Understanding Colorectal Cancer

Colorectal cancer is one of the most common and preventable cancers in the United States, yet it remains the second leading cause of cancer death when men and women are combined. In 2025 alone, an estimated 154,270 Americans were expected to be diagnosed with colorectal cancer, and approximately 52,900 were expected to die from the disease, according to the National Cancer Institute.

Colorectal cancer begins in the tissues of the large intestine, either in the colon (the main portion) or the rectum (the final 6 to 8 inches, along with the anal canal). While these are technically distinct cancer types, they share many biological features and are commonly discussed together.

Risk factors include family history, certain hereditary conditions, chronic inflammatory bowel diseases such as ulcerative colitis or Crohn's disease (lasting eight or more years), a personal history of colon or rectal polyps, smoking and heavy alcohol use (three or more drinks per day).

The Importance of Screening

Colonoscopy is one of the most effective tools in cancer prevention, not just detecting colorectal cancer early, but preventing it by identifying and removing precancerous polyps before they become malignant. Research has shown that colonoscopy can cut the risk of dying from colorectal cancer in half. Yet more than 30% of Americans are not up to date on colorectal cancer screening, according to the U.S. Centers for Disease Control and Prevention.

Current guidelines recommend that individuals at average risk begin colorectal cancer screening at age 45. Those with elevated risk factors, including family history or certain genetic conditions, may be advised to begin screening earlier. If unsure about your screening status, talk to your healthcare provider.

Colorectal Cancer in Our Region

The University of Cincinnati Cancer Center serves a catchment area of nearly 2.7 million people across seven counties in southwestern Ohio and three counties in northern Kentucky. This region is home to diverse communities, from densely populated urban neighborhoods to rural areas, each with distinct health profiles and access to care.

Within our region, colorectal cancer ranks as the 4th most common cancer type. Notably, both incidence and mortality rates in Ohio are slightly above the national average, and significantly higher in Kentucky. As the only academic cancer center serving this region, the Cancer Center is committed not just to treating colorectal cancer but to advancing the science behind it and improving outcomes for the patients and communities we serve.

Our Response: Research, Collaboration, and Clinical Expertise

Meaningful progress in colorectal cancer care emerges at the intersection of research, clinical practice, and cross-disciplinary collaboration, an approach central to the Cancer Center's work. On March 6, 2026, the Cancer Center hosted its 4th Biennial GI Symposium, bringing together clinicians and researchers for a full-day program on the multidisciplinary management of colorectal cancer. Held at UC's Digital Futures Building, the symposium featured presentations and panel discussions spanning clinical trials, molecular targeting strategies, survivorship care and advances in anal cancer treatment.

The program opened with welcome remarks from Carla F. Justiniano, MD, MPH, Co-Director of the Young Onset Colorectal Cancer Program, and Davendra Sohal, MD, MPH, Associate Director of Clinical Research at the Cancer Center. Sessions covered a broad range of topics central to colorectal cancer care, including clinical trial updates led by Dr. Sohal, combined KRAS and HER family targeting presented by Joan Garrett, PhD, and a case-based discussion of young onset colorectal cancer led by Ian Paquette, MD, reflecting the growing national focus on rising incidence in patients under 50. Survivorship care and the risk of subsequent colorectal cancers were addressed by Melissa G. Erickson, MD, Director of Cancer Survivorship and Supportive Services at UC Health, an increasingly important dimension of care as treatment outcomes improve. The afternoon session turned to anal cancer, covering screening updates, emerging approaches to treatment de-escalation and the role of circulating tumor DNA, led by Earl V. Thompson IV, MD, Bailey A. Nelson, MD, and Jordan R. Kharofa, MD, who also moderated a case-based discussion on anal cancer management.

Research Spotlight: Targeting Resistance in Colorectal Cancer

One of the most important and persistent challenges in colorectal cancer treatment is drug resistance. Roughly 41% of colorectal cancers harbor a mutation in the KRAS gene, a driver mutation that has long been considered difficult to target. While KRAS inhibitors have emerged as a promising class of drugs, cancer cells have a well-documented ability to develop resistance to single-agent therapies over time.

New research led by University of Cincinnati investigators is tackling this challenge head-on. A recently published study, "Co-targeting KRAS^G12D and the HER family is efficacious in colorectal cancer," led by Joan Garrett, PhD, a member of the Cancer Center’s Experimental Therapeutics Research Program, explores a novel combination strategy that may help overcome this resistance.

Joan Garrett, PhD Member, Experimental Therapeutics Research Program University of Cincinnati Cancer Center

The research centers on the most common KRAS mutation in colorectal cancer, KRAS^G12D mutation and its relationship with the HER family of proteins, particularly HER3. When KRAS-targeted treatments are used, the study found that HER3 levels increase in colorectal cancer cells and patient-derived organoids (lab-grown tumor models), suggesting the cancer is adapting and using HER3 as an escape route.

Dr. Garrett's team found that simultaneously targeting both KRAS^G12D and HER3, either genetically or through drug combinations, produced synergistic effects in reducing cancer cell growth. Combining a KRAS^G12D inhibitor (MRTX1133) with pan-HER inhibitors, or pairing the inhibitor with a HER3 antibody-drug conjugate, further diminished cell viability compared to either approach alone.

This work, supported by an active grant running through 2027, underscores the Cancer Center's commitment to precision oncology, designing therapies that anticipate and address the ways cancer evolves in response to treatment. It also highlights the power of UC-led research to move the needle on one of the most lethal and molecularly complex cancers we face.