ArticleGastroenterology2021
Sequential Administration of XPO1 and ATR Inhibitors Enhances Therapeutic Response in TP53-mutated Colorectal Cancer.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Targeting p53 in Cancer: Functional States, Therapeutic Strategies, and Clinical Progress.Cancers · 2026Review
- NSMF modulates replication stress to facilitate colorectal cancer progression.Nucleic acids research · 2026Article
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Exportin 1 inhibitor KPT‑330 reverses oxaliplatin resistance via p53 nuclear retention in colorectal cancer.International journal of molecular medicine · 2026Article
- BOGO: A Proteome-Wide Gene Overexpression Platform for Discovering Rational Cancer Combination Therapies.bioRxiv : the preprint server for biology · 2025Article
- The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1/Raf/MEK pathway-mediated MYC downregulation.Translational oncology · 2025Article
- The XPO1 Inhibitor Eltanexor Modulates the Wnt/β-Catenin Signaling Pathway to Reduce Colorectal Cancer Tumorigenesis.Cancer research communications · 2025Article
- Targeting colorectal cancer at the level of nuclear pore complex.Journal of advanced research · 2025Review
- Positive Feedback Regulation between KLF5 and XPO1 Promotes Cell Cycle Progression of Basal like Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prognostic and functional role of the nuclear export receptor 1 (XPO1) in gastrointestinal cancers: a potential novel target?Molecular biology reports · 2024Review
- The nuclear export protein exportin-1 in solid malignant tumours: From biology to clinical trials.Clinical and translational medicine · 2024Review
- Targeting ATR in patients with cancer.Nature reviews. Clinical oncology · 2024Review
- KPT330 promotes the sensitivity of glioblastoma to olaparib by retaining SQSTM1 in the nucleus and disrupting lysosomal function.Autophagy · 2024Article
- Therapeutic targeting of nuclear export and import receptors in cancer and their potential in combination chemotherapy.IUBMB life · 2024Review
- Targeting crosstalk of STAT3 between tumor-associated M2 macrophages and Tregs in colorectal cancer.Cancer biology & therapy · 2023Article
- Meta‑analysis of the autophagy‑associated protein LC3 as a prognostic marker in colorectal cancer.Experimental and therapeutic medicine · 2023Article
- Cocktail hepatocarcinoma therapy by a super-assembled nano-pill targeting XPO1 and ATR synergistically.Journal of pharmaceutical analysis · 2023Article
- Targeting XPO6 inhibits prostate cancer progression and enhances the suppressive efficacy of docetaxel.Discover oncology · 2023Article
- Patient-derived xenograft model in colorectal cancer basic and translational research.Animal models and experimental medicine · 2023Review
- USP14 promotes the malignant progression and ibrutinib resistance of mantle cell lymphoma by stabilizing XPO1.International journal of medical sciences · 2023Article
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Authors and funding
35 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsUnderstanding the mechanisms by which tumors adapt to therapy is critical for developing effective combination therapeutic approaches to improve clinical outcomes for patients with cancer.
methodsTo identify promising and clinically actionable targets for managing colorectal cancer (CRC), we conducted a patient-centered functional genomics platform that includes approximately 200 genes and paired this with a high-throughput drug screen that includes 262 compounds in four patient-derived xenografts (PDXs) from patients with CRC.
resultsBoth screening methods identified exportin 1 (XPO1) inhibitors as drivers of DNA damage-induced lethality in CRC. Molecular characterization of the cellular response to XPO1 inhibition uncovered an adaptive mechanism that limited the duration of response in TP53-mutated, but not in TP53-wild-type CRC models. Comprehensive proteomic and transcriptomic characterization revealed that the ATM/ATR-CHK1/2 axes were selectively engaged in TP53-mutant CRC cells upon XPO1 inhibitor treatment and that this response was required for adapting to therapy and escaping cell death. Administration of KPT-8602, an XPO1 inhibitor, followed by AZD-6738, an ATR inhibitor, resulted in dramatic antitumor effects and prolonged survival in TP53-mutant models of CRC.
conclusionsOur findings anticipate tremendous therapeutic benefit and support the further evaluation of XPO1 inhibitors, especially in combination with DNA damage checkpoint inhibitors, to elicit an enduring clinical response in patients with CRC harboring TP53 mutations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.