Advancing breakthrough research and treatments for the disease, the national cancer research and treatment organization is developing a blood test that could change screening practices

Experts at City of Hope, one of the nation’s largest and most advanced cancer research and treatment organizations, say the surge in colorectal cancer in people under 50 — often compounded by delayed diagnoses and misinterpreted symptoms — requires age-specific research, treatments, education, and diagnostic tools. A blood test under development at City of Hope could become a breakthrough for detecting the disease early, making it part of an annual exam.

Colorectal cancer — now the leading cause of cancer deaths in people younger than 50 — is largely preventable and highly treatable if detected early. Almost all colorectal cancers begin as precancerous polyps, which can be removed during colonoscopy. Yet, with current “gold standard” colonoscopy screening guidelines beginning at age 45, more definitive, age-adapted screening tools are urgently needed.

Among the most promising is a blood test developed by Ajay Goel, Ph.D., professor and chair, Department of Molecular Diagnostics and Experimental Therapeutics at City of Hope. The first viable tool for detecting disease in people without symptoms, this single, inexpensive test in development could change screening practices. Goel foresees people as young as 18 being tested during an annual exam, long before symptoms appear.

“If you detect colorectal cancer early — at Stage 1 or at the advanced polyp stage — it is nearly 100 percent curable,” Goel says. “This test, when it becomes available, could be a game-changing public health breakthrough.”

Prevention, Early Diagnosis and Treatment Are Critical

Across the country, rates of colorectal cancer in people under 50 increased 2.9 percent each year from 2013 to 2022. In line with the national trend, physicians across City of Hope’s national system are seeing a rise in patients under 50 with colorectal cancer. According to a new report released by the American Cancer Society, people born in 1990 are twice as likely as those born in 1950 to develop colon cancer, and four times as likely to develop rectal cancer.

“It’s clear from the data everywhere that this is on the rise. While there's still uncertainty as to what the main driver is — physical activity, microbiome, microplastics, ultra-processed food, alcohol intake at a young age, amongst others — our focus for now is on prevention, early diagnosis and treatment,” said Marwan G. Fakih, M.D., deputy director of City of Hope Comprehensive Cancer Center, division chief of gastrointestinal medical oncology and a renowned researcher and clinician pioneering treatments for advanced colorectal cancer.

Many of these younger patients face delayed diagnoses because symptoms are often misattributed to hemorrhoids or pregnancy-related changes.

“Every young patient I’ve ever diagnosed with colon or rectal cancer was told they had hemorrhoids,” said Lance Uradomo, M.D., an interventional gastroenterologist at City of Hope. In fact, three-fourths of patients are diagnosed with advanced disease.

A Different, More Aggressive Cancer

About 65 percent of colorectal cancer cases in people younger than age 50 occur on the left side of the colon or in the rectum. Experts believe these tumors develop and progress much faster in younger patients than in older patients.

“These appear to be biologically different tumors. Yet, even in Stage 4 colorectal cancer, cure is still on the table with the right multidisciplinary approach and next-generation immunotherapies,” said Pashtoon Kasi, M.D., medical director of gastrointestinal medical oncology at City of Hope Orange County.

Some scientists believe there may be a link between microbiome changes.

“We are examining how diet, antibiotic exposure and environmental disruptions to gut bacteria may influence cancer risk and treatment response. These investigations are leading us to understand that nutrition isn’t just fuel. It’s an immune modulator. We are adding more microbiome strategies to join the cancer care toolkit,” said Marcel van den Brink, M.D., Ph.D., president, City of Hope Los Angeles and City of Hope National Medical Center and a noted researcher on the microbiome’s impact on cancer.

Treatment Advances Offering New Hope

City of Hope researchers and clinicians are advancing important research in the field and pioneering new treatment approaches targeting the biology of colorectal cancer, with promising results.

• A major effort focuses on balancing treatment efficacy and toxicity. A new Phase 2 study is testing a combination of standard chemotherapy with two immunotherapies that help the immune system spot and attack cancer cells. The trial is the first to test this specific combination of novel immune checkpoint inhibitors in people just diagnosed with early-stage rectal cancer. This could allow patients — especially younger adults — to preserve fertility, sexual function and long-term bowel and bladder health.

• A new study shows encouraging early results for a drug called ADG126, used together with pembrolizumab (Keytruda), in treating microsatellite-stable (MSS) colorectal cancer, which usually does not respond to immunotherapy. In the study, about 29 percent of patients saw their tumors shrink and many also experienced fewer side effects. This regimen is now progressing into a randomized Phase 1 trial and holds potential to redefine treatment for this kind of colorectal cancer.

• City of Hope researchers have identified biomarkers of immune response, which help predict which patients will most likely benefit from immunotherapy. This discovery supports more personalized and precise treatment plans for patients with colorectal cancer.

• City of Hope led the first Phase 3 trial to show a clear benefit for patients with the hard-to-treat KRAS G12C mutation. The combination of sotorasib and panitumumab improved outcomes compared to standard chemotherapy, leading to Food and Drug Administration approval of a new treatment option for this patient population.

• The National Cancer Institute is funding a five-year, $18.5 million Cancer Moonshot project led by John D. Carpten, Ph.D., City of Hope’s Chief Scientific Officer, and David W. Craig, Ph.D., Chair, Department of Integrative Translational Sciences, to better understand colorectal cancer in Hispanic and Latino communities. In collaboration with researchers from the University of Southern California, the team is improving ways to engage Hispanic and Latino patients in genomic research so scientists can better study the genes and tumor characteristics involved in the disease. This work also connects to broader Cancer Moonshot research that examines early-onset colorectal cancer in Hispanic and Latino patients — the population with the highest rate of increase in early onset disease — to uncover important genetic patterns that could lead to better diagnostics and treatments in the future.

City of Hope’s colorectal cancer program is also distinguished by its exceptional surgical expertise, particularly in performing complex synchronous colectomy and liver resections for patients with metastatic disease. City of Hope has received national recognition as a high-performing hospital for colon cancer surgery. Experts have deep understanding and extensive experience using the latest technologies, including minimally invasive approaches that provide patients with shorter recovery times.

Supportive Care Is Key

For all cancers, supportive care to help long-term survivors is critical. Younger people, living for decades post-diagnosis, need support navigating the physical, financial, social and emotional aspects of many years of life after cancer.

“Our younger patients are in the building stages of life, planning or beginning families and careers, so this is a particularly challenging time to receive a cancer diagnosis. Our responsibility extends far beyond treatment alone. We offer critical support and assist with emotional, physical and practical challenges, strengthen couples to optimally face this crisis, offer fertility preservation guidance, survivorship care, and resources to reclaim their lives after cancer,” said Andrew T. Leitner, M.D., chair, Department of Supportive Care Medicine. “Our goal is not only to treat the cancer but also to help patients maintain the quality of life, ambitions and futures they’re working hard to build.”

What to Look Out For:

• Pay attention to persistent changes in bowel habits, bleeding, fatigue, weight loss or other symptoms. Don’t be embarrassed. Tell your doctor.

• Ask your doctor when to start screening and which test is right for you — even if you are under 45.

• Learn more about City of Hope’s research in colorectal cancer and meet the younger faces of this disease.

About City of Hope

City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the United States, and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked among the nation’s top cancer centers by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, Orange County, California, campus, a network of clinical care locations across Southern California and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHope™. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.

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