Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. Based on successful randomized phase III trials, anti-EGFR and anti-VEGF therapeutics have entered clinical practice. Cetuximab (Erbitux), an EGFR-specific antibody, is currently approved in the United States in combination with irinotecan (Camptosar) for patients with metastatic colorectal cancer refractory to irinotecan or as a single agent for patients unable to tolerate irinotecan-based therapy. In retrospective analyses, patients with EGFR-expressing rectal cancer undergoing neoadjuvant radiation therapy had a significantly inferior disease-free survival and lower rates of achieving pathologic complete response. Based on the positive data in metastatic colorectal cancer and synergy with radiation therapy seen in preclinical models, there is a strong rationale to combine cetuximab with neoadjuvant radiation therapy and chemotherapy in rectal cancer. Bevacizumab (Avastin), a VEGF-specific antibody, was the first antiangiogenic agent to be approved in the United States for use in combination with standard chemotherapy in the first- and second-line of treatment in metastatic colorectal cancer. VEGF-targeted therapy may lead to indirect killing of cancer cells by damaging tumor blood vessels, and may increase the radiosensitivity of tumor-associated endothelial cells. VEGF blockade can also "normalize" tumor vasculature, thereby leading to greater tumor oxygenation and drug penetration. This review will address completed and ongoing trials that have established and continue to clarify the effects of these agents in rectal cancer.
 ...
PMID:Targeted therapy in rectal cancer. 1791 Mar 11

Background: Tyrosine kinase inhibitors (TKIs) are standard treatment options for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Increasing clinical investigations have explored the value of EGFR-TKIs plus antiangiogenic drugs as the first-line treatment for EGFR-mutated NSCLC. Methods: We systematically searched PubMed, Cochrane Library, and EMBASE for randomized controlled trials (RCTs) investigating EGFR-TKIs administered with or without antiangiogenic agents for advanced EGFR-mutated NSCLC. The latest RCT that was presented orally at the 2019 European Society for Medical Oncology Congress was obtained online. The endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rates (DCRs), and grade 3 or higher adverse events (AEs). Results: We included seven articles on five trials with 1,226 patients. The interventions for the experimental group were the first-generation EGFR-TKI erlotinib combined with bevacizumab (four studies) or ramucirumab (one study), and erlotinib monotherapy (four studies) or erlotinib plus placebo (one study) for the control group. All studies reached their primary study endpoints (i.e., PFS). Compared to erlotinib monotherapy, erlotinib plus antiangiogenic agents remarkably prolonged PFS [hazard ratio (HR) = 0.59, 95% confidence interval (CI) = 0.51-0.69, P = 0.000]; however, ORR, DCR, and OS were similar between the two groups. The overall grade 3-5 AEs increased in combination group (OR = 5.772, 95% CI = 2.38-13.94, P = 0.000), particularly the incidence of diarrhea (OR = 2.51, 95% CI = 1.21-5.23, P = 0.014), acneiform (OR = 1.815, 95% CI = 1.084-3.037, P = 0.023), hypertension (OR = 6.77, 95% CI = 3.62-12.66, P = 0.000), and proteinuria (OR = 13.48, 95% CI = 4.11-44.22, P = 0.000). Additionally, subgroup analysis demonstrated that Asian patients could significantly benefit from combination therapy (HR = 0.59, 95% CI = 0.50-0.69, P = 0.000). Patients with exon 19 deletions (HR = 0.61, 95% CI = 0.49-0.75, P = 0.000) and 21 Leu858Arg mutations (HR = 0.59, 95% CI = 0.47-0.73, P = 0.000) had almost equivalent PFS benefits when treated with double-blocking therapy. Patients with brain metastases at baseline in the combination group had a trend toward better PFS (HR = 0.55, 95% CI = 0.30-1.01, P = 0.001). Conclusions: Erlotinib plus bevacizumab or ramucirumab in EFGR-mutated NSCLC first-line setting yielded remarkable PFS benefits; however, this was accompanied by higher AEs. Epidermal growth factor receptor-TKI plus antiangiogenic agent therapy may be considered a new option for advanced EGFR-mutated NSCLC patients.
 ...
PMID:Efficacy and Safety of Epidermal Growth Factor Receptor (EGFR) Inhibitors Plus Antiangiogenic Agents as First-Line Treatments for Patients With Advanced EGFR-Mutated Non-small Cell Lung Cancer: A Meta-Analysis. 3271 57