Spurring Collaboration to Combat Metastatic Colon Cancer

Bringing together expert scientists and clinicians with a singular focus — to develop new and effective treatments to improve a bleak prognosis — is the aim of Cleveland Clinic’s new Research Center of Excellence in Colon Cancer Metastasis.

“We have very poor treatments for metastatic colon cancer, basically variations on 5-fluorouracil. That was discovered 50 or 60 years ago,” said Emina Huang, MD, a colorectal surgeon and Co-Director of the new center. “We haven’t had that many advances since that have been successful.”

Colorectal cancer is the third most common cause of cancer deaths in the United States. The five-year relative survival rate for stage IV colon cancers is approximately 11 percent, and 12 percent for stage IV rectal cancers, according to the National Cancer Institute’s Surveillance, Epidemiology, and End Results database.

“We saw the need nationwide, and internationally, to try to address this deadly form of colon cancer,” Dr. Huang said. So she, her colleague and Co-Director Xiaoxia Li, PhD, an immunology researcher, and others sought support from Cleveland Clinic to launch the new center.

The Research Centers of Excellence program, administered by the Lerner Research Institute, matches basic, translational and clinical researchers at various Cleveland Clinic institutes who share common interests and goals. The intent is to foster team-based, innovative research that challenges existing paradigms and produces new products, methods or technologies.

Funding of as much as $300,000 a year for three years is available and is shared evenly by the partnering institutes. Centers are expected to use funds to build a team that will be competitive for external funding, producing high-impact publications and invention disclosures.

Empathy and expertise

The colon cancer metastasis center’s staffing aligns with Cleveland Clinic Cancer Center’s overall mission to promote interdisciplinary collaboration among the various institutes whose clinicians, surgeons and researchers are involved in cancer treatment.

“We have a really expert, multidisciplinary team that is trying to address this problem from all different angles,” Dr. Huang said. But in addition to uniting specialists, the center’s goal is to cultivate the infrastructure, resources and shared enthusiasm to explore the most promising research advances, she said.

Colorectal surgeons, medical oncologists, a liver surgeon, a pathologist and others will contribute their clinical acumen. Dr. Li’s work on cancer immunology, Angela Ting, PhD’s research on tumor epigenetics, and Paul Fox, PhD’s work on angiogenesis are just a few of the initial, promising research avenues.

The center secured initial funding in February 2016, so it is still too early to know which prevention or treatment avenues will pan out, Dr. Huang said. “Our hope is that one, two or three of our approaches will translate to the bedside. Hopefully we’ll have multiple effective strategies coming out of this.”

Exploring multiple avenues

Metastatic colorectal cancer’s complexity warrants a multipronged search for targeted treatments that will work for individual patients. Immuno-oncology holds great promise, but more work is needed to identify effective applications in metastatic colon cancer, Dr. Li said. Dr. Ting will continue to explore tumor epigenetics, including significant differences between primary colon cancer and metastatic tumors. Dr. Fox recently discovered a novel, potent antiangiogenic factor, vascular endothelial growth factor-Ax (VEGF-Ax), which could be a therapeutic agent and whose unintended diminution by VEGF-A-targeted therapies may exacerbate the growth of metastatic colorectal tumors.

Dr. Huang plans to explore the potential role of inflammation in the stroma and how stem cell therapy could improve treatment of metastatic colon cancer patients. Other research will assess how to manipulate the tumor microenvironment and/or the colon microflora to prevent or suppress the development of metastatic disease. The center’s additional team members include Matt Kalady, MD, Cristiano Quintini, MD, Alok Khorana, MD, and Thomas Plesec, MD.

“This team comprises the best of the best in colorectal cancer research at Cleveland Clinic. We have multiple approaches to attack this,” said Dr. Huang, who is both a researcher and a clinician. She spends an estimated 40 percent of her time caring for patients. “I see this disease, and that is what really tugs at me,” she said.

Picking up the pace

The center aims to accelerate research so that it translates more quickly to the bedside. Having expertise and resources in a single setting “means we can act immediately and investigate all promising leads,” Dr. Li said. Previously, researchers had to wait for external funding for most projects, which can add months or years to the discovery process. “Now we can develop these new research directions right away,” she said.

Another benefit of blending the research and clinical worlds is that researchers gain easier access to patient tissue samples to facilitate their work. For example, Cleveland Clinic surgeon Federico Aucejo, MD, maintains a liver tissue biobank whose inventory includes tumor samples of liver metastases from colorectal cancer. The hope is that a greater understanding of both primary and metastatic tumors will emerge from investigations involving patient epithelial cells, organoids, xenograft modeling and more.

“We have some preliminary data on expression profiles between normal and colon cancer tissues,” Dr. Li said. “We have some exciting candidates that we want to pursue.”

Paying it forward

Referring physicians can counsel patients with metastatic colon cancer that the new center aims not only to help them, but to advance the entirety of knowledge about metastatic colon cancer to help others as well.

“In three to five years we’d like to have a defined goal and a number of projects ready to attract funding from the National Institutes of Health, cancer societies or other funding sources at the national level,” Dr. Li said. “Hopefully we can develop some new therapeutic approaches for the treatment of metastatic colon cancer. That’s the goal.”

“I would love it if we can be at phase I with one of our discoveries by then,” Dr. Huang said. “We’re really enthusiastic and energized by this center’s formation. Together we’ll be able to do something amazing.”