Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (644 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A piperidine and aminopyridine derivative that acts as an inhibitor of receptor protein-tyrosine kinases, including anaplastic lymphoma kinase (ALK) and hepatocyte growth factor receptor (HGFR; c-Met). It is used in the treatment of non-small cell lung cancer.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: PF-02341066; PF 02341066; PF02341066; PF-2341066; PF2341066; PF 2341066; Xalkori.
Where it fits in the MeSH classification
- Broader topics
- Piperidines; Aminopyridines
Related concepts
- Receptor Protein-Tyrosine Kinases
- Anaplastic Lymphoma Kinase
- Hepatocyte Growth Factor Receptor
- Non-Small Cell Lung Cancer
Research landscape
PubMed indexes 1,939 records tagged with the MeSH heading “Crizotinib” (counts retrieved 2026-10-31). 705 of them (36.4%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 1,257 records.
Reviews account for 238 records (12.3%) and meta-analyses for 27. Randomized controlled trials number 61 (3.1%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 3 |
| 2010-2019 | 1,257 |
| 2020 onward | 705 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 238 | 12.3% |
| Meta-analyses | 27 | 1.4% |
| Randomized controlled trials | 61 | 3.1% |
Method: PubMed query "Crizotinib"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Crizotinib-induced immunogenic cell death in non-small cell lung cancer | 2019 | Research article Design not recorded in structured metadata | 262 | cc by PMID 30940805 · DOI · PMC6445096 |
| The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models | 2019 | Research article Design not recorded in structured metadata | 115 | cc by PMID 31399568 · DOI · PMC6688997 |
| Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines | 2017 | Research article Design not recorded in structured metadata | 58 | cc by PMID 28680140 · DOI · PMC5498486 |
| Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity | 2025 | Research article Design not recorded in structured metadata | 8 | cc by PMID 39836491 · DOI · PMC11984922 |
Crizotinib-induced immunogenic cell death in non-small cell lung cancer [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses.
- Closing excerpt
- Hence, a sequential combination treatment consisting in conventional chemotherapy together with crizotinib, followed by immune checkpoint blockade may be active against NSCLC.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (151 words)
Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses. Here we unravel the results of an unbiased screen identifying high-dose (10 µM) crizotinib as an ICD-inducing tyrosine kinase inhibitor that has exceptional antineoplastic activity when combined with non-ICD inducing chemotherapeutics like cisplatin. The combination of cisplatin and high-dose crizotinib induces ICD in non-small cell lung carcinoma (NSCLC) cells and effectively controls the growth of distinct (transplantable, carcinogen- or oncogene induced) orthotopic NSCLC models. These anticancer effects are linked to increased T lymphocyte infiltration and are abolished by T cell depletion or interferon-γ neutralization. Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies. Hence, a sequential combination treatment consisting in conventional chemotherapy together with crizotinib, followed by immune checkpoint blockade may be active against NSCLC.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30940805 · DOI · PMC6445096
The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models [2]
Abstract reading summary — source excerpts
- Opening excerpt
- ROS1 gene rearrangement was observed in around 1-2 % of NSCLC patients and in several other cancers such as cholangiocarcinoma, glioblastoma, or colorectal cancer.
- Closing excerpt
- Here we report that DS-6051b is effective in treating ROS1- or NTRK-rearranged cancer in preclinical models, including crizotinib-resistant ROS1 positive cancer with secondary kinase domain mutations especially G2032R mutation which is highly resistant to crizotinib as well as lorlatinib and entrectinib, next generation ROS1 inhibitors.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (148 words)
ROS1 gene rearrangement was observed in around 1-2 % of NSCLC patients and in several other cancers such as cholangiocarcinoma, glioblastoma, or colorectal cancer. Crizotinib, an ALK/ROS1/MET inhibitor, is highly effective against ROS1-rearranged lung cancer and is used in clinic. However, crizotinib resistance is an emerging issue, and several resistance mechanisms, such as secondary kinase-domain mutations (e.g., ROS1-G2032R) have been identified in crizotinib-refractory patients. Here we characterize a new selective ROS1/NTRK inhibitor, DS-6051b, in preclinical models of ROS1- or NTRK-rearranged cancers. DS-6051b induces dramatic growth inhibition of both wild type and G2032R mutant ROS1-rearranged cancers or NTRK-rearranged cancers in vitro and in vivo. Here we report that DS-6051b is effective in treating ROS1- or NTRK-rearranged cancer in preclinical models, including crizotinib-resistant ROS1 positive cancer with secondary kinase domain mutations especially G2032R mutation which is highly resistant to crizotinib as well as lorlatinib and entrectinib, next generation ROS1 inhibitors.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31399568 · DOI · PMC6688997
Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines [3]
Abstract reading summary — source excerpts
- Opening excerpt
- CIC-DUX4 sarcoma (CDS) is a group of rare, mesenchymal, small round cell tumours that harbour the unique CIC-DUX4 translocation, which causes aberrant gene expression.
- Closing excerpt
- Our models will be useful modalities to develop novel therapeutic strategies against CDS.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (182 words)
CIC-DUX4 sarcoma (CDS) is a group of rare, mesenchymal, small round cell tumours that harbour the unique CIC-DUX4 translocation, which causes aberrant gene expression. CDS exhibits an aggressive course and poor clinical outcome, thus novel therapeutic approaches are needed for CDS treatment. Although patient-derived cancer models are an essential modality to develop novel therapies, none currently exist for CDS. Thus, the present study successfully established CDS patient-derived xenografts and subsequently generated two CDS cell lines from the grafted tumours. Notably, xenografts were histologically similar to the original patient tumour, and the expression of typical biomarkers was confirmed in the xenografts and cell lines. Moreover, the xenograft tumours and cell lines displayed high Src kinase activities, as assessed by peptide-based tyrosine kinase array. Upon screening 119 FDA-approved anti-cancer drugs, we found that only actinomycine D and doxorubicin were effectively suppress the proliferation among the drugs for standard therapy for Ewing sarcoma. However, we identified molecular targeting reagents, such as bortezomib and crizotinib that markedly suppressed the growth of CDS cells. Our models will be useful modalities to develop novel therapeutic strategies against CDS.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28680140 · DOI · PMC5498486
Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Metabolic disorders have been identified as one of the causes of drug-induced liver injury; however, the direct regulatory mechanism regarding this disorder has not yet been clarified.
- Closing excerpt
- The autophagy activator known as metformin or the SQLE enzymatic inhibitor known as terbinafine has potential clinical use for alleviating crizotinib hepatotoxicity.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (163 words)
Metabolic disorders have been identified as one of the causes of drug-induced liver injury; however, the direct regulatory mechanism regarding this disorder has not yet been clarified. In this study, a single regulatory mechanism of small molecule kinase inhibitors, with crizotinib as the representative drug is elucidated. First, it is discovered that crizotinib induced aberrant lipid metabolism and apoptosis in the liver. A mechanistic study revealed that crizotinib treatment promoted the accumulation of squalene epoxidase (SQLE) by inhibiting autophagosome-lysosome fusion which blocked the autophagic degradation of SQLE. A maladaptive increase in SQLE led to disturbances in cholesterol and sphingolipid metabolism via an enzymatic activity-dependent manner. Abnormal cholesterol results in both steatosis and inflammatory infiltration, and disturbances in sphingolipid metabolism promote cell apoptosis by inducing lysosomal membrane permeabilization. The restoration of the level or activity of SQLE ameliorated steatosis and hepatocyte injury. The autophagy activator known as metformin or the SQLE enzymatic inhibitor known as terbinafine has potential clinical use for alleviating crizotinib hepatotoxicity.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39836491 · DOI · PMC11984922
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Crizotinib in ALK+ inflammatory myofibroblastic tumors-Current experience and future perspectives [5]
- Research article Targeting ROS1 Rearrangements in Non-small Cell Lung Cancer: Crizotinib and Newer Generation Tyrosine Kinase Inhibitors [6]
- Research article Resistance mechanisms and potent-targeted therapies of ROS1-positive lung cancer [7]
- Research article Clinical Pharmacokinetics of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer [8]
- Research article Efficacy and Safety of Crizotinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with ROS1 Rearrangement or MET Alteration: A Systematic Review and Meta-Analysis [9]
- Research article Gastric cancer patient with c-MET amplification treated with crizotinib after failed multi-line treatment: A case report and literature review [10]
References
- Liu P, Zhao L, Pol J, Levesque S, Petrazzuolo A, Pfirschke C, et al.. Crizotinib-induced immunogenic cell death in non-small cell lung cancer. . 2019. PMID 30940805 · DOI · PMC6445096
- Katayama R, Gong B, Togashi N, Miyamoto M, Kiga M, Iwasaki S, et al.. The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. . 2019. PMID 31399568 · DOI · PMC6688997
- Oyama R, Takahashi M, Yoshida A, Sakumoto M, Takai Y, Kito F, et al.. Generation of novel patient-derived CIC- DUX4 sarcoma xenografts and cell lines. . 2017. PMID 28680140 · DOI · PMC5498486
- Yan H, Huang X, Zhou Y, Mu Y, Zhang S, Cao Y, et al.. Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity. . 2025. PMID 39836491 · DOI · PMC11984922
- Theilen TM, Soerensen J, Bochennek K, Becker M, Schwabe D, Rolle U, et al.. Crizotinib in ALK+ inflammatory myofibroblastic tumors-Current experience and future perspectives. Pediatr Blood Cancer. 2018. PMID 29286567 · DOI
- Morris TA, Khoo C, Solomon BJ. Targeting ROS1 Rearrangements in Non-small Cell Lung Cancer: Crizotinib and Newer Generation Tyrosine Kinase Inhibitors. Drugs. 2019. PMID 31313100 · DOI
- Roys A, Chang X, Liu Y, Xu X, Wu Y, Zuo D. Resistance mechanisms and potent-targeted therapies of ROS1-positive lung cancer. Cancer Chemother Pharmacol. 2019. PMID 31256210 · DOI
- Hirota T, Muraki S, Ieiri I. Clinical Pharmacokinetics of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer. Clin Pharmacokinet. 2019. PMID 29915924 · DOI
- Vuong HG, Nguyen TQ, Nguyen HC, Nguyen PT, Ho ATN, Hassell L. Efficacy and Safety of Crizotinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with ROS1 Rearrangement or MET Alteration: A Systematic Review and Meta-Analysis. Target Oncol. 2020. PMID 32865687 · DOI
- Hou GX, Song BB. Gastric cancer patient with c-MET amplification treated with crizotinib after failed multi-line treatment: A case report and literature review. Math Biosci Eng. 2019. PMID 31499745 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.