

“Even before the cancer diagnosis. We were already all terrified. And then to hear that it likely was cancer, you know, it’s just layer upon layer upon layer of bad news for quite a while,” said Easter Maynard, Quinton’s sister. “I think we all felt just completely overwhelmed and underwater because it was like every time you try to stand back up, you get knocked down again with another wave of bad information.”

Quinton’s cancer spread. In the final weeks of his life, Hurricane Harvey hit the area, and his family worried, as water levels climbed, that they wouldn’t be able to get him to a hospital in case of emergency. His lymphatic issues were creating painful swelling across his body. But he “really managed to smile,” his sister remembered, hunkering down in the storm and watching Disney movies with his kids.

“He wasn’t ready to give up even when his body was; his spirit was still strong,” said Easter.

Quinton Maynard passed away in September 2017 at age 38, five years after his diagnosis. It was far more time than his family expected, given that the median survival of a patient with metastatic cardiac angiosarcoma is roughly six to seven months.

Ravi said that during his years of treatment, Maynard made it a point to read up on and remain at the cutting edge of possible treatments for his cancer. Although “a lot of it was research, which doesn’t really impact his clinical care, he was still very committed to supporting that while he was alive,” said Ravi.

He also agreed for his cancer cells to be gathered and used for research, which is how they made their way into MD Anderson’s tumor catalogue.

“His cells are still alive in the laboratory and we are still actively working on it, even though he’s long gone,” Ravi said.

The Broad’s Sellers is hopeful that the new research platform will allow researchers to use cells like those donated by Maynard to find new therapeutic targets for rare cancers. There’s been “no real movement on the therapeutic front over the last decade,” Sellers said.

Even if the research does not turn up new targets, Sellers said it could enable research to evaluate whether existing therapeutics could work against any of the new cell lines from the collaboration.

Ravi said that when both his brother and Quinton Maynard were diagnosed with cancer, the field of rare cancer was somewhat at a standstill all the while suffering from significant unmet need. The scarcity of rare cancer cases limited the cell lines that could be grown and researched, and modern, robust tools had previously not been used to develop the requisite cell models to test rare cancer therapies on. He said that’s due, in part, to a lack of incentives for pharmaceutical companies to invest money into researching, developing, and producing drugs for clinical use.

He’s hopeful the collaboration between MD Anderson and the Broad will give rare cancers a far greater level of attention and resource allotment.

“I think we all have to look inward,” Ravi said. “Let’s build that efficacy, and then they will come. Just asking people for drugs doesn’t help. You have to prove to them that it will be successful, and it’s impossible to do that without the kind of work that MD Anderson is currently doing with the Broad.”