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Pigment Cell & Melanoma Research May 2022Acral melanoma (AM) tumors arise on the palms, soles, fingers, toes, and nailbeds. A comprehensive systematic meta-analysis of AM genomic aberrations has not been... (Meta-Analysis)
Meta-Analysis
Acral melanoma (AM) tumors arise on the palms, soles, fingers, toes, and nailbeds. A comprehensive systematic meta-analysis of AM genomic aberrations has not been conducted to date. A literature review was carried out to identify studies sequencing AM. Whole-genome/exome data from 181 samples were identified. Targeted panel sequencing data from MSK-IMPACT were included as a validation cohort (n = 92), and studies using targeted hot spot sequencing were also collated for BRAF (n = 26 studies), NRAS (n = 21), and KIT (n = 32). Statistical analysis indicated BRAF, NRAS, PTEN, TYRP1, and KIT as significantly mutated genes. Frequent copy-number aberrations were also found for important cancer genes, such as CDKN2A, KIT, MDM2, CCND1, CDK4, and PAK1, among others. Mapping genomic alterations within the context of the hallmarks of cancer identified four components frequently altered, including (i) sustained proliferative signaling and (ii) evading growth suppression, (iii) genome instability and mutation, and (iv) enabling replicative immortality. This analysis provides the largest analysis of genomic aberrations in AM in the literature to date and highlights pathways that may be therapeutically targetable.
Topics: Genomics; Humans; Melanoma; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35229492
DOI: 10.1111/pcmr.13034 -
JNCI Cancer Spectrum Jan 2024Colorectal cancer (CRC) is the second most common cause of cancer death globally. Recent clinical trials suggest an emerging role for HER2 as a potential clinically... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Colorectal cancer (CRC) is the second most common cause of cancer death globally. Recent clinical trials suggest an emerging role for HER2 as a potential clinically relevant biomarker in CRC. Testing for HER2 in CRC is not standard practice; consequently, the prevalence of HER2 positivity (HER2+) in patients with CRC remains uncertain.
METHODS
A systematic literature review and meta-analysis were conducted to generate estimates of proportions of patients with CRC with HER2 overexpression or HER2 amplification and HER2+ (either overexpression or amplification), overall and in patients with rat sarcoma virus (RAS) wild-type cancer. HER2+ was defined as 1) immunohistochemistry with a score of 3+, 2) immunohistochemistry with a score of 2+ and in situ hybridization+, or 3) next-generation sequencing positive.
RESULTS
Of 224 studies identified with information on HER2 in CRC, 52 studies used a US Food and Drug Administration-approved assay and were selected for further analysis. Estimated HER2+ rate was 4.1% (95% confidence interval [CI] = 3.4% to 5.0%) overall (n = 17 589). HER2+ rates were statistically higher in RAS wild-type (6.1%, 95% CI = 5.4% to 6.9%) vs RAS mutant CRC (1.1%, 95% CI = 0.3% to 4.4%; P < .0001). Despite limited clinical information, we confirmed enrichment of HER2+ CRC in patients with microsatellite stable and left-sided CRC.
CONCLUSION
This meta-analysis provides an estimate of HER2+ CRC and confirms enrichment of HER2 in microsatellite stable, left-sided, RAS wild-type CRC tumors. Our work is important given the recently described clinical efficacy of HER2-targeted therapies in HER2+ CRC and informs strategies for incorporation of HER2 testing into standard of care.
Topics: United States; Humans; Receptor, ErbB-2; Biomarkers, Tumor; Treatment Outcome; Immunohistochemistry; Colorectal Neoplasms
PubMed: 37815820
DOI: 10.1093/jncics/pkad082 -
In Vivo (Athens, Greece) 2022Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a rising incidence. There is a need for a non-invasive preoperative test to enable better... (Review)
Review
BACKGROUND/AIM
Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a rising incidence. There is a need for a non-invasive preoperative test to enable better patient counselling. The aim of this systematic review was to investigate the potential role of circulating microRNAs (miRNAs) in the diagnosis and prognosis of PTC.
MATERIALS AND METHODS
A systematic literature search was performed using MEDLINE, Cochrane, and Scopus databases (last search date was December 1, 2021). Studies investigating the expression of miRNAs in the serum or plasma of patients with PTC were deemed eligible for inclusion.
RESULTS
Among the 1,533 screened studies, 39 studies met the inclusion criteria. In total, 108 miRNAs candidates were identified in the serum, plasma, or exosomes of patients suffering from PTC. Furthermore, association of circulating miRNAs with thyroid cancer-specific clinicopathological features, such as tumor size (13 miRNAs), location (3 miRNAs), extrathyroidal extension (9 miRNAs), pre- vs. postoperative period (31 miRNAs), lymph node metastasis (17 miRNAs), TNM stage (9 miRNAs), BRAF V600E mutation (6 miRNAs), serum thyroglobulin levels (2 miRNAs), I avid metastases (13 miRNAs), and tumor recurrence (2 miRNAs) was also depicted in this study.
CONCLUSION
MiRNAs provide a potentially promising role in the diagnosis and prognosis of PTC. There is a correlation between miRNA expression profiles and specific clinicopathological features of PTC. However, to enable their use in clinical practice, further clinical studies are required to validate the predictive value and utility of miRNAs as biomarkers.
Topics: Carcinoma; Carcinoma, Papillary; Circulating MicroRNA; Humans; MicroRNAs; Mutation; Neoplasm Recurrence, Local; Prognosis; Proto-Oncogene Proteins B-raf; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 35738604
DOI: 10.21873/invivo.12866 -
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 -
BMC Cancer Apr 2021Over than one third (28-58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2)...
BACKGROUND
Over than one third (28-58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome.
METHODS
Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words "breast", "cancer", "trastuzumab" and "pregnancy". This study was performed in accordance with the PRISMA guidelines.
RESULTS
A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1-32). Oligohydramnios or anhydramnios was the most common (58.1%) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher's exact test). In 43.3% of cases a completely healthy neonate was born. 41.7% of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy.
CONCLUSIONS
Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.
Topics: Adult; Amniotic Fluid; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiotoxicity; Female; Fetus; Humans; Middle Aged; Oligohydramnios; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Trimesters; Receptor, ErbB-2; Time Factors; Trastuzumab; Young Adult
PubMed: 33902516
DOI: 10.1186/s12885-021-08162-3 -
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 -
Lung Cancer (Amsterdam, Netherlands) Jul 2021Increased thromboembolism (TE) has been reported in ALK+ and ROS1+ non-small cell lung cancer (NSCLC). (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Increased thromboembolism (TE) has been reported in ALK+ and ROS1+ non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
Odds ratios (OR) and hazard ratios (HR) of TE were calculated from meta-analysis and time-to-event analysis respectively for either ALK+ or ROS1+ NSCLC patients.
RESULTS
We identified eight studies (766 ALK+, 143 ROS1+, 2314 non-ALK+ and non-ROS1+ NSCLC patients) for the meta-analysis. For ALK+ NSCLC, the pooled OR was 2.00 (95% CI: 1.60-2.50) for total TE (TTE) by random-effects model, 2.10 (95% CI: 1.70-2.60) for venous thromboembolism (VTE), and 1.24 (95% CI: 0.80-1.91) for arterial thromboembolism (ATE). For ROS1+ NSCLC, the pooled OR was 3.08 (95% CI: 1.95-4.86) for TTE, and 3.15 (95% CI: 1.83-5.43) for VTE. Six studies (739 ALK+, 137 ROS1+, 561 EGFR+, 714 "wildtype" NSCLC patients) were included in the time-to-event analysis. The TTE incidence rate was 17.4 (95% CI: 15.3-19.5) per 100 pateint-years for ALK+ NSCLC, and 32.1 (95% CI: 24.6-39.6) per 100 patient-years for ROS1+ NSCLC with a 50 % cumulative incidence rate at year 3 of diagnosis. HR for TTE was 2.35 (95% CI: 1.90-2.92, p < 0.001) and 3.23 (95% CI: 2.40-4.34, p < 0.001) for ALK+ and ROS1+ NSCLC, respectively. Comparing ROS1+ NSCLC to ALK+ NSCLC, HR for TTE was 1.37 (95% CI: 1.05-1.79, p = 0.020).
CONCLUSIONS
ALK+ and ROS1+ NSCLC patients had an increased risk of TE. ROS1+ NSCLC had further increased risk of TE over ALK+ NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; Gene Rearrangement; Humans; Lung Neoplasms; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases
PubMed: 34049720
DOI: 10.1016/j.lungcan.2021.05.019 -
International Journal of Molecular... Jun 2023Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) characterized by a hallmark translocation of t (11; 14). CD10 negativity has been used to... (Meta-Analysis)
Meta-Analysis Review
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma (NHL) characterized by a hallmark translocation of t (11; 14). CD10 negativity has been used to differentiate MCL from other NHL types; however, recently, there has been an increase in the number of reported cases of CD10-positive MCL. This warrants further investigation into this rarer immunophenotype and its clinical significance. BCL6, which is a master transcription factor for the regulation of cell proliferation and key oncogene in B cell lymphomagenesis, has been reported to have co-expression with CD10 in MCL. The clinical significance of this aberrant antigen expression remains unknown. We conducted a systematic review by searching four databases and selected five retrospective analyses and five case series. Two survival analyses were conducted to determine if BCL6 positivity conferred a survival difference: 1. BCL6+ vs. BCL6- MCL. 2. BCL6+/CD10+ vs. BCL6-/CD10+ MCL. Correlation analysis was conducted to determine if BCL6 positivity correlated with the Ki67 proliferation index (PI). Overall survival (OS) rates were performed by the Kaplan-Meier method and log-rank test. Our analyses revealed that BCL6+ MCL had significantly shorter overall survival (median OS: 14 months vs. 43 months; = 0.01), BCL6+/CD10+ MCL had an inferior outcome vs. BCL6+/CD10- MCL (median OS: 20 months vs. 55 months = 0.1828), BCL6+ MCL had significantly higher percentages of Ki67% (Ki67% difference: 24.29; = 0.0094), and BCL6 positivity had a positive correlation with CD10+ status with an odds ratio 5.11 (2.49, 10.46; = 0.0000286). Our analysis showed that BCL6 expression is correlated with CD10 positivity in MCL, and BCL6 expression demonstrated an inferior overall survival. The higher Ki67 PI in BCL6+ MCL compared to BCL6- MCL further supports the idea that the BCL6+ immunophenotype may have prognostic value in MCL. MCL management should consider incorporating prognostic scoring systems adjusted for BCL6 expression. Targeted therapies against BCL6 may offer potential therapeutic options for managing MCL with aberrant immunophenotypes.
Topics: Humans; Adult; Lymphoma, Mantle-Cell; Neprilysin; Proto-Oncogene Proteins c-bcl-6; Retrospective Studies; Prognosis; Ki-67 Antigen
PubMed: 37373354
DOI: 10.3390/ijms241210207 -
ESMO Open Feb 2024Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of T-DXd in the human epidermal growth factor receptor 2 (HER2)-positive BCBM population.
PATIENTS AND METHODS
We searched PubMed, Embase, and Cochrane Library databases as well as American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and San Antonio Breast Cancer Symposium (SABCS) websites for clinical trials (CTs) and observational studies evaluating T-DXd in patients with HER2-positive BCBM. Heterogeneity was assessed with I statistics. Random effects models were used for all statistical analyses, which were carried out using R software (version 4.2.2).
RESULTS
Ten studies were included, six CTs (n = 189) and four observational studies (n = 130), with a total of 319 patients. The median progression-free survival was 15 months [95% confidence interval (CI) 13.9-16.1 months]. The objective response rate (ORR) was 61% (95% CI 52% to 70%), and the intracranial (IC)-ORR was 61% (95% CI 54% to 69%). No significant differences in ORR and IC-ORR were observed between CTs and observational studies (P = 0.31 and 0.58, respectively). The clinical benefit rate (CBR) was 80% (95% CI 52% to 94%), and the IC-CBR was 70% (95% CI 54% to 82%). The ORR was 68% (95% CI 57% to 77%) in the subgroup of patients with stable BMs and 60% (95% CI 48%-72%) in patients with active BM, with no significant difference between groups (P = 0.35).
CONCLUSIONS
Our systematic review and meta-analysis supports the IC activity of T-DXd in patients with stable BM and active BM.
TRIAL REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42023422589.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Brain Neoplasms; Camptothecin; Receptor, ErbB-2; Immunoconjugates
PubMed: 38320430
DOI: 10.1016/j.esmoop.2024.102233