INDIANAPOLIS — 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.
Their work, led by Ashiq Masood, MD, associate professor of medicine at IU School of Medicine, was recently published in Genome Biology. 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 Ateeq Khaliq, PhD, Yong Zang, PhD, and Yingjie Qiu; and IU Simon Comprehensive Cancer Center members Yunlong Liu, PhD, Melissa L. Fishel, PhD, and Anita Turk, MD.
IU School of Medicine is the largest medical school in the United States 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.
INDIANAPOLIS — Indiana University School of Medicine has named Shelley Johns, PsyD, ABPP, the Walther Scholar in Psycho-Oncology.
Johns is the first person to hold this position, which was established by the transformative $14 million gift to IU School of Medicine from the Walther Cancer Foundation to create five endowed positions to develop a supportive oncology program that encompasses research and patient care. Supportive oncology goes beyond standard therapies such as surgery, chemotherapy and radiation and seeks to care for a patient’s overall physical, mental and spiritual well-being.
The program intends to influence care for cancer patients and their families throughout Indiana and the country by providing expertise and best practices for other health systems to model, with particular attention to the underserved.
“Thanks to the generous support of the Walther Cancer Foundation, I have the opportunity to explore new ideas to address problems that are most important to people whose lives are disrupted by cancer,” Johns said. “I want to capitalize on the synergy that I already see and feel between clinical practice and research so we can develop studies that are informed by people with cancer and then implement our research findings in clinical practice.”
Johns is a nationally-recognized, board-certified, clinical health psychologist, an associate professor at IU School of Medicine in the Division of General Internal Medicine and Geriatrics, an IU Simon Comprehensive Cancer Center researcher and a research scientist at the William M. Tierney Center for Health Services Research at the Regenstrief Institute. Her research focuses on developing and testing mind-body interventions to improve the physical health and psychological well-being of adults with cancer. She currently holds a $2.6 million grant from the National Cancer Institute to lead a clinical trial to support breast cancer survivors struggling with fear of cancer recurrence.
As the Walther Scholar in Psycho-Oncology, Johns will develop programs in psycho-oncology within the newly established Supportive Oncology Center of Excellence at the IU Simon Comprehensive Cancer Center.
“We are very fortunate to recruit Dr. Johns to the newly established Supportive Oncology Center of Excellence in the cancer center, which will be the hub for our cutting-edge efforts in research, education and clinical care in supporting the important needs of our cancer patients and their families,” Kelvin Lee, MD, cancer center director, said. “Dr. Johns’ exceptional work in psycho-oncology will be a major pillar of the center.”
“Dr. Johns is a great addition to improving the total care of patients living with cancer who we see at the cancer center. Shelley’s work will be critical to the Supportive Oncology Center of Excellence in improving clinical care, research and education,” James Cleary, MD, professor of medicine and Walther Senior Chair in Supportive Oncology at IU School of Medicine, said. Cleary was recruited in 2018 to IU as part of the Walther gift, which was believed to be the largest gift in the country to support a program of this kind.
“Dr. Johns does very rigorous and sophisticated research aimed at providing the evidence base for treating highly prevalent and challenging symptoms in patients with cancer,” said Greg Sachs, MD, director of the Division of General Internal Medicine and Geriatrics. “She also represents another critical connection between our palliative care program and the cancer center.”
“Shelley Johns is a highly talented and insightful researcher. The Walther Cancer Foundation has provided support for certain aspects of Dr. John’s work for more than ten years. We are truly pleased that Shelley has been selected as the first Walther Scholar in Psycho-Oncology,” said Tom Grein, president and CEO of the Walther Cancer Foundation.
IU School of Medicine 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.
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