Gene/Protein Disease Symptom Drug Enzyme Compound
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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.
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PMID:Targeted therapy in rectal cancer. 1791 Mar 11

Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), was the first angiogenesis inhibitor approved for the first-line treatment of metastatic colorectal cancer in combination with intravenous fluorouracil-based chemotherapy. Two major cohort studies--BRiTE and BEAT--reported a 2% incidence of bowel perforation, which remains a rare, but serious, complication of bevacizumab treatment. Late anastomotic complications, arising > 3 months after surgery, are emerging occurrences that may be associated with bowel perforation. We report here on such a case caused by pazopanib, a new antiangiogenic agent, and also include a review of the published cases in the literature (n = 23) and an analysis of their management. Proctectomy was the initial surgery in 17 patients (74%) with rectal cancer, and 13 of these patients had undergone adjuvant radiation prior to surgery. The majority (84%) of the complications occurred with antiangiogenic treatment after a mean number of four cycles. Patients' management was invariably associated with withdrawal of the antiangiogenic agent, together with conservative treatment in 14 patients (66%).
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PMID:Late anastomotic colonic dehiscence due to antiangiogenic treatment, a specific drug-class complication requiring specific treatment: an example of pazopanib complication. 2180 88

Ramucirumab is an antiangiogenic agent targeting vascular endothelial growth factor receptor (VEGF)-2 that has been approved for second-line treatment of patients with metastatic colorectal cancer. VEGF-targeted therapy has various distinctive adverse effects owing to its antitumour effects. However, little is known with regard to its skin toxicity, such as its ability to cause skin ulcers. We report a case of large skin ulceration around a colostomy and delayed healing caused by ramucirumab. A 58-year-old patient diagnosed with rectal cancer with liver and lung metastases. He was administered folinic acid, fluorouracil (5-FU), and oxaliplatin (FOLFOX) and bevacizumab as first-line treatment. A laparoscopic colostomy was performed for suspected worsening of the bowel obstruction. He was then administered folinic acid, 5 fluorouracil, and irinotecan (FOLFIRI) and ramucirumab as second-line treatment after surgery. However, dehiscence and a small skin ulceration caused by ramucirumab developed around the colostomy which increased in size and became necrotic; therefore, he was administered only FOLFIRI, without ramucirumab. The ulcer decreased in size slightly with surgical debridement and showering. He resumed FOLFIRI and ramucirumab.
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PMID:Large Skin Ulcer and Delayed Wound Healing around a Colostomy in a Patient with Metastatic Colorectal Cancer Receiving Vascular Endothelial Growth Factor Receptor-2 Inhibitor Therapy. 3118 53