A Systematic Review of Mesenchymal Epithelial Transition Factor (MET) and Its Impact in the Development and Treatment of Non-Small-Cell Lung Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Search Strategy
2.2. Exclusion and Inclusion Criteria
2.3. Data Extraction and Processing
3. Bias
4. Results
4.1. Epidemiology
4.2. Prevalence of Aberrant MET Expression
4.3. Targeted Therapies
5. Discussion
6. Strengths and Limitations
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
Appendix A
Search Queries
Appendix B
Section and Topic | Item # | Checklist Item | Location Where Item Is Reported |
---|---|---|---|
TITLE | |||
Title | 1 | Identify the report as a systematic review. | Page 1 |
ABSTRACT | |||
Abstract | 2 | See the PRISMA 2020 for Abstracts checklist. | Page 1, paragraph 2 |
INTRODUCTION | |||
Rationale | 3 | Describe the rationale for the review in the context of existing knowledge. | Page 2, paragraph 2 |
Objectives | 4 | Provide an explicit statement of the objective(s) or question(s) the review addresses. | Page 4, paragraph 2 |
METHODS | |||
Eligibility criteria | 5 | Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses. | Page 5, paragraph 2 |
Information sources | 6 | Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted. | Page 5, paragraph 1 |
Search strategy | 7 | Present the full search strategies for all databases, registers and websites, including any filters and limits used. | Page 22 |
Selection process | 8 | Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process. | Page 5, paragraph 2 |
Data collection process | 9 | Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process. | Page 5, paragraph 2 |
Data items | 10a | List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g., for all measures, time points, analyses), and if not, the methods used to decide which results to collect. | Page 6, paragraph 1 |
10b | List and define all other variables for which data were sought (e.g., participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information. | Page 6, paragraph 1 | |
Study risk of bias assessment | 11 | Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process. | Page 11, paragraph 1 |
Effect measures | 12 | Specify for each outcome the effect measure(s) (e.g., risk ratio, mean difference) used in the synthesis or presentation of results. | N/A |
Synthesis methods | 13a | Describe the processes used to decide which studies were eligible for each synthesis (e.g., tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)). | Page 8, Table 3 |
13b | Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions. | N/A | |
13c | Describe any methods used to tabulate or visually display results of individual studies and syntheses. | Page 8, Table 3 | |
13d | Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used. | N/A | |
13e | Describe any methods used to explore possible causes of heterogeneity among study results (e.g., subgroup analysis, meta-regression). | N/A | |
13f | Describe any sensitivity analyses conducted to assess robustness of the synthesized results. | N/A | |
Reporting bias assessment | 14 | Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). | Page 11, paragraph 1 |
Certainty assessment | 15 | Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. | N/A |
RESULTS | |||
Study selection | 16a | Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram. | Page 6, Figure 3 |
16b | Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded. | N/A | |
Study characteristics | 17 | Cite each included study and present its characteristics. | Page 11, paragraph 4 |
Risk of bias in studies | 18 | Present assessments of risk of bias for each included study. | Pages 27–28 |
Results of individual studies | 19 | For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g., confidence/credible interval), ideally using structured tables or plots. | Pages 29–30 |
Results of syntheses | 20a | For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies. | Page 21, paragraph 2 |
20b | Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the summary estimate and its precision (e.g., confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect. | N/A | |
20c | Present results of all investigations of possible causes of heterogeneity among study results. | Page 21, paragraph 2 | |
20d | Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results. | N/A | |
Reporting biases | 21 | Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed. | Pages 27–28 |
Certainty of evidence | 22 | Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed. | N/A |
DISCUSSION | |||
Discussion | 23a | Provide a general interpretation of the results in the context of other evidence. | Page 18, paragraph 1 |
23b | Discuss any limitations of the evidence included in the review. | Page 21, paragraph 2 | |
23c | Discuss any limitations of the review processes used. | Page 21, paragraph 2 | |
23d | Discuss implications of the results for practice, policy, and future research. | Page 18, paragraph 3 | |
OTHER INFORMATION | |||
Registration and protocol | 24a | Provide registration information for the review, including register name and registration number, or state that the review was not registered. | Page 5, paragraph 1 |
24b | Indicate where the review protocol can be accessed, or state that a protocol was not prepared. | Page 5, paragraph 1 | |
24c | Describe and explain any amendments to information provided at registration or in the protocol. | N/A | |
Support | 25 | Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review. | Page 22 |
Competing interests | 26 | Declare any competing interests of review authors. | Page 22 |
Availability of data, code and other materials | 27 | Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review. | Page 22 |
Topic | No. | Item | Reported? |
---|---|---|---|
TITLE | |||
Title | 1 | Identify the report as a systematic review. | Yes |
BACKGROUND | |||
Objectives | 2 | Provide an explicit statement of the main objective(s) or question(s) the review addresses. | Yes |
METHODS | |||
Eligibility criteria | 3 | Specify the inclusion and exclusion criteria for the review. | No |
Information sources | 4 | Specify the information sources (e.g., databases, registers) used to identify studies and the date when each was last searched. | Yes |
Risk of bias | 5 | Specify the methods used to assess risk of bias in the included studies. | No |
Synthesis of results | 6 | Specify the methods used to present and synthesize results. | No |
RESULTS | |||
Included studies | 7 | Give the total number of included studies and participants and summarise relevant characteristics of studies. | Yes |
Synthesis of results | 8 | Present results for main outcomes, preferably indicating the number of included studies and participants for each. If meta-analysis was done, report the summary estimate and confidence/credible interval. If comparing groups, indicate the direction of the effect (i.e., which group is favoured). | Yes |
DISCUSSION | |||
Limitations of evidence | 9 | Provide a brief summary of the limitations of the evidence included in the review (e.g., study risk of bias, inconsistency and imprecision). | No |
Interpretation | 10 | Provide a general interpretation of the results and important implications. | Yes |
OTHER | |||
Funding | 11 | Specify the primary source of funding for the review. | No |
Registration | 12 | Provide the register name and registration number. | Yes |
Appendix C
Mutational Status | Median Age (Years) | Male Gender (%) | History of No Smoking (%) | |
---|---|---|---|---|
Arrieta et al., 2016 [1] | EGFR+/WT | 60.1 | 33.3% | 39.4% |
Han et al., 2017 [14] | EGFR+/WT, MET+/− | Treatment: 63.0 Placebo: 63.0 | Treatment: 56.0% Placebo: 57.0% | Treatment: 18.5% Placebo: 15.8% |
Helman et al., 2018 [25] | EGFR+ | 61.0 | 28.6% | NS |
Hirsch et al., 2017 [17] | MET+/− | Treatment: 68.0 Placebo: 66.0 | Treatment: 70.9% Placebo: 74.1% | Treatment: 3.6% Placebo: 5.6% |
Jänne et al., 2016 [21] | EGFR+/WT | 59.5 | 39.0% | 51.0% |
Kishi et al., 2019 [15] | EGFR+ MET+ | 67.0 | 43% | NS |
Landi et al., 2019 [18] | EGFR WT MET+ | 56.0 | 65% | 23% |
Matsumoto et al., 2014 [19] | EGFR WT | 64.0 | 19.7% | 89.1% |
Moro-Sibilot et al., 2019 [29] | EGFR+/WT MET+/− | MET amplified: 59.0 MET mutated: 72.0 | MET amplified: 56.0% MET mutated: 32.0% | MET amplified: 24.0% MET mutation: 48.0% |
Neal et al., 2016 [2] | EGFR WT | 65.3 | 45.0% | 15% |
Okamoto et al., 2014 [3] | NS | 64.0 | 77.0% | 18.0% |
Ou et al., 2017 [24] | NS | 60.0 | 30.0% | 52.0% |
Palmero et al., 2021 [11] | NS | 64.3 | 65.0% | 27.0% |
Sacher et al., 2016 [28] | EGFR+/WT | 64.0 | 45.0% | 18.0% |
Scagliotti et al., 2018 [30] | EGFR+ MET+/− | Treatment: 59.5 Placebo: 65.0 | Treatment: 42.9% Placebo: 47.2% | Treatment: 48.2% Placebo: 60.4% |
Schuler et al., 2020 [20] | EGFR WT MET+ | 60.0 | 60.0% | NS |
Sequist et al., 2020 [22] | EGFR+ MET+ | Cohort B: 59.0 Cohort D: 62.0 | Cohort B: 59% Cohort D: 60% | NS |
Seto et al., 2021 [31] | EGFR WT MET+ | 68.0 | 66.7% | 42.2% |
Spigel et al., 2013 [6] | EGFR+/WT MET+/− | Treatment MET-: 63.0 Placebo MET-: 61.0 Treatment MET+: 66.0 Placebo MET+: 64.0 | Treatment MET-: 65.0% Placebo MET-: 55.0% Treatment MET+: 51.0% Placebo MET+: 65.0% | Treatment MET -: 7.0% Placebo MET -: 3.0% Treatment MET+: 20.0% Placebo MET+: 19.0% |
Wakelee et al., 2017 [32] | EGFR+/WT MET+/− | Cohort I treatment: 60.0 Cohort I placebo: 60.5 Cohort II treatment: 66.0 Cohort II placebo: 63.0 | Cohort I treatment: 68.1% Cohort I placebo: 48.6% Cohort II treatment: 55.9% Cohort II placebo: 42.6% | Cohort I treatment: 21.7% Cohort I placebo: 25.7% Cohort II treatment: 27.1% Cohort II placebo: 13.1% |
Wu et al., 2020 [23] | EGFR+ MET+ | Phase Ib: 65.5 Phase II treatment: 61.0 Phase II placebo: 58.3 | Phase Ib: 44.0% Phase II treatment: 35.5% Phase II placebo: 50.0% | Phase Ib: 72.0% Phase II treatment: 68.0% Phase II placebo: 67.0% |
Yoshioka et al., 2015 [5] | EGFR WT MET+/− | Treatment: 63.0 Placebo: 63.0 | Treatment: 66.7% Placebo: 70.8% | Treatment: 25.5% Placebo: 26.2% |
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Drug Name | Effect | References |
---|---|---|
Afatinib | Binds covalently and irreversibly to the kinase domain of EGFR. | Arrieta et al. [1] |
Cabozantinib | A small molecule TKI that targets MET, VEGFR2, RET, ROS1, KIT, TIE-2, and AXL. Binds intracellularly to MET. | Neal et al. [2] Landi et al. [18] |
Capmatinib | A highly selective intracellular MET inhibitor. | Schuler et al. [20] Sequist et al. [22] |
Crizotinib | An intracellular MET/ALK/ROS1 RTK inhibitor with high specificity for MET. | Landi et al. [18] |
Dacomitinib | A small irreversible pan-human EGFR inhibitor. | Jänne et al. [21] |
Erlotinib | A reversible, small-molecule EGFR TKI. | Spigel et al. [6] |
Gefitinib | A reversible EGFR TKI. | Arrieta et al. [1] Wu et al. [23] |
Onartuzumab | A recombinant, fully humanized, one-armed anti-MET monovalent monoclonal antibody. Binds to the extracellular domain of MET without activating it and without dimerizing. | Hirsch et al. [17] Kishi et al. [15] |
Osimertinib | A CNS-active, irreversible EGFR TKI. | Sequist et al. [22] |
Rociletinib | An irreversible EGFR TKI targeting mutated form of the EGFR gene. | Arrieta et al. [1] |
Savolitinib | A small molecule, ATP competitive, selective MET TKI. | Sequist et al. [22] |
Tepotinib | A highly selective, ATP competitive MET inhibitor. | Wu et al. [23] |
Tivantinib | A selective, non-ATP-competitive MET inhibitor metabolized by CYP2C19. | Yoshioka et al. [5] |
Total Participants | Cancer Type | Mutational Status | Active Drug | Results | |
---|---|---|---|---|---|
Arrieta et al., 2016 [1] | n = 66 | NSCLC | EGFR WT EGFR+ | Afatinib (EGFR TKI) | Reduced levels of HGF led to improved ORR, PFS, and OS. |
Helman et al., 2018 [25] | n = 77 | NSCLC | EGFR+ | Rociletinib (EGFR TKI) | Prevalence of MET alteration was 15.0%. MET amplification was seen in 7.6% of these, 4.5% had focal amplification, and 3.1% had aneuploidy. |
Matsumoto et al., 2014 [19] | n = 47 | NSCLC | EGFR WT | Erlotinib (EGFR TKI) | Expression of HGF resulted in poor response to erlotinib with shorter PFS. MET mutational status did not correlate to response to erlotinib or PFS. |
Okamoto et al., 2014 [3] | n = 295 | NSCLC | NS | Chemotherapy | Totally, 21 patients (7.6%) had MET mutations. MET amplifications were present in 9 (3.9%) cases. Median GCN was 8.8 among MET amplified patients. |
Palmero et al., 2021 [11] | n = 186 | NSCLC | NS | None | Totally, 22.0% of patients had MET amplifications and 11.0% had METex14 mutations. |
Sacher et al., 2016 [28] | n = 22 | NSCLC | EGFR WT EGFR+ | Erlotinib | Totally, 45.0% of subjects harbored a MET alteration. MET amplification was present in 9.0% of the patients. |
Study Design | Total Participants | Cancer Type | Mutational Status | Definition of MET+ | Active Drug | Results | |
---|---|---|---|---|---|---|---|
Han et al., 2017 [14] | Phase III | n = 636 | NSCLC | EGFR+/WT, MET+/− | Not defined | Onartuzumab (MET TKI) + erlotinib (EGFR TKI) vs. erlotinib | High dose onartuzumab resulted in longer PFS (4.4 months) compared to low dose (2.5 months) and erlotinib (2.5 months). No significant difference in OS. |
Hirsch et al., 2017 [17] | Phase II | n = 106 | NSCLC | MET+/− | MET IHC2+ or IHC3+ | Onartuzumab (MET TKI) + chemotherapy vs. chemotherapy + placebo | Median PFS was 5 months for onartuzumab and 5.2 months for placebo (ns). Median OS was 10.8 months for onartuzumab and 7.9 months for placebo (ns). |
Jänne et al., 2016 [21] | Phase I | n = 67 | NSCLC | EGFR+/WT | MET IHC2+ or IHC3+, MET GCN ≥ 2.1 | Crizotinib (MET TKI) + dacomitinib (EGFR TKI) | Median PFS was 3 months with 61.0% stable disease in the escalation phase. Median PFS was 2.1 months with 32.0% stable disease in the expansion phase. |
Kishi et al., 2019 [15] | Phase II | n = 61 | NSCLC | EGFR+ MET+ | MET IHC2+ or IHC3+, the total number of MET genes in 20 cancer cells ≥ 90 | Onartuzumab (MET TKI) + erlotinib (EGFR TKI) | Median PFS was 8.5 months, median OS 15.6 months, and ORR 68.9%. |
Landi et al., 2019 [18] | Phase II | n = 26 | NSCLC | EGFR WT MET+ | MET-CEP7/ratio ≥ 2.2, METex14 mutation | Crizotinib (MET TKI) | ORR of 27.0%, median PFS 4.4 months, and median OS 5.4 months. |
Moro-Sibilot et al., 2019 [29] | Phase II | n = 53 | NSCLC | EGFR WT EGFR+ MET+/− | MET IHC2+ or IHC3+, MET GCN ≥ 6, MET exon skipping mutations in exon 14, 16–19 determined by NGS | Crizotinib (MET TKI) | ORR of 16.0%, median PFS of 3.2 months, and median OS of 7.7 months in the MET GCN ≥ 6 cohort. ORR of 10.7%, median PFS of 2.4 months, and median OS of 8.1 months in the MET mutated cohort. |
Neal et al., 2016 [2] | Phase II | n = 111 | NSCLC | EGFR WT | Tested through IHC, positive if MET was expressed in either membrane or cytoplasm | Cabozantinib (MET TKI) + erlotinib (EGFR TKI) vs. cabozantinib vs. erlotinib | Median PFS of 1.8 months and OS of 5.1 months for erlotinib. PFS was 4.7 months and OS was 12.3 months for erlotinib + cabozantinib. PFS was 4.3 months and OS was 9.2 months (ns) for cabozantinib. No association between MET IHC+ and PFS in the cabozantinib group. |
Ou et al., 2017 [24] | Phase I | n = 26 | NSCLC | NS | Mutational status not mentioned | Crizotinib (MET TKI) + erlotinib (EGFR TKI) | Two patients had partial response, 8 had stable disease, and 10 had progressive disease. |
Scagliotti et al., 2018 [30] | Phase III | n = 109 | NSCLC | EGFR+ MET+/− | MET IHC2+ or IHC3+, MET GCN ≥ 4 | Tivantinib (MET TKI) + erlotinib (EGFR TKI) vs. erlotinib + placebo | Greater overall response rate (60.7%) and median PFS (13.0 months) for tivantinib + erlotinib compared to erlotinib + placebo (43.4%, 7.5 months). Similar median OS between groups (25.5 months for tivantinib and 20.3 months for placebo). |
Schuler et al., 2020 [20] | Phase I | n = 55 | NSCLC | EGFR WT MET+ | MET H-score ≥ 150, MET/CEP7 ≥ 2.0, MET GCN ≥ 5, MET IHC 2+ or IHC3+ | Capmatinib (MET TKI) | Median PFS was 3.7 months. In patients with MET GCN ≥ 6 median PFS was 9.3 months. |
Sequist et al., 2020 [22] | Phase Ib | n = 180 | NSCLC | EGFR+ MET+ | MET GCN ≥ 5, MET/CEP7 ratio ≥ 2, MET IHC3+ or ≥20.0% tumor cells in NGS | Savolitinib (MET TKI) + osimertinib (EGFR TKI) | Partial response in 89 patients treated with savolitinib and osimertinib. PFS was 7.6 months and 9.1 months in two different subgroups. |
Seto et al., 2021 [31] | Phase II | n = 45 | NSCLC | EGFR WT MET+ | METex14 mutation, MET amplification | Capmatinib (MET TKI) | In a subcohort with METex14 mutations receiving second or third-line (2/3L) treatment with capmatinib, overall response rate was 36.4%. In a second cohort with MET GCN ≥ 10, overall response rate to 2/3L capmatinib was 45.5%. |
Spigel et al., 2013 [6] | Phase II | n = 136 | NSCLC | EGFR+/WT MET+/− | MET IHC2+ or IHC3+ | Onartuzumab (MET TKI) + erlotinib (EGFR TKI) vs. erlotinib | No difference in PFS and OS between groups. In a MET+ subgroup, PFS was significantly longer for onartuzumab compared to erlotinib + placebo (2.9 vs. 1.5 months). Longer OS in the MET+ subgroup receiving onartuzumab (12.6 vs. 3.8 months). |
Wakelee et al., 2017 [32] | Phase II | n = 259 | NSCLC | EGFR+/WT MET+/− | MET IHC2+ or ICH3+ | Cohort 1: onartuzumab (MET TKI) + bevacizumab (VEGF-A TKI) + chemotherapy vs. placebo + bevacizumab + chemotherapy. Cohort 2: onartuzumab + chemotherapy vs. placebo + chemotherapy | Cohort 1: longer median PFS on placebo (6.8 months) compared to onartuzumab (5.0 months). A MET+ subgroup had a median PFS of 4.8 months and OS of 9.9 months on onartuzumab vs. 6.9 months and 16.5 months on placebo. Cohort 2: median PFS of 4.9 months and median OS of 8.5 months on onartuzumab vs. 5.1 months and 13.7 months on placebo. In a MET+ subgroup, median PFS was 5.0 months and OS was 8.0 months on onartuzumab vs. 5.0 months and 7.6 months on placebo. |
Wu et al., 2020 [23] | Phase Ib/II | n = 55 | NSCLC | EGFR+ MET+ | MET IHC2+ or IHC3+, MET GCN ≥ 5 | Tepotinib (MET TKI) + gefitinib (EGFR TKI) vs. chemotherapy | Significantly longer OS (37.3 months vs. 13.1 months) and PFS (16.6 months vs. 4.2 months) for tepotinib + gefitinib in patients with MET IHC3+ or MET GCN ≥ 5. |
Yoshioka et al., 2015 [5] | Phase III | n = 303 | NSCLC | EGFR WT MET+/− | IHC with moderate/strong intensity ≥ 50.0% of tumor cells, MET GCN ≥ 4 | Tivantinib (MET TKI) + erlotinib (EGFR TKI) vs. erlotinib + placebo | Significantly longer PFS for tivantinib + erlotinib (2.9 months) compared to erlotinib + placebo (2 months). No effect on OS. |
Clinical Trial ID | Study Design | Study Type | Total Participants | Cancer Type | Mutational Status | Active Drug and Effect |
---|---|---|---|---|---|---|
NCT02544633 | Phase II | Non-randomized | n = 68 | NSCLC | MET activating mutation MET amplification | MGCD265: oral RTK inhibitor targeting MET |
NCT02920996 | Phase II | Single arm | n = 12 | NSCLC | METex14 mutation | Merestinib: reversible type II ATP-competitive MET inhibitor |
NCT02896231 | Phase I | Dose escalation | n = 37 | NSCLC | MET+ | PLB1001: selective MET inhibitor |
NCT04270591 | Phase Ib/II | Single arm | n = 183 | NSCLC | METex14 mutation MET amplification MET overexpression | Glumetinib: selective MET inhibitor |
NCT02648724 | Phase I/II | Non-randomized | n = 57 | NSCLC | MET amplification METex14 deletion | Sym015: monoclonal antibody mixture targeting MET |
NCT03539536 | Phase II | Single arm | n = 275 | NSCLC | MET+ | Telisotuzumab vedotin: antibody-drug conjugate targeting MET |
NCT02609776 | Phase I | Non-randomized | n = 780 | Advanced NSCLC | Varying | Amivantamab: human bispecific antibody targeting EGFR and MET |
NCT04077099 | Phase I/II | Single arm | n = 82 | NSCLC | Any MET alteration | REGN5093: human bispecific antibody targeting MET, inducing internalization and degradation |
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Bodén, E.; Sveréus, F.; Olm, F.; Lindstedt, S. A Systematic Review of Mesenchymal Epithelial Transition Factor (MET) and Its Impact in the Development and Treatment of Non-Small-Cell Lung Cancer. Cancers 2023, 15, 3827. https://doi.org/10.3390/cancers15153827
Bodén E, Sveréus F, Olm F, Lindstedt S. A Systematic Review of Mesenchymal Epithelial Transition Factor (MET) and Its Impact in the Development and Treatment of Non-Small-Cell Lung Cancer. Cancers. 2023; 15(15):3827. https://doi.org/10.3390/cancers15153827
Chicago/Turabian StyleBodén, Embla, Fanny Sveréus, Franziska Olm, and Sandra Lindstedt. 2023. "A Systematic Review of Mesenchymal Epithelial Transition Factor (MET) and Its Impact in the Development and Treatment of Non-Small-Cell Lung Cancer" Cancers 15, no. 15: 3827. https://doi.org/10.3390/cancers15153827