By Ana Espino | Published on March 17, 2026 | 3 min readColorectal cancer (CRC) is the
third
most common cancer worldwide, with nearly
2 million new cases each year.
Despite the existence of screening programs, mortality remains high, with
5-year survival dropping from
91% at early stage to 15% at stage IV. At the
same time, the concerning rise in
early-onset cases (<50 years) is reshaping
the epidemiological landscape.
Current strategies rely on the fecal
immunochemical test (
FIT) and
colonoscopy, the diagnostic gold standard.
However, FIT has limited sensitivity for early lesions and advanced adenomas.
Colonoscopy, being invasive and costly, is difficult to implement at scale for
population-wide screening.
The current challenge is to identify
minimally invasive, cost-effective tools that are sensitive to early-stage
disease and capable of detecting not only tumor signals but also pre-malignant
metabolic and immune alterations. This review, published in Clinical and
Translational Medicine in 2025, examines the opportunities offered by
multi-omics molecular profiling to improve early CRC detection.
Can cancer be detected before it
develops?
The authors conducted a
comprehensive review of epidemiological data, molecular pathways involved in
tumorigenesis, and emerging diagnostic technologies.
Biologically, CRC develops through
the adenoma–carcinoma sequence, involving key mutations such as APC (≈80% of
cases), followed by alterations in KRAS, TP53, or SMAD4. Three major pathways
are described: chromosomal instability (70%), microsatellite instability (MSI),
and the CpG island methylator phenotype (CIMP). These alterations define four
consensus molecular subtypes (CMS1 to CMS4), highlighting tumor heterogeneity.
Regarding screening, FIT shows
variable sensitivity, which may drop to around 50% for stage I disease,
limiting its effectiveness for early detection. Recently approved blood-based
tests achieve sensitivities above 80% across all stages but remain less effective
for precancerous lesions.
Innovation lies in the integration
of
multi-omics liquid biopsies, combining genomics, proteomics, and
metabolomics. High-throughput proteomic platforms (Olink®, SomaScan®, Seer®)
enable the identification of plasma signatures associated with early-stage
disease. Some studies report areas under the curve (AUC) above
0.80 for CRC
detection.
Infrared spectroscopy represents an
original alternative. This technology analyzes the
global biochemical profile
of serum, integrating both tumor and non-tumor signals. A prospective study
reported
91% sensitivity for CRC, with
100% detection of stage I–II disease in
an exploratory cohort.
The article also emphasizes the
importance of
non-tumor information, including chronic inflammation, gut
dysbiosis, and metabolic reprogramming, which are present from premalignant
stages.
Toward integrated biological
screening
Colorectal cancer remains a major
public health issue, exacerbated by the rise in early-onset cases. The key
challenge is
detection before symptoms or advanced lesions appear.
This review aimed to assess the
potential of
integrated molecular profiling to transform screening. The data
suggest that multi-omics approaches—particularly those combining genomic,
proteomic, and metabolic signatures—could improve sensitivity for early-stage
disease.
Current limitations include cost,
large-scale clinical validation, and reproducibility in real-world settings.
Ultimately, integrating multi-omics
tools capable of simultaneously analyzing tumor-derived and microenvironmental
signals could enable personalized risk stratification, reduce unnecessary
colonoscopies, and support truly early detection of colorectal cancer.
Read next: CAR-T cells in colorectal cancer: the challenge of solid tumors
About the author – Ana Espino
PhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.
