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The Breast Journal 2023Third-generation aromatase inhibitors (AIs) are the mainstay of treatment in hormone receptor (HR)-positive breast cancer. Even though it is considered to be a... (Review)
Review
BACKGROUND
Third-generation aromatase inhibitors (AIs) are the mainstay of treatment in hormone receptor (HR)-positive breast cancer. Even though it is considered to be a well-tolerated therapy, AI-induced musculoskeletal symptoms are common and may be accused for treatment discontinuation. Recently, selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors changed the therapeutic setting, and currently, ribociclib, palbociclib, and abemaciclib are all approved in combination with nonsteroidal AIs in patients with ER-positive, HER2-negative advanced or metastatic breast cancer. This systematic review aims to identify the frequency of aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) in the adjuvant setting in patients under AI monotherapy compared to patients under combination therapy with AIs and CDK4/6 inhibitors and demonstrate the underlying mechanism of action.
METHODS
This study was performed in accordance with PRISMA guidelines. The literature search and data extraction from all randomized clinical trials (RCTs) were done by two independent investigators. Eligible articles were identified by a search of MEDLINE and ClinicalTrial.gov database concerning the period 2000/01/01-2021/05/01.
RESULTS
Arthralgia was reported in 13.2 to 68.7% of patients receiving AIs for early-stage breast cancer, while arthralgia induced by CDK4/6 inhibitors occurred in a much lower rate [20.5-41.2%]. Bone pain (5-28.7% vs. 2.2-17.2%), back pain (2-13.4% vs. 8-11.2%), and arthritis (3.6-33.6% vs. 0.32%) were reported less frequently in patients receiving the combination of CDK4/6 inhibitors with ET.
CONCLUSIONS
CDK4/6 inhibitors might have a protective effect against joint inflammation and arthralgia occurrence. Further studies are warranted to investigate arthralgia incidence in this population.
Topics: Humans; Female; Aromatase Inhibitors; Breast Neoplasms; Arthralgia; Cyclin-Dependent Kinase 4
PubMed: 37293258
DOI: 10.1155/2023/3614296 -
Asian Pacific Journal of Cancer... Mar 2023Cholangiocarcinoma (CCA) is the second most frequent hepatobiliary cancer after hepatocellular carcinoma with a poor prognosis and limited treatment options. This study...
BACKGROUND
Cholangiocarcinoma (CCA) is the second most frequent hepatobiliary cancer after hepatocellular carcinoma with a poor prognosis and limited treatment options. This study aimed to review existing knowledge on the genetic basis of CCA, molecular targets/signaling pathways involved in the pathogenesis, disease progression and prognosis, including potential targets for targeted therapies of CCA.
METHODS
The systematic review was performed in compliance with PRISMA guidelines. A systematic search in PubMed and Science Direct databases was performed using the following keywords: "cholangiocarcinoma", AND "molecular target" AND/OR "signaling pathway", AND/OR "targeted therapy", AND/OR "cancer chemotherapy." The eligibility criteria included: i) full-text articles published in English, ii) articles with in vitro and/or in vivo and/or clinical studies of molecular targets/signaling pathwanys related to CCA pathogenesis/disease progression/prognosis and/or targeted therapy. Seventy-three studies that fulfilled the eligibility criteria were finally included in the final data synthesis.
RESULTS
A total of 833 relevant articles published up to April 2022 were identified and 73 sttudies that fulfilled the eligibility criteria were finally included in the analysis. The molecular biomarkers and drugs targeting signalling pathways were reported. Recent research has been focused on targeting the apoptotic and cell proliferation pathways, and in addition, the angiogenesis and metastasis pathway. More effort focused on testing the efficacy of combination therapies against the cancer cell and specifically CCA. The PI3K (Phosphoinositide 3-kinases)/ERK/Akt (AKT serine/threonine kinase 1)/mTOR (mammalian target of rapamycin) signaling pathway and HER2 (Human epidermal growth factor receptor 2) and EGFR (Epidermal Growth Factor Receptor) pathways are the most potential targets for CCA therapy.
CONCLUSION
The information obtained could be exploited for further development of diagnostic tools for early diagnosis of CCA, as well as effective CCA-targeted therapies.
Topics: Humans; Proto-Oncogene Proteins c-akt; Signal Transduction; Cholangiocarcinoma; Cell Proliferation; Phosphatidylinositol 3-Kinases; Bile Ducts, Intrahepatic; Bile Duct Neoplasms; Disease Progression; Cell Line, Tumor
PubMed: 36974526
DOI: 10.31557/APJCP.2023.24.3.741 -
Medicine Jan 2022To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma.
METHODS
A systematic review and meta-analysis was designed. We visited PubMed, Embase, China National Knowledge Infrastructure Database, Database of Chinese sci-tech periodicals, WanFang Database, and China Biology Medicine disc to search for Chinese and English publications of prospective studies and retrospective studies investigating the association of EGFR/p-EGFR and nasopharyngeal carcinoma prognosis from inception to April 2021. The inclusion criteria were that the samples should be pathologically confirmed as nasopharyngeal carcinoma and the expression of EGFR/p-EGFR should be detected via immunohistochemistry; the study should analyze the prognostic significance of EGFR/p-EGFR in nasopharyngeal carcinoma; hazard ratio (HR) and 95% confidence interval (CI) should be reported in the study or could be derived from survival curves; and the outcomes of the study should include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).
RESULTS
A total of 18 studies evaluating 1451 samples were included. For studies that reported OS as an outcome, EGFR overexpression indicated worse OS of nasopharyngeal carcinoma patients. The heterogeneity between studies was high (I2 = 91%, P < .01), and a random-effect model was used to combine the effect size (HR = 1.71, 95% CI [1.21, 2.41], P < .01). Further sensitivity analysis and prespecified subgroup analysis were performed to detect the source of heterogeneity, and the results showed that the heterogeneity could not be eliminated. Publication bias assessed by funnel plots and Begg test and Egger test was low (Begg test: P = .846 and Egger test: P = .074). p-EGFR was not correlated with the OS of nasopharyngeal carcinoma patients (HR = 1.01, 95% CI [0.88, 1.15], P = .92). For studies that reported DFS, EGFR overexpression was associated with worse DFS in patients with nasopharyngeal carcinoma (HR = 2.53, 95% CI [1.84, 3.47], P < .01). For studies that reported PFS, EGFR overexpression was not correlated with the PFS of nasopharyngeal carcinoma patients (HR = 1.86, 95% CI [0.90, 3.82], P = .09). For studies that reported DMFS, EGFR overexpression was not correlated with the DMFS of nasopharyngeal carcinoma patients, and high heterogeneity between studies was detected (I2 = 97%, P < .01). A random-effect model was used to combine the effect size (HR = 1.80, 95% CI [0.56, 5.76], P = .32). A sensitivity analysis was conducted. Publication bias was detected to be low (Begg test: P = .817 and Egger test: P = .954). There was no correlation between p-EGFR overexpression and DMFS in patients with nasopharyngeal carcinoma (HR = 1.20, 95% CI [0.95, 1.52], P = .12).
CONCLUSION
In nasopharyngeal carcinoma patients, EGFR overexpression could be used as a biomarker that predicts poor OS and DFS, but not a prognostic biomarker for PFS and DMFS. The overexpression of p-EGFR was not shown to be associated with the prognosis of nasopharyngeal carcinoma patients and could not be used as a prognostic biomarker.
ETHICS AND DISSEMINATION
This study was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), and reported as stated by the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Neither ethical approval nor informed consent was required since this study was conducted based on previous publications.
INPLASY REGISTRATION NUMBER
INPLASY 202150010.
Topics: ErbB Receptors; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis
PubMed: 35060503
DOI: 10.1097/MD.0000000000028507 -
Breast (Edinburgh, Scotland) Oct 2023Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed the first-line treatment for metastatic disease with increased rates of treatment response, overall survival (OS), and progression-free survival (PFS). We performed a pooled analysis of randomized trials to validate or refute the hypothesis that there is a significant survival benefit of adding anti-CDK4/6 inhibitors to standard endocrine therapy (ET) in older patients with advanced BC.
METHODS
We selected only English-language phase II/III randomized controlled trials that compared ET alone with ET with anti-CDK4/6 inhibitors in the treatment of advanced BC, with subgroups reporting the outcomes of elderly patients (usually at least 65 years). The primary endpoint was OS.
RESULTS
The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials. The addition of CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced mortality risk by 20% in younger patients (fixed-effect model; HR 0.80; 95% CI 0.72-0.9; p < 0.01) and 21% in older BC patients (HR 0.79; 95% CI 0.69-0.91; p < 0.01). No OS data were available for patients ≥70 years.
CONCLUSION
This large, pooled analysis is the first to demonstrate that CDK4/6 inhibitors confer OS and PFS benefits in elderly patients (those aged ≥65 years) with advanced ER + BC and to indicate that it should be discussed with and offered to all patients after geriatric assessment and according to the toxicity profile.
Topics: Aged; Humans; Female; Breast Neoplasms; Cyclin-Dependent Kinase 4; Receptor, ErbB-2; Cyclin-Dependent Kinase 6; Fulvestrant; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37198053
DOI: 10.1016/j.breast.2023.05.002 -
PloS One 2017One of the critical mechanisms of gastrointestinal cancer pathogenesis is the silencing of death associated protein kinase 1 (DAPK1), which could be caused by aberrant... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
One of the critical mechanisms of gastrointestinal cancer pathogenesis is the silencing of death associated protein kinase 1 (DAPK1), which could be caused by aberrant methylation of the promoter. However, the relationship between DAPK1 methylation and the risk of gastrointestinal cancer is still controversial. Hence, we conducted this study to determine the potential correlation.
METHODS
Eligible publications were searched in the Pubmed, Embase, and Cochrane Library through November 2016 according to the inclusion criteria and exclusion criteria. Revman 5.3 and Stata 12.0 software were used to analyze the relevant data regarding the association between the frequency of DAPK1 methylation and gastrointestinal cancer.
RESULTS
A total of 22 studies with 2406 patients were included in this meta analysis. Methylation of DAPK1 was positively related with the risk of gastrointestinal cancer (odds ratio [OR] = 5.35, 95% confidence interval [CI]: 2.76-10.38, P<0.00001, random effects model). The source of heterogeneity was analyzed by sensitivity analysis and subgroup analysis. After omitting one heterogeneous study, the I2 decreased and the OR increased in pooled analysis. Also, the heterogeneity decreased most significantly in the subgroup of studies that had a sample size of less than 60 cases. Then, the correlations between DAPK1 methylation and clinicopathological features of gastrointestinal cancer were assessed. DAPK1 methylation was positively correlated with the lymph node (N) stage (positive vs. negative, OR = 1.45, 95%CI: 1.01-2.06, P = 0.04, fixed effects model) and poor differentiation (OR = 1.55, 95%CI: 1.02-2.35, P = 0.04, fixed effects model) in gastric cancer, and the association was significant among Asian patients. However, among cases of gastrointestinal cancer, the association between DAPK1 methylation and tumor (T) stage, N stage, distant metastasis (M) stage, and cancer differentiation were not statistically significant.
CONCLUSIONS
DAPK1 methylation is a potential biomarker for the early diagnosis of gastrointestinal cancer. Further analysis of the clinicopathological features indicated that aberrant methylation of DAPK1 is positively associated with the tumorigenesis of gastrointestinal cancer, and metastasis of gastric cancer.
Topics: DNA Methylation; Death-Associated Protein Kinases; Gastrointestinal Neoplasms; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Risk Factors
PubMed: 28934284
DOI: 10.1371/journal.pone.0184959 -
Acta Ophthalmologica Mar 2023Intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) agents are first-line treatment for neovascular age-related macular degeneration (nAMD).... (Review)
Review
Intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) agents are first-line treatment for neovascular age-related macular degeneration (nAMD). Phase 3 trials demonstrated non-inferiority of anti-VEGF therapy with brolucizumab compared with aflibercept in best corrected visual acuity (BCVA) gains, with superior anatomical outcomes after brolucizumab. The purpose of the review was to summarize real-world efficacy and safety data on brolucizumab in patients with nAMD. The review protocol was registered with PROSPERO (ID: CRD42021290530). We conducted systematic searches in Embase, Medline and key ophthalmology congress websites (19 October 2021). Original reports of efficacy and/or safety in patients receiving brolucizumab to treat nAMD in clinical practice were eligible. The descriptive summary includes reports describing at least 10 brolucizumab-treated eyes. In total, 2907 brolucizumab-treated eyes from 26 studies were included. Outcomes were available for treatment-naive eyes (six studies), eyes switched to brolucizumab from other anti-VEGFs (16 studies), and/or treatment-naive and switch eyes combined (eight studies). Follow-up time points ranged from 4 weeks to 1 year post-brolucizumab initiation. For BCVA, significant improvements compared with brolucizumab initiation were reported in four of six studies in treatment-naive eyes (mean BCVA improvement, range: +3.7 to +11.9 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and in three of 12 studies in switch eyes (range: +9.0 to +15 ETDRS letters) (all p < 0.05); remaining studies reported no significant post-brolucizumab BCVA changes. For central subfield thickness (CST), improvements post-brolucizumab initiation were reported in all six studies in treatment-naive eyes (mean CST improvement, range: -113.4 to -150.1 μm) and in eight of 11 studies in switch eyes (range: -26 to -185.7 μm) (all p < 0.05). The 14 studies reporting on intraretinal, subretinal and/or total fluid observed improvements post-brolucizumab initiation. The four studies comparing treatment intervals observed extension of the interval between injections after switching to brolucizumab from other anti-VEGFs. Incidence of intraocular inflammation ranged from 0% to 19%. In conclusion, real-world efficacy and safety data concur with brolucizumab pivotal trials. Additionally, reduction of disease activity in anti-VEGF switch eyes was demonstrated by fluid reduction and/or visual acuity gain, along with prolongation of the interval between injections.
Topics: Humans; Ranibizumab; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Intravitreal Injections; Macular Degeneration; Receptors, Vascular Endothelial Growth Factor; Diabetic Retinopathy; Recombinant Fusion Proteins; Wet Macular Degeneration
PubMed: 36117281
DOI: 10.1111/aos.15242 -
Indian Journal of Dental Research :... 2022Ameloblastoma is a benign, locally aggressive neoplasm that needs extensive surgical resection. The goal of this article is to obtain an in-depth review of benign... (Review)
Review
Ameloblastoma is a benign, locally aggressive neoplasm that needs extensive surgical resection. The goal of this article is to obtain an in-depth review of benign ameloblastomas to determine the available level of evidence and the possible benefit of targeted therapeutics for the treatment of ameloblastoma and BRAF V600E mutation in ameloblastoma. An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, EBSCO, and Web of Science for eligible studies published between 1975 and 2021. The systematic review is registered with INPLASY (INPLASY202260018). The review included 2 case series and 17 case reports. The histopathological type, anatomic location, expression of BRAF mutation, additional mutations, and molecular-targeted therapies of the 19 reviewed articles were summarized and tabulated. Interestingly, the majority of the primary site of ameloblastoma was located in the mandible (80.9%) compared to the maxilla (17%). The tumour size was reported in nine of the included studies. Most of the included studies in the review exhibited ameloblastoma with BRAF V600E mutations and responded to molecular-targeted therapies. Molecular therapies employing BRAF and/or MEK inhibitors in ameloblastoma with BRAF V600E mutations proved to be an appropriate treatment based on the limited available evidence. It is essential further to deepen our understanding at the clinical and molecular level to enhance the precision of management of ameloblastoma.
Topics: Humans; Ameloblastoma; Molecular Targeted Therapy; Mutation; Proto-Oncogene Proteins B-raf
PubMed: 36656197
DOI: 10.4103/ijdr.ijdr_456_22 -
Systematic Reviews Dec 2022Trastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Trastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from lapatinib and lapatinib plus trastuzumab therapy than standard trastuzumab therapy. This study presents an update of a systematic review and meta-analysis involving comparison of lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy.
AIM
We determined whether trastuzumab plus lapatinib or lapatinib therapy is not inferior to trastuzumab therapy in HER2-positive breast cancer patients.
METHODS
Relevant trials were searched in CNKI, Wanfang, VIP, Sinomed, PubMed, Embase, and Cochrane CENTRAL databases from inception until October 25, 2021. Primary outcomes were OS, DFS/EFS, and PFS while secondary outcomes were pCR (ypT0/is ypN0), pCR (ypT0/is ypN0/+), ORR, DCR, rate of BCS, RFS, cardiac toxicities, and other toxicities.
RESULTS
Thirteen randomized controlled trials were included in this study. Trastuzumab combined with lapatinib therapy was found to be superior to standard trastuzumab therapy alone with regard to overall survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0), pathologic complete response (ypT0/is ypN0/+), recurrence-free survival, higher incidences of diarrhea, and rash/skin toxicity. Lapatinib therapy was established to be inferior to trastuzumab therapy in overall survival, progression-free survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0) and pathologic complete response (ypT0/is ypN0/+), diarrhea, and rash/skin toxicity and had a low incidence of left ventricular ejection fraction decline.
CONCLUSIONS
The efficacy of trastuzumab combined with lapatinib therapy is superior to standard trastuzumab therapy alone; however, it has more non-cardiac grade III/IV toxicities. Moreover, the efficacy of lapatinib therapy is inferior to that of standard trastuzumab therapy alone.
Topics: Humans; Female; Trastuzumab; Lapatinib; Breast Neoplasms; Receptor, ErbB-2; Stroke Volume; Antineoplastic Combined Chemotherapy Protocols; Ventricular Function, Left; Randomized Controlled Trials as Topic
PubMed: 36496473
DOI: 10.1186/s13643-022-02134-9 -
Archives of Gynecology and Obstetrics Jun 2021The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated (POLE-mt), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), p53-wild-type (p53-wt). These groups might have different pathogenesis and risk factors, and might occur in different phenotypes of patients. However, these data are still lacking.
OBJECTIVE
To provide a clinical characterization of the ProMisE groups of EC.
METHODS
A systematic review and meta-analysis was performed by searching seven electronic databases from their inception to December 2020, for all studies reporting clinical characteristics of EC patients in each ProMisE group. Pooled means of age and BMI and pooled prevalence of FIGO stage I and adjuvant treatment in each ProMisE group were calculated.
RESULTS
Six studies with 1, 879 women were included in the systematic review. Pooled means (with standard error) and prevalence values were: in the MMR-d group, age = 66.5 ± 0.6; BMI = 30.6 ± 1.2; stage I = 72.6%; adjuvant treatment = 47.3%; in the POLE-mt group, age = 58.6 ± 2.7; BMI = 27.2 ± 0.9; stage I = 93.7%; adjuvant treatment = 53.6%; in the p53-wt group, age = 64.2 ± 1.9; BMI = 32.3 ± 1.4; stage I = 80.5%; adjuvant treatment = 45.3%; in the p53-abn group, age = 71.1 ± 0.5; BMI = 29.1 ± 0.5; stage I = 50.8%; adjuvant treatment = 64.4%.
CONCLUSION
The ProMisE groups identify different phenotypes of patients. The POLE-mt group included the youngest women, with the lower BMI and the highest prevalence of stage I. The p53-wt group included patients with the highest BMI. The p53-abn group included the oldest women, with the highest prevalence of adjuvant treatment and the lowest prevalence of stage I. The MMR-d group showed intermediate values among the ProMisE groups for all clinical features.
Topics: Aged; Biomarkers, Tumor; DNA Polymerase II; Endometrial Neoplasms; Female; Genes, p53; Humans; Middle Aged; Mutation; PTEN Phosphohydrolase; Phenotype; Poly-ADP-Ribose Binding Proteins; Prognosis; Risk Assessment; Tumor Suppressor Protein p53
PubMed: 33754186
DOI: 10.1007/s00404-021-06028-4 -
Cancer Metastasis Reviews Mar 2022Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine... (Review)
Review
BACKGROUND
Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine kinases (RTKs) in this pathology remains poorly clarified. Here, we provide a systematic analysis of the RTK superfamily in the context of neuroblastoma pathogenesis.
METHODS
Statistical correlations for all RTK family members' expression to neuroblastoma patient survival across 10 independent patient cohorts were annotated, synthesized, and ranked using the R2: Genomics Analysis and Visualization Platform. Gene expression of selected members across different cancer cell lines was further analyzed in the Cancer Cell Line Encyclopedia, part of the Cancer Dependency Map portal (depmap portal ( http://depmap.org )). Finally, we provide a detailed literature review for highly ranked candidates.
RESULTS
Our analysis defined two subsets of RTKs showing robust associations with either better or worse survival, constituting potential novel players in neuroblastoma pathophysiology, diagnosis, and therapy. We review the available literature regarding the oncogenic functions of these RTKs, their roles in neuroblastoma pathophysiology, and potential utility as therapeutic targets.
CONCLUSIONS
Our systematic analysis and review of the RTK superfamily in neuroblastoma pathogenesis provides a new resource to guide the research community towards focused efforts investigating signaling pathways that contribute to neuroblastoma tumor establishment, growth, and/or aggressiveness and targeting these druggable molecules in novel therapeutic strategies.
Topics: Carcinogenesis; Cell Line, Tumor; Child; Humans; Neuroblastoma; Receptor Protein-Tyrosine Kinases; Signal Transduction
PubMed: 34716856
DOI: 10.1007/s10555-021-10001-7