-
Molecular Diagnosis & Therapy Mar 2022Numerous therapeutic agents specifically targeting the mesenchymal-epithelial transition (MET) oncogene are being developed. (Review)
Review
INTRODUCTION
Numerous therapeutic agents specifically targeting the mesenchymal-epithelial transition (MET) oncogene are being developed.
OBJECTIVE
The aim of the current review was to systematically identify and analyze clinical trials that have evaluated MET inhibitors in various cancer types and to provide an overview of their clinical outcomes.
METHODS
An electronic literature search was carried out in the PubMed and Embase databases to identify published clinical trials related to MET inhibitors. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed for the systematic appraisal of the literature. Data related to clinical outcomes, including progression-free survival, overall survival, objective response rate, and overall tumor response, were extracted.
RESULTS
In total, 49 publications were included. Among these, 51.02% were phase II studies, 14.28% were randomized controlled trials, three were phase III studies, two were prospective observational studies, and the remainder were either phase I or Ib studies. The majority (44.89%) of articles reported the clinical outcomes of MET inhibitors, including small molecules, monoclonal antibodies, and other agents, in patients with non-small-cell lung cancer (NSCLC) harboring MET alterations. MET amplification, overexpression, and MET exon 14 skipping mutations were the major MET alteration types reported across the included studies. Clinical responses/outcomes varied considerably.
CONCLUSION
This systematic literature review provides an overview of the literature available in Embase and PubMed regarding MET-targeted therapies. MET-selective tyrosine kinase inhibitors (TKIs) (capmatinib, tepotinib, and savolitinib) may become a new standard of care in NSCLC, specifically with MET exon 14 skipping mutations. A combination of MET TKIs with epidermal growth factor receptor (EGFR) TKIs (osimertinib + savolitinib, tepotinib + gefitinib) may be a potential solution for MET-driven EGFR TKI resistance. Further, MET alteration (MET amplification/overexpression) may be an actionable target in gastric cancer and papillary renal cell carcinoma.
Topics: Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Gefitinib; Humans; Lung Neoplasms; Mutation; Observational Studies as Topic; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met
PubMed: 35266116
DOI: 10.1007/s40291-021-00568-w -
Journal of Thoracic Oncology : Official... Dec 2023Brain metastases (BMs) in patients with advanced and metastatic NSCLC are linked to poor prognosis. Identifying genomic alterations associated with BM development could... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Brain metastases (BMs) in patients with advanced and metastatic NSCLC are linked to poor prognosis. Identifying genomic alterations associated with BM development could influence screening and determine targeted treatment. We aimed to establish prevalence and incidence in these groups, stratified by genomic alterations.
METHODS
A systematic review and meta-analysis compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses were conducted (PROSPERO identification CRD42022315915). Articles published in MEDLINE, EMBASE, and Cochrane Library between January 2000 and May 2022 were included. Prevalence at diagnosis and incidence of new BM per year were obtained, including patients with EGFR, ALK, KRAS, and other alterations. Pooled incidence rates were calculated using random effects models.
RESULTS
A total of 64 unique articles were included (24,784 patients with NSCLC with prevalence data from 45 studies and 9058 patients with NSCLC having incidence data from 40 studies). Pooled BM prevalence at diagnosis was 28.6% (45 studies, 95% confidence interval [CI]: 26.1-31.0), and highest in patients that are ALK-positive (34.9%) or with RET-translocations (32.2%). With a median follow-up of 24 months, the per-year incidence of new BM was 0.13 in the wild-type group (14 studies, 95% CI: 0.11-0.16). Incidence was 0.16 in the EGFR group (16 studies, 95% CI: 0.11-0.21), 0.17 in the ALK group (five studies, 95% CI: 0.10-0.27), 0.10 in the KRAS group (four studies, 95% CI: 0.06-0.17), 0.13 in the ROS1 group (three studies, 95% CI: 0.06-0.28), and 0.12 in the RET group (two studies, 95% CI: 0.08-0.17).
CONCLUSIONS
Comprehensive meta-analysis indicates a higher prevalence and incidence of BM in patients with certain targetable genomic alterations. This supports brain imaging at staging and follow-up, and the need for targeted therapies with brain penetrance.
Topics: Humans; Lung Neoplasms; Incidence; Protein-Tyrosine Kinases; Proto-Oncogene Proteins p21(ras); Proto-Oncogene Proteins; Carcinoma, Non-Small-Cell Lung; Genomics; Brain Neoplasms; Receptor Protein-Tyrosine Kinases; ErbB Receptors
PubMed: 37392903
DOI: 10.1016/j.jtho.2023.06.017 -
BioMed Research International 2022Over the past ten years, the incidence rate of papillary thyroid carcinoma (PTC) worldwide has been increasing rapidly year by year, with the incidence rate increasing... (Review)
Review
BACKGROUND
Over the past ten years, the incidence rate of papillary thyroid carcinoma (PTC) worldwide has been increasing rapidly year by year, with the incidence rate increasing 6% annually. PTC has become the malignant tumor with the highest growth rate in the world that fourteen PTC-related mutant genes have been identified. Whether the BRAF mutation related to more aggressive clinicopathologic features and worse outcome in PTC remains variable and controversial. We aim to investigate the risk factors that may predict the BRAF mutation potential of these lesions and new prevention strategies in PTC patients.
METHODS
A total of 9,908 papillary thyroid carcinoma patients with average 74.6% BRAF mutations were analyzed (RevMan 5.3 software) in this study. The PubMed, Embase, and ISI Web of Science databases were systematically searched for works published through December 15, 2021.
RESULTS
The following variables were associated with an increased risk of BRAF mutation in PTC patients: age ≥ 45 years (OR = 1.39, 95%CI = 1.21-1.60, < 0.00001), male gender (OR = 1.13, 95%CI = 0.99-1.28, = 0.06), multifocality (OR = 1.22, 95%CI = 1.07-1.40, = 0.004), lymph node metastasis (OR = 1.33, 95%CI = 0.79-2.23, = 0.28), extrathyroidal extension + (OR = 1.61, 95%CI = 1.06-2.44, = 0.03), vascular invasion + (OR = 2.04, 95%CI = 1.32-3.15, = 0.001), and tumor node metastasis stage (OR = 1.61, 95%CI = 1.38-1.88, < 0.00001). In addition, tumor size (>1 cm) (OR = 0.51, 95%CI = 0.32-0.81, = 0.005) and distant metastasis (OR = 0.69, 95%CI = 0.22-2.21, = 0.54) had no association or risk with BRAF mutation in PTC patients.
CONCLUSION
Our systematic review identified the following significant risk factors of BRAF mutation in PTC patients: age (≥45 years), gender (male), multifocality, lymph node metastasis, vascular invasion, extrathyroidal extension, and advanced tumor node metastasis stage (stages III and IV). Tumor size (>1 cm) and distant metastasis do not appear to be correlated with BRAF mutation in PTC patients.
Topics: Carcinoma, Papillary; Humans; Lymphatic Metastasis; Male; Middle Aged; Mutation; Prognosis; Proto-Oncogene Proteins B-raf; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 35647194
DOI: 10.1155/2022/9959649 -
Journal of the National Cancer Institute Apr 2022KRAS and BRAF mutations are well-established predictive and prognostic factors in metastatic colorectal cancer; however, their impact in the adjuvant setting has not yet... (Meta-Analysis)
Meta-Analysis
BACKGROUND
KRAS and BRAF mutations are well-established predictive and prognostic factors in metastatic colorectal cancer; however, their impact in the adjuvant setting has not yet been established.
METHODS
We performed a meta-analysis of adjuvant phase III trials in patients with stage II and III colon cancer with available data on the impact of KRAS or BRAF mutations on both disease-free survival (DFS) and overall survival (OS). Trials were subgrouped based on whether adjustment for microsatellite instability (MSI) was performed and the subgroup effect was analyzed through a meta-regression. To increase the precision of the estimates, a joint DFS-OS (so-called "multivariate") meta-analysis was performed. All statistical tests were 2-sided.
RESULTS
Nine trials were selected (QUASAR 2, PETACC-8, N0147, CALGB-89803, NSABP-C07, NSABP-C08, PETACC-3, QUASAR, MOSAIC) including a total of 10 893 patients. In the primary meta-analysis, KRAS mutation was associated with poor DFS (pooled hazard ratio [HR] = 1.36, 95% confidence interval [CI] = 1.15 to 1.61, P < .001) and OS (pooled HR = 1.27, 95% CI = 1.03 to 1.55, P = .03) and BRAF mutation was also associated with poor DFS (pooled HR = 1.33, 95% CI = 1.00 to 1.78, P = .05) and OS (pooled HR = 1.49, 95% CI = 1.31 to 1.70, P < .001). The effect of the mutations on outcome was enhanced in the MSI-adjusted subgroup for both the KRAS mutation (pooled HR for DFS = 1.43, 95% CI = 1.15 to 1.79, P = .001; and pooled HR for OS = 1.33, 95% CI = 1.03 to 1.71, P = .03) and the BRAF mutation (pooled HR for DFS = 1.59, 95% CI = 1.22 to 2.07, P = .001; and pooled HR for OS = 1.67, 95% CI = 1.37 to 2.04, P < .001). The interaction between BRAF and MSI adjustment was statistically significant for DFS (Pinteraction = .02). This interaction was even more pronounced in the DFS-OS multivariate meta-analysis.
CONCLUSIONS
Both KRAS and BRAF mutations were statistically significantly associated with both DFS and OS, with the mutation effect being enhanced by MSI adjustment. Effective adjuvant treatment for microsatellite-stable BRAF or KRAS-mutated colon cancer represents an unmet clinical need, and exploring the use of recently available BRAF and KRAS inhibitors in this setting would be highly desirable.
Topics: Colonic Neoplasms; Colorectal Neoplasms; Humans; Male; Microsatellite Instability; Mutation; Neoplasm Staging; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Testicular Neoplasms
PubMed: 34542636
DOI: 10.1093/jnci/djab190 -
Redox Report : Communications in Free... Dec 2018p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative... (Review)
Review
BACKGROUND
p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis.
METHODS
A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases. Articles published in the English language between January 1, 1990 and March 1, 2017 were identified and isolated based on the analysis of p53 in skeletal muscle in both animal and cell culture models.
RESULTS
Literature was categorized according to the modality of imposed oxidative stress including exercise, diet modification, exogenous oxidizing agents, tissue manipulation, irradiation, and hypoxia. With low to moderate levels of oxidative stress, p53 is involved in activating pathways that increase time for cell repair, such as cell cycle arrest and autophagy, to enhance cell survival. However, with greater levels of stress intensity and duration, such as with irradiation, hypoxia, and oxidizing agents, the role of p53 switches to facilitate increased cellular stress levels by initiating DNA fragmentation to induce apoptosis, thereby preventing aberrant cell proliferation.
CONCLUSION
Current evidence confirms that p53 acts as a threshold regulator of cellular homeostasis. Therefore, within each modality, the intensity and duration are parameters of the oxidative stressor that must be analyzed to determine the role p53 plays in regulating signaling pathways to maintain cellular health and function in skeletal muscle.
ABBREVIATIONS
Acadl: acyl-CoA dehydrogenase, long chain; Acadm: acyl-CoA dehydrogenase, C-4 to C-12 straight chain; AIF: apoptosis-inducing factor; Akt: protein kinase B (PKB); AMPK: AMP-activated protein kinase; ATF-4: activating transcription factor 4; ATM: ATM serine/threonine kinase; Bax: BCL2 associated X, apoptosis regulator; Bcl-2: B cell Leukemia/Lymphoma 2 apoptosis regulator; Bhlhe40: basic helix-loop-helix family member e40; BH3: Borane; Bim: bcl-2 interacting mediator of cell death; Bok: Bcl-2 related ovarian killer; COX-IV: cytochrome c oxidase IV; cGMP: Cyclic guanosine monophosphate; c-myc: proto-oncogene protein; Cpt1b: carnitine palmitoyltransferase 1B; Dr5: death receptor 5; eNOS: endothelial nitric oxide synthase; ERK: extracellular regulated MAP kinase; Fas: Fas Cell surface death receptor; FDXR: Ferredoxin Reductase; FOXO3a: forkhead box O3; Gadd45a: growth arrest and DNA damage-inducible 45 alpha; GLS2: glutaminase 2; GLUT 1 and 4: glucose transporter 1(endothelial) and 4 (skeletal muscle); GSH: Glutathione; Hes1: hes family bHLH transcription factor 1; Hey1: hes related family bHLH transcription factor with YRPW motif 1; HIFI-α: hypoxia-inducible factor 1, α-subunit; HK2: Hexokinase 2; HSP70: Heat Shock Protein 70; HO: Hydrogen Peroxide; Id2: inhibitor of DNA-binding 2; IGF-1-BP3: Insulin-like growth factor binding protein 3; IL-1β: Interleukin 1 beta; iNOS: inducible nitric oxide synthase; IRS-1: Insulin receptor substrate 1; JNK: c-Jun N-terminal kinases; LY-83583: 6-anilino-5,8-quinolinedione; inhibitor of soluble guanylate cyclase and of cGMP production; Mdm 2/ 4: Mouse double minute 2 homolog (mouse) Mdm4 (humans); mtDNA: mitochondrial DNA; MURF1: Muscle RING-finger protein-1; MyoD: Myogenic differentiation 1; MyoG: myogenin; Nanog: Nanog homeobox; NF-kB: Nuclear factor-κB; NO: nitric oxide; NoxA: phorbol-12-myristate-13-acetate-induced protein 1 (Pmaip1); NRF-1: nuclear respiratory factor 1; Nrf2: Nuclear factor erythroid 2-related factor 2; P21: Cdkn1a cyclin-dependent kinase inhibitor 1A (P21); P38 MAPK: mitogen-activated protein kinases; p53R2: p53 inducible ribonucleotide reductase gene; P66Shc: src homology 2 domain-containing transforming protein C1; PERP: p53 apoptosis effector related to PMP-22; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PGM: phosphoglucomutase; PI3K: Phosphatidylinositol-4,5-bisphosphate 3-kinase; PKCβ: protein kinase c beta; PTEN: phosphatase and tensin homolog; PTIO: 2-phenyl-4, 4, 5, 5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) has been used as a nitric oxide (NO) scavenger; Puma: The p53 upregulated modulator of apoptosis; PW1: paternally expressed 3 (Peg3); RNS: Reactive nitrogen species; SIRT1: sirtuin 1; SCO2: cytochrome c oxidase assembly protein; SOD2: superoxide dismutase 2; Tfam: transcription factor A mitochondrial; TIGAR: Trp53 induced glycolysis repulatory phosphatase; TNF-a: tumor necrosis factor a; TRAF2: TNF receptor associated factor 2; TRAIL: type II transmembrane protein.
Topics: Animals; Diet; Exercise; Humans; Muscle, Skeletal; Oxidative Stress; Oxygen; Proto-Oncogene Mas; Radiation Injuries; Tumor Suppressor Protein p53
PubMed: 29298131
DOI: 10.1080/13510002.2017.1416773 -
European Journal of Cancer (Oxford,... Jul 2023Treatment options for advanced melanoma have increased with the US Food and Drug Administration approval of the anti-LAG3 plus anti-PD-1 relatlimab/nivolumab... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Treatment options for advanced melanoma have increased with the US Food and Drug Administration approval of the anti-LAG3 plus anti-PD-1 relatlimab/nivolumab combination. To date, ipilimumab/nivolumab is the benchmark of overall survival, despite a high toxicity profile. Furthermore, in BRAF-mutant patients, BRAF/MEK inhibitors and the atezolizumab/vemurafenib/cobimetinib triplet are also available treatments, making the first-line therapy selection more complex. To address this issue, we conducted a systematic review and network meta-analysis of the available first-line treatment options in advanced melanoma.
METHODS
Randomised clinical trials of previously untreated, advanced melanoma were included if at least one intervention arm contained a BRAF/MEK or an immune-checkpoint inhibitor (ICI). The aim was to indirectly compare the ICIs combinations ipilimumab/nivolumab and relatlimab/nivolumab, and these combinations with all the other first-line treatment options for advanced melanoma (irrespective of BRAF status) in terms of activity and safety. The coprimary end-points were progression-free survival (PFS), overall response rate (ORR) and grade ≥3 treatment-related adverse events (≥ G3 TRAEs) rate, defined according to Common Terminology Criteria for Adverse Events.
RESULTS
A total of 9070 metastatic melanoma patients treated in 18 randomised clinical trials were included in the network meta-analysis. No difference in PFS and ORR was observed between ipilimumab/nivolumab and relatlimab/nivolumab (HR = 0.99 [95% CI 0.75-1.31] and RR = 0.99 [95% CI 0.78-1.27], respectively). The PD-(L)1/BRAF/MEK inhibitors triplet combinations were superior to ipilimumab/nivolumab in terms of both PFS (HR = 0.56 [95% CI 0.37-0.84]) and ORR (RR = 3.07 [95% CI 1.61-5.85]). Ipilimumab/nivolumab showed the highest risk of developing ≥ G3 TRAEs. Relatlimab/nivolumab trended to a lower risk of ≥ G3 TRAEs (RR = 0.71 [95% CI 0.30-1.67]) versus ipilimumab/nivolumab.
CONCLUSION
Relatlimab/nivolumab showed similar PFS and ORR compared to ipilimumab/nivolumab, with a trend for a better safety profile.
Topics: Humans; Nivolumab; Ipilimumab; Network Meta-Analysis; Proto-Oncogene Proteins B-raf; Antineoplastic Combined Chemotherapy Protocols; Melanoma; Mitogen-Activated Protein Kinase Kinases
PubMed: 37196485
DOI: 10.1016/j.ejca.2023.04.010 -
Clinical Lung Cancer Sep 2023MET exon 14 (METex14) skipping is a rare oncogenic driver in non-small-cell lung cancer (NSCLC) for which targeted therapy with MET tyrosine kinase inhibitors (TKIs) was... (Review)
Review
INTRODUCTION
MET exon 14 (METex14) skipping is a rare oncogenic driver in non-small-cell lung cancer (NSCLC) for which targeted therapy with MET tyrosine kinase inhibitors (TKIs) was recently approved. Given the heterogeneity in published data of METex14 skipping NSCLC, we conducted a systematic literature review to evaluate its frequency, patient characteristics, and outcomes.
METHODS
On June 13, 2022 we conducted a systematic literature review of publications and conference abstracts reporting frequency, patient characteristics, or outcomes of patients with METex14 skipping NSCLC.
RESULTS
We included 139 studies reporting frequency or patient characteristics (350,997 patients), and 39 studies reporting clinical outcomes (3989 patients). Median METex14 skipping frequency was 2.0% in unselected patients with NSCLC, with minimal geographic variation. Median frequency was 2.4% in adenocarcinoma or nonsquamous subgroups, 12.0% in sarcomatoid, and 1.3% in squamous histology. Patients with METex14 skipping NSCLC were more likely to be elderly, have adenocarcinoma histology; there was no marked sex or smoking status distribution. In first line of treatment, median objective response rate ranged from 50.7% to 68.8% with targeted therapies (both values correspond to MET TKIs), was 33.3% with immunotherapy, and ranged from 23.1% to 27.0% with chemotherapy.
CONCLUSIONS
Patients with METex14 skipping are more likely to have certain characteristics, but no patient subgroup can be ruled out; thus, it is crucial to test all patients with NSCLC to identify suitable candidates for MET inhibitor therapy. MET TKIs appeared to result in higher efficacy outcomes, although no direct comparison with chemotherapy or immunotherapy regimens was found.
Topics: Aged; Humans; Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Exons; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met
PubMed: 37451931
DOI: 10.1016/j.cllc.2023.06.008 -
JCO Precision Oncology Aug 2022Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified... (Meta-Analysis)
Meta-Analysis
PURPOSE
Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified into three classes according to molecular characteristics. Consensus treatment strategies for class 2 and 3 BRAF mutations have not yet been established.
METHODS
We performed a systematic review and meta-analysis with published reports of individual patients with cancer harboring class 2 or 3 BRAF mutations from 2010 to 2021, to assess treatment outcomes with US Food and Drug Administration-approved mitogen-activated protein kinase (MAPK) pathway targeted therapy (MAPK TT) according to BRAF class, cancer type, and MAPK TT type. Coprimary outcomes were response rate and progression-free survival.
RESULTS
A total of 18,167 studies were screened, identifying 80 studies with 238 patients who met inclusion criteria. This included 167 patients with class 2 and 71 patients with class 3 BRAF mutations. Overall, 77 patients achieved a treatment response. In both univariate and multivariable analyses, response rate and progression-free survival were higher among patients with class 2 compared with class 3 mutations, findings that remain when analyses are restricted to patients with melanoma or lung primary cancers. MEK ± BRAF inhibitors demonstrated greater clinical activity in class 2 compared with class 3 BRAF-mutant tumors than BRAF or EGFR inhibitors.
CONCLUSION
This meta-analysis suggests that MAPK TTs have clinical activity in some class 2 and 3 BRAF-mutant cancers. BRAF class may dictate responsiveness to current and emerging treatment strategies, particularly in melanoma and lung cancers. Together, this analysis provides clinical validation of predictions made on the basis of a mutation classification system established in the preclinical literature. Further evaluation with prospective clinical trials is needed for this population.
Topics: Humans; Lung Neoplasms; Melanoma; Mitogen-Activated Protein Kinases; Prospective Studies; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; United States
PubMed: 35977349
DOI: 10.1200/PO.22.00107 -
Critical Reviews in Oncology/hematology Jan 2022This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cell-Free Nucleic Acids; DNA, Neoplasm; Humans; Mutation; Pancreatic Neoplasms; Prognosis; Proto-Oncogene Proteins p21(ras)
PubMed: 34843928
DOI: 10.1016/j.critrevonc.2021.103548 -
Cancers Nov 2022The discovery that ameloblastoma has a high mutation incidence of V600E may enable a better investigation of pathophysiology. However, there is inconsistent evidence... (Review)
Review
The discovery that ameloblastoma has a high mutation incidence of V600E may enable a better investigation of pathophysiology. However, there is inconsistent evidence regarding this mutation occurrence and its association with clinical information. This systematic review and meta-analysis aim to pool the overall mutation prevalence of V600E in reported ameloblastoma cases and to determine its association with patient demographic and clinicopathological features. Following the PRISMA guidelines, a comprehensive article search was conducted through four databases (Scopus, Google Scholar, PubMed, and Web of Science). Seventeen articles between 2014 and 2022 met the inclusion criteria with 833 ameloblastoma cases. For each included study, the significance of V600E on the outcome parameters was determined using odd ratios and 95% confidence intervals. Meta-analysis prevalence of V600E in ameloblastoma was 70.49%, and a significant meta-analysis association was reported for those younger than 54 years old and in the mandible. On the contrary, other factors, such as sex, histological variants, and recurrence, were insignificant. As a result of the significant outcome of V600E mutation in ameloblastoma pathogenesis, targeted therapy formulation can be developed with this handful of evidence.
PubMed: 36428683
DOI: 10.3390/cancers14225593