Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Single-agent chemotherapy has shown limited activity as second-line treatment in metastatic non-small cell lung cancer (NSCLC), with short-lived responses and modest survival benefit over best supportive care or placebo. There are multiple ways to improve the poor outcome of patients whose disease progresses after first-line chemotherapy. First, individualizing second-line chemotherapy could optimize its effect; the discovery of dramatic responses and significant improvement in survival in patients with epidermal growth factor receptor (EGFR) gene mutations who are treated with EGFR tyrosine kinase inhibitors may lead to the application of other novel therapeutic approaches. Cancer vaccines, using autologous tumor cells genetically modified with granulocyte-macrophage colony-stimulating factor, constitute a new therapeutic option for patients with chemoresistant advanced NSCLC. Vaccines based on lymphocyte-defined tumor antigens, such as melanoma-associated antigen-3, toll-like receptor 9, and mucin 1, are also in the first stages of testing and have shown promising preliminary results. New approaches in gene therapy, including a p53-based method, are currently being investigated. The ultimate goal of gene therapy is to target cancerous stem cells, the importance of which is beginning to be recognized in NSCLC through the study of abnormalities in the wingless (Wnt) pathway. At the preclinical level, small interfering RNA sequences have been used successfully to neutralize multiple abnormal components of the Wnt pathway.
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PMID:Future directions in the second-line treatment of non-small cell lung cancer. 1647 9

PANVAC is a cancer vaccine therapy delivered through two viral vectors--recombinant vaccinia and recombinant fowlpox--which are given sequentially. Both vectors contain transgenes for the tumor-associated antigens epithelial mucin 1 and carcinoembryonic antigen, which are altered or overexpressed in most carcinomas. The vectors also contain transgenes for three human T cell costimulatory molecules required to enhance immune response: B7.1, intracellular adhesion molecule-1 and leukocyte function-associated antigen-3. PANVAC is injected subcutaneously and processed by the body's antigen-presenting cells. Preclinical studies have demonstrated the efficacy of PANVAC in inducing both carcinoembryonic antigen- and mucin 1-specific cytotoxic T lymphocyte responses in vitro and in murine models. Other strategies that enhance the immune response include the use of granulocyte-macrophage colony-stimulating factor and a prime-boost administration sequence. Clinical trials have demonstrated PANVAC's safety and its ability to induce antigen-specific T cell responses. Early clinical trials are evaluating PANVAC alone and in combination with conventional chemotherapy and/or radiation. Studies to date hold promise for the use of PANVAC as a means to stimulate the immune system against malignancies and to provide clinical benefit.
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PMID:PANVAC-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma. 1737 5