ArticleScientific reports2017
Rationally co-targeting divergent pathways in KRAS wild-type colorectal cancers by CANscript technology reveals tumor dependence on Notch and Erbb2.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Advancements in 3D In Vitro Models for Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells.British journal of cancer · 2024Article
- Mismatch repair-proficient tumor footprints in the sands of immune desert: mechanistic constraints and precision platforms.Frontiers in immunology · 2024Review
- Use of patient-derived explants as a preclinical model for precision medicine in colorectal cancer: A scoping review.Langenbeck's archives of surgery · 2023Article
- NovelFrontiers in oncology · 2022Review
- Review
- JAK-STAT inhibitor as a potential therapeutic opportunity in AML patients resistant to cytarabine and epigenetic therapy.Cancer biology & therapy · 2021Article
- Patient-Derived Explants as a Precision Medicine Patient-Proximal Testing Platform Informing Cancer Management.Frontiers in oncology · 2021Review
- Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2020Article
- Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival.Nature communications · 2020Article
- Article
- Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery.British journal of cancer · 2020Review
- Frequent Activation of Notch Signaling Pathway in Colorectal Cancers and Its Implication in Patient Survival Outcome.Journal of oncology · 2020Article
- Regulation of the unfolded protein response through ATF4 and FAM129A in prostate cancer.Oncogene · 2019Article
- Activation of Epithelial-Mesenchymal Transition and Altered β-Catenin Signaling in a Novel Indian Colorectal Carcinoma Cell Line.Frontiers in oncology · 2019Article
- Ex-vivo organ culture as potential prioritization tool for breast cancer targeted therapy.Cancer biology & therapy · 2018Article
- Prediction of Target Genes and Pathways Associated With Cetuximab Insensitivity in Colorectal Cancer.Technology in cancer research & treatment · 2018Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KRAS mutation status can distinguish between metastatic colorectal carcinoma (mCRC) patients who may benefit from therapies that target the epidermal growth factor receptor (EGFR), such as cetuximab. However, patients whose tumors harbor mutant KRAS (codons 12/13, 61 and 146) are often excluded from EGFR-targeted regimens, while other patients with wild type KRAS will sometimes respond favorably to these same drugs. These conflicting observations suggest that a more robust approach to individualize therapy may enable greater frequency of positive clinical outcome for mCRC patients. Here, we utilized alive tumor tissues in ex-vivo platform termed CANscript, which preserves the native tumor heterogeneity, in order to interrogate the antitumor effects of EGFR-targeted drugs in mCRC (n = 40). We demonstrated that, irrespective of KRAS status, cetuximab did not induce an antitumor response in a majority of patient tumors. In the subset of non-responsive tumors, data showed that expression levels of EGFR ligands contributed to a mechanism of resistance. Transcriptomic and phosphoproteomic profiling revealed deregulation of multiple pathways, significantly the Notch and Erbb2. Targeting these nodes concurrently resulted in antitumor efficacy in a majority of cetuximab-resistant tumors. These findings highlight the importance of integrating molecular profile and functional testing tools for optimization of alternate strategies in resistant population.
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