Analyzing nearly 500,000 single cells, researchers at the 

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

 are refining how to classify colorectal cancer and identify new targets to develop effective therapies.

, associate professor of medicine at IU School of Medicine, was 

. Ateeq Khaliq, PhD, is the paper’s first author and a postdoctoral fellow in Masood’s lab.

Previously, the research community classified colorectal cancer into four subtypes called consensus molecular subtypes (CMS) – CMS1, CMS2, CMS3 and CMS4. Masood and colleagues found colorectal cancers don’t fit neatly into these discrete subtypes. Instead, these tumors and their ecosystems exist more in a continuum.

Masood and colleagues found common factors across all the CMS subtypes that are associated with poor outcomes for patients. If a patient has higher numbers of certain cell types – cancer-associated fibroblasts (CAFs) and/or tumor-associated macrophages (TAMs) – these patients will not do well. Masood sees these findings as an opportunity to develop better treatment for patients.

“Single-cell analysis is providing a much higher resolution, which was not possible before,” Masood said. “We found that the colorectal cancers are much more complex than these subtypes.”

Single-cell analysis allows researchers like Masood to use technology to investigate cell variation and the different cell types within a cell population, such as a tumor.

In addition to being a gastrointestinal oncologist, Masood has training in bioinformatics and computational biology and does genomic research as a cancer center member.

Researchers analyzed 49,589 single cells from 16 racially diverse colorectal cancer patients, plus seven adjacent normal colon tissue samples. Those cells were then profiled along with data from multiple external cohorts, totaling 487,829 single cells. This data set is among the largest colorectal cancer single-cell atlases to date, Masood said.

“This single-cell analysis is showing that cancer-associated fibroblasts and TAMs predict the poor outcomes; thus, they offer therapeutic targets,” Masood said. “This is the next set of work that we will be doing at IU.”

Researchers are now working on testing if inhibiting those cell types – particularly CAFs that are known to cause resistance to immunotherapy – can provide a path for new colorectal cancer treatments.

“Most colorectal cancer patients still receive chemotherapy, with modest benefit,” Masood said. “There is an unmet need to develop better therapies, so our hope is we can improve clinical outcomes by developing new drug therapies.”

Additional authors from IU School of Medicine are 

, and Yingjie Qiu; and IU Simon Comprehensive Cancer Center members 

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Analyzing nearly 500,000 single cells, researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center are refining how to classify colorectal cancer and identify new targets to develop effective therapies.

IU Cancer Researchers Refining Colorectal Cancer Classification, Identifying New Targets for Treatment Using Cutting-Edge, Single-Cell Technology

Indiana University School of Medicine has announced the hiring of a world-recognized medical oncologist and multiple myeloma researcher to lead the 

, bolstered by a $15 million fund established by the Walther Cancer Foundation to support him in this role.

Kelvin Lee, MD, has been named the new IU Simon Comprehensive Cancer Center director. In addition, Lee will hold the titles of senior associate dean of cancer research at IU School of Medicine and the H.H. Gregg Professor of Oncology. He will also direct the Cancer Institute, an umbrella entity designed to facilitate collaboration among cancer disciplines at IU School of Medicine and Indiana University Health, enhancing clinical research opportunities for patients here in Indiana and beyond. He will have appointments with both the Department of Medicine and the Department of Microbiology and Immunology.

Since 2006, Lee has served as the Jacobs Family Chair of Immunology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. The co-leader of the Cancer Center Tumor Immunology and Immunotherapy Program from 2006 to 2018, Lee led the group through three successful National Cancer Institute Cancer Center Support Grant renewals before stepping down to take on the position of Senior Vice President for the Basic Sciences.

The IU Simon Comprehensive Cancer Center has long been a leader in the field. It was recognized in 2019 as one of the top cancer research institutions in the nation when it was designated a Comprehensive Cancer Center by the National Cancer Institute. Home to the cure of testicular cancer, the IU Simon Comprehensive Cancer Center is a critical piece to IU School of Medicine’s world-class research enterprise. The central hub for cancer research across Indiana University, the center’s nearly 250 researchers conduct all phases of cancer research, from laboratory studies to clinical trials to population-based studies that address environmental and behavioral factors that contribute to cancer.

“Dr. Lee is the ideal leader to build on the IU Simon Comprehensive Cancer Center’s tremendous momentum. The center’s researchers are making great strides in improving health in current and future patients alike through their world-class care and groundbreaking research,” said 

, dean of IU School of Medicine and IU’s executive vice president for clinical affairs. “As an institutional leader, Dr. Lee will play a pivotal role in advancing these goals, and I’m excited for him to join our team at IU School of Medicine.”

As cancer center director, Lee will also play a key role in setting the future course for two significant centers at IU School of Medicine—the 

Vera Bradley Foundation Center for Breast Cancer Research

. The recruitment of a top-notch physician-scientist like Lee broadens the range of possibilities for the groundbreaking and potentially synergistic research taking place at both centers.

“We are very pleased to welcome one of the country’s top cancer physician-researchers to IU Health,” said 

, president and chief executive officer, Indiana University Health. “He joins an already respected program and will play a critical role in advancing our efforts, through the IU Simon Comprehensive Cancer Center and our new Cancer Institute, to expand access to cutting-edge cancer care to patients across and beyond Indiana.”

Lee assumes leadership at a time when the IU Simon Comprehensive Cancer Center will play a large role in a continued push by IU School of Medicine and IU Health leadership to improve alignment across education, research and clinical care. Earlier this year, the establishment of three institutes was announced, covering the key research areas of cardiovascular, neuroscience and cancer. Transcending multiple departments and centers, the goal of these institutes is to fully realize the promise of academic medicine and better address the most pressing challenges facing patients.

“I am very excited to join IU School of Medicine to continue to build the world-class effort in cancer research, education and care for the people of Indiana, nationally and globally. The renewal of the IU Simon Comprehensive Cancer Center core grant and achievement of comprehensive designation speaks to the outstanding faculty and staff that are leading this charge,” said Lee. “I have also been incredibly impressed by the deep commitment of IU School of Medicine and IU Health in these efforts, and this was a major reason in my decision to join IU.

“I believe that research cures cancer. For this to be successful, we need to get our science into our patients. The Cancer Institute and IU Simon Comprehensive Cancer Center are well-poised to grow this effort exponentially and will light the way to ending cancer’s darkness.”

As a physician-scientist, Lee’s research interests are both laboratory and clinical based. In the lab, his research efforts are RO1-funded and primarily focus on multiple myeloma, as well as myeloid dendritic cell differentiation in cancer. Lee currently sees patients with multiple myeloma once a week in clinic and is the principal investigator on active clinical trials of immunotherapy in myeloma at Roswell Park.

Lee officially assumes his new role in February 1, 2021. He succeeds 

, who served as cancer center director since 2009. Loehrer led the center through two National Cancer Institute competing renewals, which culminated with the center earning the prestigious Comprehensive Cancer Center designation. He will continue to see patients with gastrointestinal and thymic malignancies and carry on his work focused on global oncology and health equities.

Walther Cancer Foundation announces major gift

To help support the Cancer Institute, the Walther Cancer Foundation will contribute $15 million to establish a fund for investments in areas of cancer research and laboratory improvements that the director deems most promising.

The Walther Cancer Foundation IU Simon Comprehensive Cancer Center Director’s Fund is intended to provide the resources and flexibility needed to advance the work of a world-class cancer center, said Tom Grein, President and CEO of the Walther Cancer Foundation.

“It is not Walther’s position to decide, ‘This is where we want you to invest or that you need to use these funds in this explicit manner,’” Grein said. “It’s really more to give the director, who is recognized as a leader in cancer research, the ability to make those choices.”

The Walther Cancer Foundation will continue to fulfill previous commitments to IU cancer research through 2025, at which point its gifts to the Director’s Fund are scheduled to begin and continue for three years.

“This incredible gift from the Walther Cancer Foundation will be a tremendous asset in the years to come, offering the flexibility to add resources and attract talent to areas where there is a need,” Lee said.

Grein said the Walther Cancer Foundation was delighted by the cancer center’s comprehensive designation last year. And leaders at IU said it’s clear that the foundation’s support was a key ingredient in that success.

“The Walther Cancer Foundation’s generous support has been an essential element in the progress we’ve made in cancer research and in efforts to support the families of cancer patients,” Hess said. “We’re grateful for the confidence Walther has shown in us as we confront cancer in the lab, in the clinic and in our communities.”

 is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

Since its founding in 1985, the Walther Cancer Foundation has invested more than $165 million in cancer-focused medical research, and in research and education aimed at supporting cancer patients and their families. More than $100 million of that support has benefitted programs at the IU Simon Comprehensive Cancer Center. Those have included investments in the research of early career scientists, the field of bioinformatics and in supporting research and medical education aimed at helping cancer patients.

Indiana University School of Medicine has announced the hiring of a world-recognized medical oncologist and multiple myeloma researcher to lead the Indiana University Melvin and Bren Simon Comprehensive Cancer Center.

IU School of Medicine

Articles

IU Cancer Researchers Refining Colorectal Cancer Classification, Identifying New Targets for Treatment Using Cutting-Edge, Single-Cell Technology

IU School of Medicine names new cancer center director, announces $15 million supporting gift from Walther Cancer Foundation