Reading time: 5 minutes
Xanthea Heighington
Colorectal cancer is the third most prevalent cancer in the world. Despite significant advancements in screening and treatment, it remains the cause of 9.2% of all cancer related deaths [1]. In the next 10 years, estimates have shown that cases of colon cancer could rise by about 71.5%, and cases of rectal cancer could increase by around 60% [2]. Therefore, the development of new therapies for colorectal cancer is a pressing and ongoing need.
Colorectal organoids are tiny, 3D ‘mini-tumours’ grown in a lab from real patient tumour cells. They closely represent the structure, genetics and behaviour of tumours within the body. This makes them a powerful tool for exploring new treatment strategies. There are many ways that researchers try to tackle colorectal cancer, from chemotherapy to targeted vaccines and personalised immunotherapy, to the use of bacterial products and even herbal medicines. Because organoids reflect how cancers actually respond in the human body, they have recently been used as a reliable and versatile platform for developing and refining effective colorectal cancer therapies.
Cancer vaccines
In an immune-colorectal tumour organoid model, researchers tested a vaccine designed to stop MICA/B, a commonly-expressed stress protein in tumours, from shedding an immunorepressive piece of itself. This particular region downregulates NKG2D, a key activator of immune cells, resulting in reduced immune cell activity. By preserving this part of the protein that is usually shed on the surface of tumour organoids, the vaccine made the organoids significantly more vulnerable to killing when exposed to patient-derived immune cells [3].
Chinese Traditional Medicine
Recently tested in colorectal cancer organoid models was SQYC, a Chinese herbal medicine comprising six key components, in conjunction with sintilimab, a drug known to enhance the immune system’s ability to recognise and destroy cancer cells. It does this by blocking PD-1, a molecular switch which is “off” in normal cells, preventing immune destruction. Cancer cells exploit this switch to evade detection by the immune system. Following 7 days of combination treatment with SQYC and sintilimab, the volume of the organoids was significantly reduced compared to those treated with the sintilimab alone. Findings indicated that the Chinese herbal medicine increased the efficacy of the cancer drug, rather than having its own anti-tumour effects [4].
Microbial therapeutics
Exopolysaccharides (EPSs) are complex sugars produced by bacteria and secreted into their environment in the form of either loosely bound slime or a tightly bound capsule. Several EPSs produced by bacteria are known to have anti-inflammatory properties. Bifidobacterium are a common type of bacteria found naturally in the gut. EPSs from two strains of Bifidobacteria were added to colon cancer organoids and were found to enhance anti-tumor immunity in these models. They were found to drive this process through signalling proteins (also known as cytokines) used by T cells, a specific type of immune cell that identify and destroy cancer cells [5].
CAR-T cell therapy
CAR-T cells are genetically engineered immune cells specifically designed to target and destroy cancer cells. B7-H3 is a protein attached to the membrane of cancer cells, which helps them to evade the immune system by downregulating T cell activation. This contributes to tumour growth, spread and resistance to treatment. In a recent study by Sheng et al., T cells with a specific receptor added to identify the B7-H3 protein, which they would usually overlook, were added to colorectal cancer organoids. Researchers found that these modified T cells caused a significant reduction in viable cancer cells, changes to their shape and disruption of membrane integrity [6].
Chemotherapy
Trifluridine-tipiracil (Lonsurf) is a combination medication sometimes used to treat colorectal cancer. Trifluridine disrupts the DNA in cancer cells, while the tipiracil component inhibits the breakdown of the drug by the body, enhancing its effectiveness. Organoids have recently been used to better understand the mechanisms underlying the anticancer effects of this drug, which are poorly understood. Researchers found that Lonsurf activates a specific type of cell death called ferroptosis. It does this by stabilising p53, a protein that inhibits the expression of SLC7A11, a transporter protein that is essential for the neutralisation of unstable molecules in cells. Additionally, the researchers observed that in organoids treated with Lonsurf and sulfasalazine, an anti-inflammatory drug, the growth of colorectal cancer cells was further inhibited [7].
Key Takeaways
Research published in 2025 has shown that organoids are invaluable in increasing understanding of potential treatment mechanisms for colorectal cancer in the following ways;
- Testing how vaccines can restore immune recognition of tumours, helping to show that blocking MICA/B shedding boosts immune cell activity.
- Safely assessing combination treatments, revealing that the herbal formula SQYC enhances the effects of the immunotherapy drug sintilimab.
- Linking gut microbes to tumour control, demonstrating that bacterial exopolysaccharides trigger immune-driven cancer cell death.
- Refining targeted immunotherapies, confirming the ability of modified T cells to recognise and destroy B7-H3-positive cancer cells
- Deepening our understanding of how existing drugs work, uncovering that Lonsurf induces ferroptosis through p53 stabilisation.
These studies all show that across diverse research areas, colorectal cancer organoids provide realistic and reliable models for evaluating how different therapies act on tumour cells. While findings from organoids are still early-stage, and don’t guarantee success in human patients, their ability to capture the complexity of real cancers makes them powerful tools for discovering and improving potential treatments for the future.
Header Image Source: Photo by Louis Reed on Unsplash
Edited by Ian Padykula
References
- Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12. Erratum in: CA Cancer J Clin. 2021 Jul;71(4):359. doi: 10.3322/caac.21669
- Sawicki T, Ruszkowska M, Danielewicz A, Niedźwiedzka E, Arłukowicz T, Przybyłowicz KE. A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers (Basel). 2021 Apr 22;13(9):2025. doi: 10.3390/cancers13092025
- Wang R, Wu J, Lin Y, et al. An epitope-directed mRNA vaccine inhibits tumor metastasis through the blockade of MICA/B α1/2 shedding. Cell Rep Med. 2025;6(3):101981. doi:10.1016/j.xcrm.2025.101981
- Wang H, Ji Y, Deng S, Qin XY, Ye XT, Sun YY, Che XY, Yang L, Huang CY, Chen Y, Liu YP. SQYC formula improves the efficacy of PD-1 monoclonal antibodies in MSS colorectal cancer by regulating dendritic cell mitophagy via the PINK1-Parkin pathway. Phytomedicine. 2025 Mar;138:156388. doi: 10.1016/j.phymed.2025.156388
- Silva de Oliveira R, Shupe A, Krause T, Richardo T, Ohland C, Sabachvili M, Bucher K, Hetzer J, Hörner S, Dauch D, Heikenwälder M, Trautwein C, Weber ANR, Klepsch V, McCoy KD, Mager LF. Bifidobacteria-derived exopolysaccharide promotes anti-tumor immunity. Cell Rep. 2025 Sep 23;44(9):116223. doi: 10.1016/j.celrep.2025.116223
- Sheng Y, Yan L, Liu Q, Peng Y, Tan J, Li W, Mao W, Wei W, Chang Y, Cao L, Tan Y, Xiao Y, Zhang W, Gao J, Xu Y, Du C. The pronounced cytotoxic effects of chimeric antigen receptor T cells targeting B7-H3 in organoids and liver xenografts derived from colorectal cancer patients. Br J Cancer. 2025 Oct;133(7):1056-1065. doi: 10.1038/s41416-025-03114-1
- Huang M, Wu Y, Wei X, Cheng L, Fu L, Yan H, Wei W, Li B, Ru H, Mo X, Tang W, Su Z, Yan L. Trifluridine/tipiracil induces ferroptosis by targeting p53 via the p53-SLC7A11 axis in colorectal cancer 3D organoids. Cell Death Dis. 2025 Apr 5;16(1):255. doi: 10.1038/s41419-025-07541-z
OncoBites 
Leave a comment