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Recent Patents on Anti-cancer Drug... 2017Heat shock proteins (Hsp) are major chaperone molecules that have recently emerged as cancer therapeutic targets owing to their involvement in tumor cell proliferation,... (Review)
Review
BACKGROUND
Heat shock proteins (Hsp) are major chaperone molecules that have recently emerged as cancer therapeutic targets owing to their involvement in tumor cell proliferation, differentiation, invasion and metastasis. High levels of extracellular Hsp90 and Hsp70 have been closely associated with a wide range of human cancers. Accumulating evidence suggests that the pharmacological inhibition of these molecules can play a pivotal role in non-surgical cancer treatment. Efforts have been taken to develop monoclonal antibodies (mAbs) and antibody fragments targeting extracellular Hsp90 and Hsp70, alone or conjugated with standard anticancer agents, to control several types of cancer, such as breast, colon, prostate or melanoma.
OBJECTIVE
To provide an overview on the development of monoclonal antibodies and antibody fragments with capacity to bind Hsp90 and Hsp70, aiming at being used for cancer treatment.
METHODS
A systematic review was performed using European Patent Office and Google patents databases.
RESULTS
Based on the available literature and patents, we report the potential anticancer strategies based on these biological molecules.
CONCLUSIONS
Supported by the recent developments in this field, Hsp targeting antibodies therapy may emerge for clinical use in the future for cancer patients, namely as antibody-drug conjugates combining the specificity of these antibodies with the potency of cytotoxic drugs.
Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents; Drug Delivery Systems; Heat-Shock Proteins; Humans; Neoplasms; Patents as Topic
PubMed: 27881057
DOI: 10.2174/1574892812666161123141516 -
PharmacoEconomics Sep 2014This systematic literature review aimed to evaluate and summarize the existing evidence on resource use and costs associated with the diagnosis and treatment of head and... (Review)
Review
BACKGROUND
This systematic literature review aimed to evaluate and summarize the existing evidence on resource use and costs associated with the diagnosis and treatment of head and neck cancer (HNC) in adult patients, to better understand the currently available data. The costs associated with HNC are complex, as the disease involves multiple sites, and treatment may require a multidisciplinary medical team and different treatment modalities.
METHODS
Databases (MEDLINE and Embase) were searched to identify studies published in English between October 2003 and October 2013 analyzing the economics of HNC in adult patients. Additional relevant publications were identified through manual searches of abstracts from recent conference proceedings.
RESULTS
Of 606 studies initially identified, 77 met the inclusion criteria and were evaluated in the assessment. Most included studies were conducted in the USA. The vast majority of studies assessed direct costs of HNC, such as those associated with diagnosis and screening, radiotherapy, chemotherapy, surgery, side effects of treatment, and follow-up care. The costs of treatment far exceeded those for other aspects of care. There was considerable heterogeneity in the reporting of economic outcomes in the included studies; truly comparable cost data were sparse in the literature. Based on these limited data, in the US costs associated with systemic therapy were greater than costs for surgery or radiotherapy. However, this trend was not seen in Europe, where surgery incurred a higher cost than radiotherapy with or without chemotherapy.
CONCLUSIONS
Most studies investigating the direct healthcare costs of HNC have utilized US databases of claims to public and private payers. Data from these studies suggested that costs generally are higher for HNC patients with recurrent and/or metastatic disease, for patients undergoing surgery, and for those patients insured by private payers. Further work is needed, particularly in Europe and other regions outside the USA; prospective studies assessing the cost associated with HNC would allow for more systematic comparison of costs, and would provide valuable economic information to payers, providers, and patients.
Topics: Antineoplastic Agents; Asia; Brazil; Cost of Illness; Costs and Cost Analysis; Europe; Head and Neck Neoplasms; Health Care Costs; Humans; Palliative Care; Positron-Emission Tomography; Telemedicine; Terminal Care; United States
PubMed: 24842794
DOI: 10.1007/s40273-014-0169-3 -
Expert Review of Pharmacoeconomics &... Jun 2018The Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) has been used to evaluate the clinical benefits and risks of oncology treatments. However, limited... (Review)
Review
INTRODUCTION
The Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) has been used to evaluate the clinical benefits and risks of oncology treatments. However, limited information is available to interpret and contextualize Q-TWiST results.
AREAS COVERED
A systematic review of Q-TWiST literature was conducted to provide contextualizing benchmarks for future studies. 51 articles with 81 unique Q-TWiST comparisons were identified. The mean (95% CI) and median absolute Q-TWiST gains for treatment versus control arms were 2.78 (1.82-3.73) months and 2.20 months across all cancers, respectively. The mean (median) relative Q-TWiST gains were 7.8% (7.2%) across all cancers. Most (88%) studies reported positive gains. The percentage of studies with relative Q-TWiST gains ≥10% (ie, clinically important difference) and ≥15% (ie, clearly clinically important difference) were 40.0% and 22.7%, respectively
EXPERT COMMENTARY
The relevance of Q-TWiST in assessing net clinical benefits of cancer therapy has not diminished, despite an arguably low number of published studies. The interest in such assessment is highlighted by the recent emergence of oncology value frameworks. The Q-TWiST should be compelling to clinicians as it integrates clinical information (ie, toxicity, relapse/progression, and survival) and patient preferences for each of these states into a single meaningful index.
Topics: Antineoplastic Agents; Benchmarking; Disease Progression; Humans; Neoplasms; Patient Preference; Quality-Adjusted Life Years; Survival Rate; Time Factors
PubMed: 29402128
DOI: 10.1080/14737167.2018.1434414 -
Expert Opinion on Investigational Drugs Jun 2016Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor... (Review)
Review
INTRODUCTION
Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor (VEGF). Since the Ras/Raf/MEK/ERK pathway is implicated in the proliferation of multiple myeloma (MM) cells and VEGF in bone marrow neovascularization, sorafenib is a drug offering the potential for targeting two important pathogenetic mechanisms involved in MM. Thus, sorafenib is being proposed for use in MM.
AREAS COVERED
In this review, the authors discuss the rationale for the use of sorafenib in MM. They then summarize the clinical development of sorafenib in MM, from initial Phase I to Phase II studies. A systematic literature review of the trials was performed using PubMed.
EXPERT OPINION
Preliminary data from phase I/II trials showed that sorafenib had a good safety profile but minimal anti-myeloma activity as a single agent in relapsed/refractory patients. Results of phase II trials, evaluating sorafenib combined with new drugs, such as bortezomib and lenalidomide are eagerly awaited.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Cell Proliferation; Humans; Lenalidomide; Multiple Myeloma; Niacinamide; Phenylurea Compounds; Protein Kinase Inhibitors; Sorafenib; Thalidomide
PubMed: 26998658
DOI: 10.1517/13543784.2016.1169272 -
Advanced Drug Delivery Reviews 2020Controlled nano-systems for drug delivery are designed to deliver therapeutical drugs to desirable sites on demand. Due to the diverse physiological functions of...
Controlled nano-systems for drug delivery are designed to deliver therapeutical drugs to desirable sites on demand. Due to the diverse physiological functions of peptides, it is reasonable to introduce peptides into anti-tumor nano-system. The integration of peptides into nanomaterials has complementary advantages, which not only avoids the rapid degradation of peptides in vivo, but also improves the intelligence and functionality of the nano-system. We summarized the functional peptides with targeting and stimulus-responsive properties, and the present review outlined the most relevant and recent developed peptide-based multifunctional nanomaterials for tumor therapy.
Topics: Animals; Antineoplastic Agents; Drug Delivery Systems; Humans; Immunotherapy; Nanoparticles; Neoplasms; Neovascularization, Pathologic; Peptides
PubMed: 33080257
DOI: 10.1016/j.addr.2020.10.009 -
Anticancer Research Sep 2021Adverse event (AE) frequencies observed in interventional clinical trials are difficult to interpret when the placebo control is missing.
BACKGROUND/AIM
Adverse event (AE) frequencies observed in interventional clinical trials are difficult to interpret when the placebo control is missing.
MATERIALS AND METHODS
Systematic literature review of AEs reported from the placebo arms of randomized cancer trials between 2008 and 2021. Imputation of missing values assuming normal distribution of hemoglobin values.
RESULTS
Anemia grade 1 or higher was reported in 46 of 100 placebo monotherapy cohorts with a mean frequency of 23.4% (SD=27%) of the enrolled patients. The reported frequency depended on the type of cancer; other demographic variables had no significant influence on anemia frequency.
CONCLUSION
External controls for anemia in clinical trials should be disease specific.
Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Agents; Child; Female; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Young Adult
PubMed: 34475081
DOI: 10.21873/anticanres.15266 -
Journal of Cosmetic Dermatology Feb 2022Several treatments have been used to reduce inflammation and to reverse epithelial alterations in actinic cheilitis (AC).
INTRODUCTION
Several treatments have been used to reduce inflammation and to reverse epithelial alterations in actinic cheilitis (AC).
AIM
A systematic review was conducted to analyze the potential of topical treatments for remission and clinical improvement of AC as well as patient acceptability.
METHODS
A systematic review of clinical trials was conducted following the PICO strategy to answer the following question: Are topical anti-inflammatory and antineoplastic agents effective in the treatment of actinic cheilitis? The quality of the studies was assessed by ROB-2, and the certainty of evidence was rated by GRADE guidelines.
RESULTS
Eight clinical trials were selected, including four that investigated the use of anti-inflammatory drugs and four use of antineoplastic agents. The use of 3% diclofenac sodium was associated with partial remission of AC, while 5% imiquimod and ingenol mebutate promoted complete remission. Furthermore, 5% fluorouracil was the drug most associated with complications during treatment. Diclofenac sodium (3%) and fludroxycortide showed the best acceptance by the patients, especially in terms of symptom relief and comfort provided.
CONCLUSION
The anti-inflammatory and antineoplastic agents analyzed largely provided good clinical outcomes, with evidence of remission of AC lesions, development of few local adverse reactions during treatment, and good patient adherence.
Topics: Aged; Anti-Inflammatory Agents; Antineoplastic Agents; Cheilitis; Humans; Treatment Outcome
PubMed: 33786961
DOI: 10.1111/jocd.14118 -
Expert Opinion on Drug Safety Oct 2015We performed a systematic review and meta-analysis of the risk of oral and gastrointestinal (GI) mucosal injury associated with ramucirumab. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We performed a systematic review and meta-analysis of the risk of oral and gastrointestinal (GI) mucosal injury associated with ramucirumab.
PATIENTS AND METHODS
Eligible studies included randomized Phase II and III trials of patients with solid tumors on ramucirumab: describing events of stomatitis, diarrhea, GI perforation and GI hemorrhage.
RESULTS
Our search strategy yielded 167 potentially relevant citations from Pubmed/Medline, CENTRAL Cochrane registry, European society of medical oncology meeting abstracts and American Society of Clinical Oncology meeting library. After exclusion of ineligible studies, a total of 11 clinical trials were considered eligible for the meta-analysis. The RR of all-grade stomatitis, diarrhea, GI perforation and GI hemorrhage were 1.62 (95% CI 1.31 - 2.00; p < 0.00001), 1.15 (95% CI 1.07 - 1.24; p < 0.0001), 3.29 (95% CI 1.54 - 7.04; p = 0.002) and 1.92 (95% CI 1.03 - 3.57; p = 0.04), respectively. The RR of high-grade stomatitis, diarrhea, GI perforation and GI hemorrhage were 2.72 (95% CI 1.76 - 4.19; p < 0.00001), 1.28 (95% CI 0.96 - 1.71; p = 0.09), 3.37 (95% CI 1.51 - 7.54; p = 0.03) and 1.26 (95% CI 0.79 - 2.01; p = 0.34), respectively.
CONCLUSIONS
Our meta-analysis has demonstrated that ramucirumab-based combination treatment is associated with an increased risk of high-grade stomatitis and GI perforation compared to control treatment.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Gastrointestinal Diseases; Humans; Neoplasms; Randomized Controlled Trials as Topic; Ramucirumab
PubMed: 26313327
DOI: 10.1517/14740338.2015.1074677 -
World Neurosurgery Oct 2023Sonodynamic therapy (SDT) has emerged as an encouraging noninvasive technique that uses ultrasound to activate targeted agents to induce antitumor effects for the... (Review)
Review
Sonodynamic therapy (SDT) has emerged as an encouraging noninvasive technique that uses ultrasound to activate targeted agents to induce antitumor effects for the treatment of glioma. With extensive variation in the types of sonosensitizers, protocols for sonication, and model systems, a comprehensive overview of existing preclinical data on the efficacy of SDT in glioma treatment is warranted. Here, we conduct a systematic review of preclinical and early clinical literature on implementing SDT to treat in vitro and in vivo models of glioma. Our findings suggest that coupling sonosensitizers such as 5-aminolevulinic acid, hematoporphyrin monomethyl ether, and sinoporphyrin sodium with focused ultrasound induces robust cytotoxic activity in tumor cells (in vitro and in vivo). These effects are likely mediated by the oxidative stress induced by reactive oxygen species production, apoptotic signaling cascades, and intracellular calcium overload. Future research is needed to better understand the biochemical and mechanistic properties of SDT, and ongoing trials may help elucidate the clinical feasibility of glioma treatment with optimized sonically activated treatments.
Topics: Humans; Ultrasonic Therapy; Glioma; Aminolevulinic Acid; Apoptosis; Reactive Oxygen Species; Antineoplastic Agents; Cell Line, Tumor
PubMed: 37454909
DOI: 10.1016/j.wneu.2023.07.030 -
Phytomedicine : International Journal... Feb 2023Natural products have long been regarded as a source of anticancer compounds with low toxicity. Evidence revealed that maslinic acid (MA), a widely distributed... (Review)
Review
BACKGROUND
Natural products have long been regarded as a source of anticancer compounds with low toxicity. Evidence revealed that maslinic acid (MA), a widely distributed pentacyclic triterpene in common foodstuffs, exhibited pronounced inhibitory effects against various cancer cell lines. Most cancer cells thrive by acquiring cancer hallmarks, as coined by Hanahan and Weinberg in 2000 and 2011.
PURPOSE
This represents the first systematic review concerning the anticancer properties of MA as these cancer hallmarks are targeted. It aims to summarize the antineoplastic activities of MA, discuss the diverse mechanisms of action based on the effects of MA exerted on each hallmark.
METHODS
A comprehensive literature search was conducted using the search terms "maslinic," "cancer," "tumor," and "neoplasm," to retrieve articles from the databases MEDLINE, EMBASE, Web of Science, and Scopus published up to September 2022. Study selection was conducted by three reviewers independently from title and abstract screening until full-text evaluation. Data extraction was done by one reviewer and counterchecked by the second reviewer.
RESULTS
Of the 330 articles assessed, 40 papers met the inclusion criteria and revealed that MA inhibited 16 different cancer cell types. MA impacted every cancer hallmark by targeting multiple pathways.
CONCLUSION
This review provides insights regarding the inhibitory effects of MA against various cancers and its remarkable biological properties as a pleiotropic bioactive compound, which encourage further investigations.
Topics: Humans; Antineoplastic Agents; Neoplasms; Oleanolic Acid; Triterpenes
PubMed: 36621168
DOI: 10.1016/j.phymed.2022.154631