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Acta Oncologica (Stockholm, Sweden) Feb 2018advanced-stage non-small cell lung cancer (NSCLC) is characterized by having limited treatment options and thus a poor prognosis. However, new treatment options, in the... (Review)
Review
BACKGROUND
advanced-stage non-small cell lung cancer (NSCLC) is characterized by having limited treatment options and thus a poor prognosis. However, new treatment options, in the form of targeted agents (TA), have emerged during recent years. This systematic review aims to provide an overview of the accessible literature in PubMed evaluating TA used on NSCLC patients, and the resulting survival outcomes.
METHOD
this systematic literature review was conducted by reviewing all relevant literature in PubMed. Six separate searches were performed: Three searches where controlled entry terms were used and three free text searches. Furthermore, other relevant publications were included manually. A total of seventy-two studies met the search criteria and were thus further analyzed and evaluated.
RESULTS
In the included studies, various TAs and their effect on different molecular targets have been evaluated. Clinical responses vary considerably among the different genetic aberrations. The majority of studies evaluated TA for epidermal growth factor receptor (EGFR) mutations and TA for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements. Studies regarding the use of TA for Rat sarcoma (RAS), rapidly accelerated fibrosarcoma (RAF), ROS proto-oncogene 1 (ROS1) rearrangement, Receptor tyrosine-protein kinase erbB-2 (ERBB2), Phosphatidylinositol 3-kinase (PIK3CA)/v-akt murine thymoma viral oncogene homolog; protein kinase B(AKT)/Phosphatase and tensin homolog deleted on chromosome 10(PTEN), The mammalian target of rapamycin (mTOR), and Mesenchymal-epithelial transition factor (MET) were included as well. In general, studies comparing treatment outcomes in EGFR-mutated patients and EML4-ALK (ALK) rearranged patients after use of either TA or standard chemotherapy, present significant better results after TA.
CONCLUSIONS
This systematic review provides an overview of available literature in PubMed regarding NSCLC and TA. Included studies point toward that TA appears to be a promising therapeutic tool in treating NSCLC patients and use of TA is expected to result in improved treatment outcomes.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Molecular Targeted Therapy; Proto-Oncogene Mas
PubMed: 29172833
DOI: 10.1080/0284186X.2017.1404634 -
European Review For Medical and... Aug 2017Lung cancer is the leading cause of cancer-related mortality. Over 80% of all lung cancer cases are non-small-cell lung cancer (NSCLC) and approximately 5% of NSCLC... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Lung cancer is the leading cause of cancer-related mortality. Over 80% of all lung cancer cases are non-small-cell lung cancer (NSCLC) and approximately 5% of NSCLC patients are positive for anaplastic lymphoma kinase (ALK) gene rearrangement or fusion with echinoderm microtubule-associated protein-like 4 (EML4). NSCLC patients with positive ALK-EML4 gene fusion are highly sensitive to ALK-inhibitors. While the efficacy of the ALK-inhibitors in the treatment of NSCLC has been consistently reported, a limited number of randomized, large-scale clinical trials have been reported. The current study was, therefore, designed to systematically review and appraise current knowledge and conduct a meta-analysis on phase I, II, and III clinical trials in which ALK-inhibitors were used to treat NSCLC.
MATERIALS AND METHODS
The PubMed online database was thoroughly searched. A total of 26 articles were included in a qualitative systematic review, and four of them were used to conduct the quantitative meta-analysis.
RESULTS
We found that ALK inhibitors significantly improved the overall survival (OS) and progress free survival (PFS) of NSCLC patients, especially of ALK or ROS1 gene fusion-positive cases. ALK inhibitors contributed to better therapeutic outcomes regarding increased one-year and two-year OS, PFS, and ORR (Odds ratio: 4.393, 95% CI: 3.302-5.845, p < 0.001). Visual disturbance was the most common side effect observed in the patients treated with crizotinib, whereas mild gastrointestinal reactions, such as diarrhea and nausea, were most frequent in the patients treated with the 2nd generation of ALK inhibitors.
CONCLUSIONS
ALK inhibitors are safe and effective in the treatment of NSCLC patients, especially those with positive ALK-EML4 gene fusion or rearrangement.
Topics: Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Crizotinib; Humans; Lung Neoplasms; Pyrazoles; Pyridines; Randomized Controlled Trials as Topic; Receptor Protein-Tyrosine Kinases
PubMed: 28829490
DOI: No ID Found -
Journal of Neurotrauma Jul 2017This systematic review examined the association between genetics and risk for sustaining a traumatic brain injury. We retrieved articles published in English from 1980... (Review)
Review
This systematic review examined the association between genetics and risk for sustaining a traumatic brain injury. We retrieved articles published in English from 1980 to July 2016 obtained from the online databases PubMed, PsycINFO, MEDLINE, Embase, and Web of Science. In total 5903 articles were identified, 77 underwent full-text screening, and 6 were included in this review. Five studies examined the risk of concussion associated with apolipoprotein E alleles (APOE-ɛ2, ɛ3,ɛ4), and polymorphisms of the APOE promoter (rs405509), brain derived neurotrophic factor (BDNF, rs6265), and dopamine receptor D2 (DRD2, rs1800497) were each considered in two studies. Microtubule associated protein tau (TAU exon 6 polymorphisms His47Tyr [rs2258689] and Ser53Pro [rs10445337]), and neurofilament heavy (NEHF, rs165602) genotypic variants, were the focus of single studies. No study showed an increased risk associated solely with the presence of the APOE-ɛ4 allele, nor were there any significant findings for the NEFH, TAU, or DRD2 genotypic variants. Two studies examined the APOE promoter -219G/T polymorphism in athletes, and both found an association with concussion. Both BDNF studies also found a significant association with concussion incidence; United States soldiers with the Met/Met genotype were more likely to report a history of concussion prior to deployment and to sustain a concussion during deployment. We conclude that the APOE promoter -219G/T polymorphism and the BDNF Met/Met genotype might confer risk for sustaining a TBI. Based on research to date, the APOE-ɛ4 allele does not appear to influence risk. More research is needed to determine if these findings replicate.
Topics: Alleles; Apolipoproteins E; Brain Concussion; Brain-Derived Neurotrophic Factor; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Genetic; Receptors, Dopamine D2; Risk Factors
PubMed: 28100103
DOI: 10.1089/neu.2016.4833 -
Critical Reviews in Oncology/hematology Jan 2017Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease... (Review)
Review
BACKGROUND
Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL.
OBJECTIVE
Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30 malignancies in humans.
DATA SOURCES
We searched various databases including PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015).
ELIGIBILITY CRITERIA
Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered.
INCLUDED STUDIES
A total of 28 articles met these criteria and are summarized in this manuscript.
CONCLUSION
Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30 malignancies.
Topics: Antineoplastic Agents; Brentuximab Vedotin; Clinical Trials, Phase II as Topic; Humans; Immunoconjugates; Lymphoma, Non-Hodgkin; Neoplasm Recurrence, Local; Prospective Studies
PubMed: 28010897
DOI: 10.1016/j.critrevonc.2016.11.009 -
Oxidative Medicine and Cellular... 2016Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia... (Review)
Review
Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.
Topics: Animals; Antineoplastic Agents; Drugs, Chinese Herbal; Humans; Hydrophobic and Hydrophilic Interactions; Neoplasms; Reactive Oxygen Species; Salvia miltiorrhiza
PubMed: 27579153
DOI: 10.1155/2016/5293284 -
Acta Pharmaceutica Sinica. B Nov 2015Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for... (Review)
Review
Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for enzyme inhibitors, notably caspases, calpains, and cathepsins. The reactive, active-site cysteine provides specificity for many inhibitor designs over other families of proteases, such as aspartate and serine; however, a) inhibitor strategies often use covalent enzyme modification, and b) obtaining selectivity within families of cysteine proteases and their isozymes is problematic. This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders; the latter focus providing an interesting query for the contemporary assumptions that irreversible, covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.
PubMed: 26713267
DOI: 10.1016/j.apsb.2015.08.001 -
Clinical Breast Cancer Apr 2016Agents that target microtubule (MT) dynamics have been used extensively for the treatment of metastatic breast cancer (MBC). Among these agents are taxanes... (Review)
Review
Agents that target microtubule (MT) dynamics have been used extensively for the treatment of metastatic breast cancer (MBC). Among these agents are taxanes (solvent-based paclitaxel [sb-paclitaxel], docetaxel, and nab-paclitaxel) and non-taxanes, such as eribulin and ixabepilone. Although these agents have been approved for the treatment of MBC, questions regarding the ideal agent, regimen (single agent vs. combination vs. sequential), and schedule still remain. This systematic review examined pivotal trials for taxanes, eribulin, and ixabepilone as well as first-line taxane trials in MBC. Only randomized trials that enrolled ≥ 100 patients were included. Publications on combination regimens with targeted agents were excluded unless they also included a comparison between nontargeted regimens. The studies were grouped into taxane versus taxane, sb-paclitaxel versus non-taxane, and docetaxel versus non-taxane regimens. In taxane versus taxane comparisons, the efficacy of sb-paclitaxel and docetaxel appeared similar, nab-paclitaxel every 3 weeks (q3w) appeared superior to sb-paclitaxel q3w, and weekly nab-paclitaxel appeared superior to docetaxel. In general, taxane regimens demonstrated higher overall response rates (ORRs) versus non-taxane regimens; however, only 2 trials demonstrated longer overall survival (OS) for taxane regimens. Taxanes will likely continue to be used in earlier lines of therapy, whereas eribulin and ixabepilone may be more appropriate for later lines of treatment. Ongoing research may identify biomarkers that could help in selecting the appropriate MT-targeted agent for a given patient.
Topics: Breast Neoplasms; Female; Humans; Taxoids
PubMed: 26603443
DOI: 10.1016/j.clbc.2015.09.007 -
Cancer Treatment Reviews Dec 2015Taxanes, including paclitaxel and docetaxel, are indispensable for treatment of cancer. Development of toxicity frequently necessitates dose reduction or discontinuation... (Review)
Review
BACKGROUND
Taxanes, including paclitaxel and docetaxel, are indispensable for treatment of cancer. Development of toxicity frequently necessitates dose reduction or discontinuation of therapy, despite clinical response.
OBJECTIVE
Pharmacogenetic studies were reviewed for identification of genetic variants possibly underlying individual susceptibility to adverse events.
METHOD
We conducted a systematic search in Pubmed and Embase for pharmacogenetic reports with focus on commonly reported taxane-related gastrointestinal, hematological and neurological toxicities in adult patients with solid tumors. The findings from a total of 51 eligible studies are presented in a comprehensive way.
RESULTS
Most frequently investigated single nucleotide polymorphisms (SNPs) were located in genes encoding proteins affecting pharmacokinetics, such as drug transporters and genes of the cytochrome P450 family. Inconclusive data for risk of toxicity as well as for effects on drug exposure were reported on variants in ABCB1, CYP3A4, CYP3A5 and, for paclitaxel, CYP2C8. Interest is also dedicated towards genes involved in pharmacodynamics, such as detoxification of reactive oxygen species, DNA repair, neuronal processes and microtubule function. Recent studies include variants in TUBB2A, EPHA5 and EPHA6 for a possible association with neurotoxicity. Variations in methodological approach, sample size, study design, treatment schedule and end-point of toxicity affect consistency of results.
CONCLUSION
This review illustrates the complexity to well design pharmacogenetic studies for validation of SNPs that may clarify differences in taxane-induced toxicities among individuals. Novel genes encoding cellular targets of taxanes deserve further analysis by means of robust patient cohorts and definition of objective end-points.
Topics: ATP Binding Cassette Transporter, Subfamily B; Antineoplastic Agents; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP3A; Docetaxel; Gastrointestinal Diseases; Hematologic Diseases; Humans; Neurotoxicity Syndromes; Paclitaxel; Pharmacogenetics; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptor, EphA5; Receptor, EphA6; Taxoids; Tubulin
PubMed: 26585358
DOI: 10.1016/j.ctrv.2015.10.010 -
OncoTargets and Therapy 2015Ovarian cancer is the most lethal gynecologic malignancy; consequently, there is a need for effective therapies. Epothilones are microtubule-stabilizing agents that...
Ovarian cancer is the most lethal gynecologic malignancy; consequently, there is a need for effective therapies. Epothilones are microtubule-stabilizing agents that inhibit cell growth. Currently, patupilone and its four synthetic derivatives ixabepilone, BMS-310705, sagopilone, 20-desmethyl-20-methylsulfanyl epothilone B and epothilone D, as well as its derivative KOS-1584, are under clinical evaluation. This is the first systematic review conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines that synthesizes all available data emerging from trials and evaluates the efficacy and safety of epothilones in epithelial ovarian, primary fallopian tube, and primary peritoneal cancer. Despite the fact that epothilones have proven active in taxane-resistant settings in preclinical models, it is not yet clear from Phase II/III studies reviewed here that their clinical activity is superior to that of taxanes. Nevertheless, responses to epothilones have been observed in platinum-refractory/resistant ovarian cancer patients. Moreover, despite the shared mechanism of action of epothilones, their clinical profile seems clearly different, with diarrhea being the most common dose-limiting toxicity encountered with patupilone, whereas neutropenia and sensory neuropathy are the most common toxic effects observed with the other epothilones. In any case, randomized trials comparing epothilones with standard treatments seem warranted to define further the role of these agents, whereas biomarker analysis might further optimize patient selection.
PubMed: 26316786
DOI: 10.2147/OTT.S77342 -
Tumour Biology : the Journal of the... Aug 2014Use of the autophagy-related markers beclin-1 (BECN1) and microtubule-associated protein light chain 3B (LC3B) as prognostic markers has been extensively investigated in... (Meta-Analysis)
Meta-Analysis Review
Use of the autophagy-related markers beclin-1 (BECN1) and microtubule-associated protein light chain 3B (LC3B) as prognostic markers has been extensively investigated in various kinds of cancers. However, their prognostic roles are still controversial and not firmly validated. We systematically reviewed the evidence from various studies concerning the relationship between BECN1 and LC3B expression in cancers and overall survival (OS)/disease-free survival (DFS) to elucidate this issue. PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched in July 2013 (then updated in April 2014) to identify eligible cohort studies that reported associations between BECN1 or LC3B expression and OS/DFS in cancer patients. Combined hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were pooled using fixed-effects or random-effects models according to heterogeneity in different groups. A total of 23 studies in distinct cancers were eligible for systematic review and meta-analysis. Our pooled results identified that a high expression of BECN1 is associated with favorable OS in gastric cancer (HR = 0.49, 95 % CI = 0.34-0.72) and lymphoma (HR = 0.25, 95 % CI = 0.11-0.57), whereas a high expression of LC3B predicts adverse OS in breast cancer (HR = 1.98, 95 % CI = 1.25-3.13). This systematic review and meta-analysis indicated that the autophagy-related marker BECN1 might be a predictive factor of favorable prognosis in gastric cancer, breast cancer, and lymphoma and LC3B might predict unfavorable prognosis of breast cancer. Nevertheless, due to the limited number and retrospective design of the original studies, more powerful prospective cohorts are required to verify these conclusions.
Topics: Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Disease-Free Survival; Humans; Membrane Proteins; Microtubule-Associated Proteins; Neoplasms; Prognosis
PubMed: 24838948
DOI: 10.1007/s13277-014-2060-4