Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Head and neck squamous cell carcinoma (HNSCC) of multi-factorial etiopathogenesis is rising worldwide. Treatment-associated toxicity problems and treatment failure in advanced disease stages with conventional therapies have necessitated a focus on alternative strategies. Molecular targeted therapy, with the potential for increased selectivity and fewer adverse effects, hold promise in the treatment of HNSCC. In an attempt to improve outcomes in HNSCC, targeted therapeutic strategies have been developed. These strategies are focusing on the molecular biology of HNSCC in an attempt to target selected pathways involved in carcinogenesis. Inhibiting tumor growth and metastasis by focusing on specific protein or signal transduction pathways or by targeting the tumor microenvironment or vasculature are some of the new approaches. Targeted agents for HNSCC expected to improve the effectiveness of current therapy include EGFR inhibitors (Cetuximab, Panitumumab, Zalutumumab), EGFR tyrosine kinase inhibitors (Gefitinib, Erloitinib), VEGFR inhibitors (Bevacizumab, Vandetanib), and various inhibitors of, e.g., Src-family kinase, PARP, proteasome, mTOR, COX, and heat shock protein. Moreover, targeted molecular therapy can also act as a complement to other existing cancer therapies. Several studies have demonstrated that the combination of targeting techniques with conventional current treatment protocols may improve the treatment outcome and disease control, without exacerbating the treatment related toxicities. Some of the targeted approaches have been proved as promising therapeutic potentials and are already in use, whereas remainder exhibits mixed result and necessitates further studies. Identification of predictive biomarkers of resistance or sensitivity to these therapies remains a fundamental challenge in the optimal selection of patients most likely to benefit from targeted treatment.
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PMID:Targeted therapy in head and neck cancer. 2237 81

Lung cancer is the most common form of the disease and the leading cause of cancer deaths worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancers. Forty percent of all cases present with stage III, and many of them are considered inoperable (staged IIIA with mediastinal lymph node involvement) or stage IIIB disease. Concurrent platinum-based chemotherapy and thoracic radiation has demonstrated survival benefits in these patients. We review the role of new target agents in combination with radiotherapy in stage III NSCLC. Antiangiogenics improve tumor oxygenation thereby improving the therapeutic efficacy of irradiation in models. Bevacizumab in combination with thoracic radiation has shown high toxicity. However, other antiangiogenic agents are more promising. Radiation activates epidermal growth factor receptor (EGFR) pathways, inducing radioresistance, cell proliferation and enhanced DNA repair. After promising data from preclinical models and early clinical trials, cetuximab did not show any benefit in a recent phase III trial. Panitumumab and nimotuzumab are under evaluation. Gefitinib has been investigated in combination with radiotherapy for unresectable stage III NSCLC, but results in maintenance treatment after chemoradiotherapy were not encouraging. Erlotinib has also been tested in a phase II trial with chemoradiotherapy. Other new pathways and agents are being studied, such as m-TOR pathway, bortezomib, heat shock protein 90 (Hsp90) inhibition, histone deacetylase inhibitors (HDACS), aurora kinases, mitogen activated protein kinases (MARK) and PARP inhibitors.
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PMID:Therapeutic integration of new molecule-targeted therapies with radiotherapy in lung cancer. 2580 86