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Updated: Aug 6, 2026
09:29
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Next-generation precision oncology in microsatellite stable colorectal cancer: integrated targeting beyond RAS and
M Bartolini1, S Algaze2, H-J Lenz2
1Division of Medical Oncology, Department of Gastrointestinal Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA; Department of Biomedical Sciences, Humanitas University, Milan, Italy.
ESMO Open
|July 16, 2026
Summary
Colorectal cancer (CRC) treatment advances include targeted therapies for molecular subtypes. New strategies like antibody-drug conjugates and TME modulation aim to overcome resistance in microsatellite-stable tumors.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Colorectal cancer (CRC) treatment has advanced with molecular subtyping, enabling precision therapies for specific populations.
- However, microsatellite-stable (MSS) CRC remains challenging due to tumor heterogeneity, resistance, and an immunosuppressive tumor microenvironment (TME).
Purpose of the Study:
- To review novel therapeutic strategies for colorectal cancer, focusing on overcoming resistance mechanisms in MSS tumors.
- To highlight emerging targets and approaches, including antibody-drug conjugates, bispecific antibodies, and TME-directed therapies.
Main Methods:
- Review of recent advances in molecular profiling, spatial biology, and immune characterization in CRC.
- Analysis of emerging therapeutic modalities targeting novel vulnerabilities and the TME.
- Examination of biomarker-driven approaches and artificial intelligence in personalized CRC treatment.
Main Results:
- HER2-directed antibody-drug conjugates (ADCs) show promise in HER2-positive metastatic CRC.
- Bispecific antibodies and novel immune checkpoint inhibitors are being developed to address antigen heterogeneity and T-cell dysfunction.
- Emerging strategies focus on TME modulation, DNA damage response (DDR) targeting, and epigenetic therapies to enhance treatment efficacy.
Conclusions:
- Novel therapeutic strategies, including ADCs, bispecific antibodies, and TME modulation, offer new hope for colorectal cancer patients, particularly those with MSS tumors.
- Integrated biomarker approaches and AI are crucial for guiding personalized therapy and overcoming resistance.
- Continued research into novel targets and combination therapies is essential to broaden the benefit of precision medicine in CRC.
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