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A collaboration between Dr. Jedd Wolchok, the Meyer Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, and Dr. Yelena Janjigian, chief of the gastrointestinal oncology service at Memorial Sloan Kettering Cancer Center, is looking to transform the care of gastroesophageal cancer (GEC) patients with untreatable disease – earning the pair a grant from Stand Up To Cancer® (SU2C) as a part of the SU2C-Torrey Coast Foundation Gastroesophageal Cancer Dream Team Collective. Dr. Wolchok and Dr. Janjigian garnered one of only three team designations for SU2C’s most recent award.

Fighting a Formidable Foe

Gastrointestinal cancer accounts for one in four cancer diagnoses and one in three cancer-related deaths worldwide, according to the World Health Organization’s International Agency for Research on Cancer. And yet the disease is resistant to treatment, Dr. Janjigian said. Up to 70 percent of GEC patients don’t respond to existing treatments, so looking for innovative drugs and regimens is imperative to changing these statistics. That’s why Dr. Janjigian approached Dr. Wolchok – a medical oncologist who focuses on metastatic melanoma and other skin cancers – to work together on a SU2C grant, she said.

“For this particular grant, there was strength in his immunotherapy and immune monitoring experience,” she said. “For characterizing the samples, but also potentially developing future therapeutic strategies.”

As part of their work, the two preeminent cancer researchers are working on a new clinical trial therapy to boost the success rate of treatment for metastatic HER2-negative and HER2-positive GEC disease.

Dr. Wolchok, Dr. Janjigian and their teams are building on previous research that showed promise for long-term survival when patients were treated with the combination of an immune checkpoint blockade (ICB) and chemotherapy. That research’s success was limited, however, since most patients did not respond to the combined treatment because of chromosomal instability (CIN), the gain or loss of entire segments of chromosomes that can occur in cancer. CIN is also associated with movement of the body’s immune cells from the blood into a tumor, known as lower intratumoral T cell infiltration, which can lead to lower response rates to ICB treatment and worse overall survival.

The three-year SU2C grant will help the physician-scientists investigate mechanisms of immune evasion and suppression in GEC, focusing on those caused by and related to chromosomal instability. Today, the team is in the early stages of research, Dr. Wolchok said. “We’re assembling datasets. Putting tumor specimens together for whole genome sequencing of the tumors to see if we can identify which targets the immune system may be seeing in some of these patients,” he said. “It’s exciting for us to apply the techniques that we developed studying one cancer and really expand on that in other ways.”

The Immunotherapy Connection

Dr. Wolchok first started working with Dr. Janjigian in 2014 when she called him to ask questions about an immunotherapy that he developed.

“She said, ‘I would like to understand more about why they work in some people with stomach cancer and not in others, and what we need to combine them with to get even better response,’” he said. “It was an organic way for us to work together. She being an expert clinical trialist in gastric cancer came to me—someone who studies the immune response to cancer in the various different kinds of cancer, both in the clinic and in the laboratory.”

The current SU2C project is the third Dream Team that Dr. Wolchok has been a part of. His first two teams in 2013 and 2015 focused on immunotherapy and lung cancer, respectively. SU2C programs appeal to Dr. Wolchok because he gets to collaborate with others, he said.

“One of the things about Stand Up To Cancer that I really like is its focus on team science,” he said. “These grants only go to groups of investigators. That speaks to the importance of collaboration—that we need to come out of our silos and appreciate the different ways to look at a specific cancer problem. Being able to work with experts who look at the same problem through different lenses is very valuable, and gives more meaning to the research.”

Dr. Janjigian is also impressed with the possibilities of collaboration between different organizations, especially those as large and well-respected as MSK and Weill Cornell Medicine, she said.

“The Stand Up To Cancer opportunity really highlights being able to leverage larger data sets and being a global principal investigator and having large clinical trials. We have access to a lot more biomarker data [as part of this SU2C grant] and that helps drive the next generation of studies and ideas,” she said.

Dr. Wolchok agrees. “Stand Up To Cancer’s focus on team science really allows for mechanism-driven research to be conducted. Their short timescale makes certain that you actually accomplish something,” he said. “It's just a real privilege to be part of this process.”