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World Journal of Clinical Oncology Aug 2016To evaluate the current role of sorafenib, an oral multikinase inhibitor in the treatment of breast cancer.
AIM
To evaluate the current role of sorafenib, an oral multikinase inhibitor in the treatment of breast cancer.
METHODS
An extensive search of the literature until March 2016 was carried out in Medline and clinicaltrials.gov, by using the search terms "sorafenib" and "breast cancer". Papers found were checked for further relevant publications. Overall, 21 relevant studies were found, 18 in advanced breast cancer (16 in stage IV and two in stages III-IV) and three in early breast cancer.
RESULTS
Among studies in advanced breast cancer, there were two trials with sorafenib as monotherapy, four trials of sorafenib in combination with taxanes, two in combination with capecitabine, one with gemcitabine and/or capecitabine, one with vinorelbine, one with bevacizumab, one with pemetrexed and one with ixabepilone, three trials of sorafenib in combination with endocrine therapy and two trials in women with brain metastases undergoing whole brain radiotherapy. In addition, there was one trial of sorafenib added to standard chemotherapy in the adjuvant setting, and two trials in the neoadjuvant setting. In general, sorafenib was well tolerated in breast cancer patients, though its dosage had to be adjusted in some trials, and discontinuation rates were high, particularly for the combination of sorafenib with anastrozole. Sorafenib monotherapy and combinations with taxanes, bevacizumab and ixabepilone showed inadequate efficacy, while efficacy results from combinations with gemcitabine and/or capecitabine and possibly tamoxifen were more promising.
CONCLUSION
At present, sorafenib should not be used for the treatment of breast cancer outside of clinical trials and more clinical data are needed in order to support its standard use in breast cancer therapy.
PubMed: 27579253
DOI: 10.5306/wjco.v7.i4.331 -
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 -
Clinical Kidney Journal Apr 2016Advanced melanoma has been traditionally unresponsive to standard chemotherapy agents and used to have a dismal prognosis. Genetically targeted small-molecule inhibitors... (Review)
Review
Advanced melanoma has been traditionally unresponsive to standard chemotherapy agents and used to have a dismal prognosis. Genetically targeted small-molecule inhibitors of the oncogenic BRAF V600 mutation or a downstream signaling partner (MEK mitogen-activated protein kinase) are effective treatment options for the 40-50% of melanomas that harbor mutations in BRAF. Selective BRAF and MEK inhibitors induce frequent and dramatic objective responses and markedly improve survival compared with cytotoxic chemotherapy. In the past decade after discovery of this mutation, drugs such as vemurafenib and dabrafenib have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency for the treatment of V600-mutated melanomas. While the initial trials did not signal any renal toxicities with the BRAF inhibitors, recent case reports, case series and FDA adverse reporting systems have uncovered significant nephrotoxicities with these agents. In this article, we systematically review the nephrotoxicities of these agents. Based on recently published data, it appears that there are lower rates of kidney disease and cutaneous lesions seen with dabrafenib compared with vemurafenib. The pathology reported in the few kidney biopsies done so far are suggestive of tubulo interstitial damage with an acute and chronic component. Electrolyte disorders such as hypokalemia, hyponatremia and hypophosphatemia have been reported as well. Routine monitoring of serum creatinine and electrolytes and calculation of glomerular filtration rate prior to the first administration when treating with dabrafenib and vemurafenib are essential.
PubMed: 26985376
DOI: 10.1093/ckj/sfv149 -
Journal of Global Oncology Dec 2015We conducted a literature-based meta-analysis of the risk of cardiovascular toxicities associated with MEK inhibitors. (Review)
Review
PURPOSE
We conducted a literature-based meta-analysis of the risk of cardiovascular toxicities associated with MEK inhibitors.
METHODS
Eligible trials included randomized phase II and III trials of patients with cancer who were given a mitogen activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (trametinib, selumetinib, or cobimetinib) and that described events of hypertension and decreased ejection fraction.
RESULTS
Our search strategy yielded 300 potentially relevant citations from PubMed/MEDLINE, Google Scholar, and Cochrane Central Register of Controlled Trials. After ineligible studies were excluded, a total of 10 clinical trials were considered eligible for the meta-analysis. The relative risk for all grades of hypertension was 1.54 (95% CI, 1.02 to 2.32; = .05), 1.85 (95% CI, 1.01 to 3.40; = .05) for high-grade hypertension, and 4.92 (95% CI, 2.93 to 8.25; < .001) for decreased ejection fraction. Subgroup analysis revealed no difference between trametinib and selumetinib for risk of hypertension.
CONCLUSION
Our meta-analysis demonstrated that MEK inhibitor-based treatment is associated with an increased risk of all-grade and high-grade hypertension and asymptomatic decrease in ejection fraction. Clinicians should be aware of this risk and perform regular assessment.
PubMed: 28804776
DOI: 10.1200/JGO.2015.000802 -
Breast Cancer Research : BCR Aug 2015Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk. The aim of this study was to review the postulated association... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk. The aim of this study was to review the postulated association between insulin and insulin analogue treatment and breast cancer development, and plausible mechanisms.
METHOD
A systematic literature search was performed on breast cell-line, animal and human studies using the key words 'insulin analogue' and 'breast neoplasia' in MEDLINE at PubMed, EMBASE, and ISI Web of Science databases. A quantitative and qualitative review was performed on the epidemiological data; due to a limited number of reported estimates, a meta-analysis was performed for glargine only. A comprehensive overview was composed for in vitro and animal studies. Protein and gene expression was analysed for the cell lines most frequently used in the included in vitro studies.
RESULTS
In total 16 in vitro, 5 animal, 2 in vivo human and 29 epidemiological papers were included. Insulin AspB10 showed mitogenic properties in vitro and in animal studies. Glargine was the only clinically available insulin analogue for which an increased proliferative potential was found in breast cancer cell lines. However, the pooled analysis of 13 epidemiological studies did not show evidence for an association between insulin glargine treatment and an increased breast cancer risk (HR 1.04; 95 % CI 0.91-1.17; p=0.49) versus no glargine in patients with diabetes mellitus. It has to be taken into account that the number of animal studies was limited, and epidemiological studies were underpowered and suffered from methodological limitations.
CONCLUSION
There is no compelling evidence that any clinically available insulin analogue (Aspart, Determir, Glargine, Glulisine or Lispro), nor human insulin increases breast cancer risk. Overall, the data suggests that insulin treatment is not involved in breast tumour initiation, but might induce breast tumour progression by up regulating mitogenic signalling pathways.
Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin Glargine; MCF-7 Cells; Risk
PubMed: 26242987
DOI: 10.1186/s13058-015-0611-2