Understanding the Role of CEACAM6 in Hard-to-treat Cancers

April is Bowel Cancer Awareness Month—an occasion to draw attention to the growing global burden of colorectal cancer, the screening methods that can potentially prevent cancer from developing, and the evolving treatment landscape for those already facing a diagnosis.

Colorectal cancer (CRC) has emerged as the second leading cause of cancer death worldwide, with CRC-related deaths expected to increase by 73% by 2040—to 1.6 million deaths per year.¹ What is especially worrying is that colorectal cancer is becoming increasingly common in younger adults. Known as early-onset CRC, since the mid-1990s, incidence rates in adults aged 20 to 39 years have consistently been increasing (by 2% each year), with one in five patients diagnosed today being under the age of 55.² Early-onset CRC is often diagnosed at a more advanced stage compared to patients with later-onset CRC (Stage III-IV), stealing away some of their most productive and creative years of life.³ Though no one knows for certain why there is an uptick in early-onset CRC, generational differences in diet, lifestyle factors (from sedentary lifestyles and obesity, to smoking and alcohol use), and environmental and genetic factors have all been associated with the disease.⁴

There are four early warning signs, each of which significantly increases the likelihood of being diagnosed with the early-onset form of CRC:⁵

Abdominal pain
Rectal bleeding
Diarrhea or changes in bowel patterns
Iron deficiency anemia

The belief that CRC typically affects older adults is still widespread, meaning younger adults are more likely to ignore early signs of the disease. This belief needs to change; younger adults experiencing these symptoms persistently should seek medical attention immediately.

If caught early, CRC is highly treatable and often curable if it is limited to the bowel. Approximately 50% of patients are cured with surgery alone.⁶ However, colon and rectal cancers can return within months or years of treatment—either locally in the bowel (locoregional recurrence) or as a metastasis somewhere else in the body (systemic recurrence), most commonly in the liver. Occurring in 4-12% of patients who have undergone curative resection surgery, locoregional recurrence is often more difficult to diagnose, while liver metastases can occur in up to 50% of patients after curative CRC treatment.⁷ Much of this ordeal be avoided with timely screening. Colonoscopy remains the gold standard of CRC screening and can, in fact, prevent precancerous polyps or lesions from becoming malignancies. Official guidelines recommend that both men and women of average risk should get colonoscopy screenings every 10 years starting at the age of 45.⁸

Recent breakthroughs have provided a glimmer of hope for those already facing a diagnosis, with innovative approaches including antibody-drug conjugates (ADCs), non-coding RNA-based strategies, and oncolytic viral therapies that have the potential to enhance treatment specificity and overcome drug resistance.⁹ Notably, in a recent Phase II study, the immune checkpoint inhibitor, Dostarlimab (JEMPERLI), achieved a remarkable complete remission in 100% of patients with specific types of rectal cancer.¹⁰ However, these successes are currently limited to select patient subgroups, and there is a lot of work ahead of us to address the global rise in colorectal cancer effectively. In this evolving landscape, targeting biomarkers like CEACAM6 offers a novel approach to broaden therapeutic impact and bridge current treatment gaps.

Understanding CEACAM6’s Biology and Overexpression

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is far more than a diagnostic marker – it is a potent driver of tumor aggressiveness.¹¹ This immunoglobulin superfamily protein is normally present on epithelial surfaces and certain immune cells, but in many aggressive cancers, its expression increases dramatically. Overexpression of CEACAM6 is closely linked to several key processes that fuel cancer progression:

Inhibition of Apoptosis: CEACAM6 helps cancer cells evade programmed cell death, allowing them to survive beyond their normal lifespan.
Promotion of Invasion and Metastasis: Elevated levels of CEACAM6 facilitate the breakdown of cell adhesion and extracellular matrix components, enabling cancer cells to migrate and form secondary tumors.
Enhancement of Drug Resistance: By activating survival pathways and modulating cell signaling, CEACAM6 contributes to a tumor’s ability to withstand conventional therapies.

High levels of CEACAM6 expression are correlated with poorer overall survival and disease-free survival in cancers such as lung, breast, colorectal, and pancreatic malignancies.¹² A detailed understanding of CEACAM6’s role not only underscores its value as a diagnostic marker but also positions it as a promising therapeutic target, paving the way for precise interventions using advanced technologies.

How We’re Targeting CEACAM6 with RDC and ADC Technology

Building on a robust scientific foundation, our approach at Helix BioPharma has evolved through extensive experience with CEACAM6-targeted treatments. Our work with L-DOS47, an antibody-enzyme conjugate that targets CEACAM6 and neutralizes the pH of the tumor microenvironment, has provided crucial insights into effective tumor targeting. We’ve used this experience to further the development of our next-generation oncology therapies.

Our lead discovery candidate is a radionuclide drug conjugate (RDC) targeting CEACAM6. RDCs represent an innovative strategy that uses precision targeting to deliver a radioactive payload directly to tumors. In RDCs, tumor antigen-specific antibodies or nanobodies are linked to radioisotopes, facilitating targeted radiotherapy by directing radiation precisely to the tumor site and minimizing exposure to healthy tissues.¹³ Recent studies in colon cancer have highlighted the need to improve the precision of targeting, addressing challenges such as the accumulation of nanoparticles in non-target tissues.¹⁴

Based on our clinical experience with L-DOS47, we now have the know-how to select nanobodies that minimize these risks. This precision targeting not only enhances the safety profile but also innovates from strength by delivering an established treatment modality, radiotherapy, with unprecedented accuracy. Research has consistently shown that CEACAM6 is overexpressed in colorectal tumors, where it drives progression and metastasis.¹⁵ This makes colorectal cancer a prime candidate for our CEACAM6-targeted RDC.

The Role of AI in Optimizing Targeting

Innovation at Helix BioPharma isn’t limited to conventional research but is also powered by cutting-edge artificial intelligence. We’re using AI to refine our antibody constructs, ensuring high binding affinity and optimal manufacturing yields. By analyzing the amino acid sequences that determine binding characteristics, our AI tools help us avoid problematic residues that cause aggregation, they help us streamline production, and enhance overall efficacy. This integration of AI-driven optimization not only accelerates our development timelines but also ensures that our CEACAM6-targeted therapies are as precise and effective as possible.

A New Paradigm in Precision Oncology

CEACAM6 is emerging as a central player in the battle against aggressive cancers, and at Helix BioPharma, we are at the forefront of transforming this knowledge into breakthrough treatments. By combining state-of-the-art RDC technology with AI-driven optimization, we are turning a once-overlooked biomarker into a powerful therapeutic target. This approach testifies to our commitment to innovating from strength, purposefully pushing the boundaries of proven science to deliver real-world impact for those who need it most. Together, we can turn the tables on cancer, paving the way for a future where even the most prevalent or aggressive cancers are rendered vincible.

But an even better outcome is to stop the cancer before it starts. It’s easy to put off, but if you’re eligible for a colonoscopy, penciling it in could be one of the most important appointments that you make.