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Updated: Aug 5, 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
Targeting Tex10 Overcomes Oxaliplatin Resistance by Competitively Disrupting the Non-Canonical BAF Complex in
Ping Xu1,2, Jie Huang1,2, Xiaojin Gao1,2,3
1Institute of Hepatobiliary-Pancreatic-Intestinal Diseases, Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 29, 2026
Summary
Tex10 deficiency enhances oxaliplatin (OXA) sensitivity in colorectal cancer (CRC) by inducing autophagy. Gemcitabine (GEM) inhibits Tex10, boosting autophagy and overcoming OXA resistance, while also improving immunotherapy outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Oxaliplatin (OXA)-based chemotherapy is first-line for colorectal cancer (CRC), but resistance is a major challenge.
- Understanding the molecular mechanisms of OXA resistance is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the role of Tex10 in OXA resistance in CRC.
- To identify potential therapeutic strategies to overcome OXA resistance and enhance immunotherapy.
Main Methods:
- Utilized xenograft and patient-derived organoid models to assess Tex10's impact on OXA sensitivity.
- Investigated the molecular mechanism involving Tex10, BRD9, BRG1, AMBRA1, and ULK1.
- Performed in silico screening to identify Tex10 inhibitors, leading to gemcitabine (GEM) discovery.
Main Results:
- Tex10 deficiency significantly enhanced OXA sensitivity by inducing cytostatic autophagy.
- Tex10 deletion reduced tumor burden in mice and suppressed key autophagy regulators.
- Gemcitabine (GEM) was identified as a Tex10 inhibitor that triggers a positive feedback loop to overcome OXA resistance.
- Tex10 deletion enhanced immunotherapy efficacy by preventing PD-L1 lysosomal degradation.
Conclusions:
- Tex10 is a critical regulator of OXA resistance in CRC.
- Gemcitabine (GEM) offers a novel therapeutic approach by targeting Tex10 to overcome OXA resistance and potentiate immunotherapy.
- Tex10 represents a promising therapeutic target for CRC treatment.
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