ArticleScience translational medicine2011
Off-target lapatinib activity sensitizes colon cancer cells through TRAIL death receptor up-regulation.
Article in Science translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Characteristics of Prognostic Programmed Cell Death-Related Long Noncoding RNAs Associated With Immune Infiltration and Therapeutic Responses to Colon Cancer.Frontiers in immunology · 2022Trial
- Lapatinib induces ferroptosis in osteosarcoma via the SLC1A5-GPX4 axis.Journal of bone oncology · 2026Article
- Rapamycin Partially Reverts Cavernoma Endothelial Cell Phenotype and, When Combined With Lapatinib, Ameliorates Chronic Lesions.Journal of cellular and molecular medicine · 2026Article
- Phosphoproteomic analysis reveals the diversity of signaling behind ErbB-inhibitor-induced phenotypes.The FEBS journal · 2025Article
- Disrupting DDB2-DNA Interaction by Lapatinib Enhances Chemotherapy Sensitivity.International journal of biological sciences · 2025Article
- Construction and Validation of a Reliable Disulfidptosis-Related LncRNAs Signature of the Subtype, Prognostic, and Immune Landscape in Colon Cancer.International journal of molecular sciences · 2023Article
- Hypothesis-generating proteome perturbation to identify NEU-4438 and acoziborole modes of action in the African Trypanosome.iScience · 2022Article
- AF8c, a Multi-Kinase Inhibitor Induces Apoptosis by Activating DR5/Nrf2 via ROS in Colorectal Cancer Cells.Cancers · 2022Article
- Sensitizing TRAIL‑resistant A549 lung cancer cells and enhancing TRAIL‑induced apoptosis with the antidepressant amitriptyline.Oncology reports · 2021Article
- How Physiologic Targets Can Be Distinguished from Drug-Binding Proteins.Molecular pharmacology · 2021Article
- Death receptor 5 contributes to cardiomyocyte hypertrophy through epidermal growth factor receptor transactivation.Journal of molecular and cellular cardiology · 2019Article
- Development of acquired resistance to lapatinib may sensitise HER2-positive breast cancer cells to apoptosis induction by obatoclax and TRAIL.BMC cancer · 2018Article
- The K-Ras effector p38γ MAPK confers intrinsic resistance to tyrosine kinase inhibitors by stimulatingThe Journal of biological chemistry · 2017Article
- Novel multi-targeted ErbB family inhibitor afatinib blocks EGF-induced signaling and induces apoptosis in neuroblastoma.Oncotarget · 2017Article
- Ginsenoside compound K sensitizes human colon cancer cells to TRAIL-induced apoptosis via autophagy-dependent and -independent DR5 upregulation.Cell death & disease · 2016Article
- Delivery of tumor-homing TRAIL sensitizer with long-acting TRAIL as a therapy for TRAIL-resistant tumors.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Identification of therapeutic targets in ovarian cancer through active tyrosine kinase profiling.Oncotarget · 2015Article
- New benzimidazole acridine derivative induces human colon cancer cell apoptosis in vitro via the ROS-JNK signaling pathway.Acta pharmacologica Sinica · 2015Article
- A benzimidazole derivative exhibiting antitumor activity blocks EGFR and HER2 activity and upregulates DR5 in breast cancer cells.Cell death & disease · 2015Article
- Blocks to thyroid cancer cell apoptosis can be overcome by inhibition of the MAPK and PI3K/AKT pathways.Cell death & disease · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Lapatinib, a dual HER2/EGFR (human epidermal growth factor receptor 2/epidermal growth factor receptor) inhibitor, is a recently approved targeted therapy for metastatic breast cancer. Because lapatinib enhances the efficacy of the chemotherapeutic agent capecitabine in breast cancer patients, we tested whether lapatinib also enhances the activity of anticancer agents in colorectal cancer. We found that lapatinib improved the proapoptotic effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and two TRAIL receptor agonists, the antibodies mapatumumab and lexatumumab. Tumors from mice treated with a combination of lapatinib and TRAIL exhibited more immunostaining for cleaved caspase-8, a marker of the extrinsic cell death pathway, than did tumors from mice treated with lapatinib or TRAIL alone. Furthermore, combination therapy suppressed tumor growth more effectively than either agent alone. Lapatinib up-regulated the proapoptotic TRAIL death receptors DR4 and DR5, leading to more efficient induction of apoptosis in the presence of TRAIL receptor agonists. This activity of lapatinib was independent of EGFR and HER2. The off-target induction of DR5 by lapatinib resulted from activation of the c-Jun amino-terminal kinase (JNK)/c-Jun signaling axis. This activity of lapatinib on TRAIL death receptor expression and signaling may confer therapeutic benefit when increased doses of lapatinib are used in combination with TRAIL receptor-activating agents.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.