More recently, healthcare professionals have been increasingly concerned about a troubling trend: colorectal cancer is affecting younger people at an alarming rate. While overall colorectal cancer rates have been declining in older adults thanks to increased screening, the incidence in people under 50 has been rising by approximately 2.4% per year from 2012 to 2021.

If current trends continue, colorectal cancer is projected to become the leading cause of cancer, related deaths among young adults by 2030.

What makes this particularly perplexing is that many young adults diagnosed with colorectal cancer have no family history of the disease or other known risk factors.

A Breakthrough Discovery: The Colibactin Connection

A groundbreaking study published in Nature in April 2025 may have uncovered a crucial piece of this puzzle. Researchers analyzed 981 colorectal cancer genomes from patients across 11 countries and made a remarkable discovery that could explain why we’re seeing more colorectal cancer in younger people.

What Is Colibactin?

Colibactin is a toxin produced by certain strains of Escherichia coli (E. coli) bacteria that can reside in our colon and rectum. While E. coli is commonly found in the human gut,  only specific strains produce this potentially dangerous toxin.

The Study’s Key Findings

The research revealed several critical insights:

1. Early childhood exposure: The colibactin toxin can leave a distinct genetic signature in colon cell DNA,  particularly when exposure occurs during early childhood.

    

2. Significantly higher prevalence in early, onset cases: These specific DNA mutation patterns were 3.3 times more common in patients diagnosed with colorectal cancer before age 40 compared to those diagnosed after age 70.

    

3. Geographic correlation: These patterns were more prevalent in countries with higher incidences of early, onset colorectal cancer cases.

    

4. Timing of mutations: By molecularly dating these mutational signatures, researchers estimated that colibactin associated mutations occurred within the first 10 years of life, decades before cancer might develop.

    

5. Contribution to cancer development: The study estimated that colibactin related mutations might account for approximately 15% of APC driver mutations,  which are early genetic changes that promote cancer development.

    

The Proposed Model

Researchers proposed a concerning model: colibactin, producing bacteria, might silently colonize children’s colons,  initiating DNA damage that could eventually lead to colorectal cancer many years later. It’s like planting seeds of potential cancer that take decades to grow.

While these findings strongly suggest a link between childhood colibactin exposure and early onset colorectal cancer, researchers emphasize that further studies are needed to establish a definitive cause, and, effect relationship.

Future Research Directions

Scientists are now focusing on:

• Understanding how children are exposed to colibactin, producing bacteria
• Identifying environments and behaviors that might foster these bacteria
• Developing tests to detect these specific DNA mutations
• Exploring ways to mitigate exposure to this bacterial toxin

Treatment Breakthroughs

For those facing advanced colorectal cancer,  recent treatment advances provide compelling reasons for optimism. The landscape of colorectal cancer treatment is evolving rapidly,  with several groundbreaking approaches showing remarkable promise.

Immunotherapy Milestone

In April 2025, the U.S. Food and Drug Administration (FDA) approved the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) as a first line treatment for metastatic colorectal cancer with specific genetic markers.

This approval specifically targets adult and pediatric patients (12 years and older) whose cancers show microsatellite instability, high (MSI, H) or mismatch repair deficient (dMMR) characteristics, genetic features found in approximately 5% of metastatic colorectal cancers.

The approval was based on updated findings from the CheckMate, 8HW clinical trial,  which demonstrated impressive results:

• After three years of treatment,  approximately 68% of patients receiving the combination therapy were still alive without disease progression
• In comparison,  only 51% of patients treated with nivolumab alone achieved the same outcome
• This represents a substantial 17 percentage point improvement in progression, free survival

Note: the combination did come with more side effects, 22% of patients experienced serious side effects compared to 14% with nivolumab alone, and more patients discontinued treatment due to side effects (14% versus 6%). 

Personalized Immune Cell Therapy

Another exciting development comes from a clinical trial led by researchers at the National Institutes of Health (NIH),  which reported promising results for a new form of tumor infiltrating lymphocyte (TIL) therapy in patients with metastatic gastrointestinal cancers,  including colon and rectal cancers.

This highly personalized approach to cancer immunotherapy involves:

1. Selection: Identifying immune cells from the patient’s own tumor that specifically recognize and attack cancer cells
2. Expansion: Growing these specialized immune cells in the laboratory
3. Reinfusion: Administering the expanded cells back to the patient

The trial included 91 patients with various metastatic gastrointestinal cancers whose conditions had worsened despite prior treatments. In the third phase of the trial:

• Patients received the immune checkpoint inhibitor pembrolizumab immediately before the selected TIL therapy
• This combination prevented inactivation of the introduced immune cells
• Nearly 24% of patients experienced a substantial reduction in tumor size
• This compared favorably to just 7.7% of patients who received selected TILs without pembrolizumab

Targeted Treatments For Specific Mutations

The field of colorectal cancer treatment is increasingly moving toward precision medicine, treatments tailored to the specific genetic characteristics of each patient’s cancer. 

Fast Track Designation for Invikafusp Alfa

Marengo Therapeutics’ dual T, cell agonist invikafusp alfa (STAR0602) received FDA fast track designation in April 2025 for the treatment of high tumor mutational burden (TMB, H) colorectal cancer. This designation,  based on promising data from the START, 001 trial showing enhanced antitumor activity,  is designed to expedite the development and review of the drug.

Fast track designation is granted to treatments that address serious conditions and fill an unmet medical need, suggesting the significant potential of invikafusp alfa as a future treatment option for this specific subgroup of colorectal cancer patients.

The Takeaway

The discovery of colibactin’s potential role in early, onset colorectal cancer,  coupled with the approval of new treatments and promising clinical trial results,  highlights the dynamic and rapidly evolving nature of colorectal cancer research and treatment.

For young adults,  these findings emphasize the importance of awareness and early detection.

For those already diagnosed with colorectal cancer,  these advances represent an expanding toolkit of treatment options that may offer better outcomes and quality of life.

As research continues to advance our understanding of this disease and its treatment,  there’s increasing hope that we can turn the tide against colorectal cancer, both for young adults facing early onset disease and for all patients across the spectrum of this challenging condition.

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Disclaimer

Before making any decisions regarding anesthesia, sedation options, colonoscopies, or any medical procedure, always consult with your physician, anesthesiologist, or qualified healthcare provider. This article should not be used as a substitute for professional medical advice, diagnosis, or treatment.