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

The history of specific therapy for hereditary tumors dates back to mid 1980s and involves a number of reports demonstrating regression of familial colon polyps upon administration of sulindac. Virtually no clinical studies on other hereditary cancer types were available until the year 2009, when Byrski et al. presented the data on unprecedented sensitivity of BRCA1-associated breast malignancies to cisplatin. This breakthrough has revived interest to the treatment of cancer in germ-line mutation carriers. Recent trials and clinical observations have confirmed the efficacy of platinating agents and PARP inhibitors in BRCA1/2-driven breast, ovarian and pancreatic carcinomas. Pegylated liposomal doxorubicin may be considered as a promising treatment option for BRCA1/2-related ovarian cancer after the failure of platinum-containing therapy. Several novel drugs have been recently introduced in the management of rare familial tumor syndromes. Vandetanib, a low-molecular weight RET kinase inhibitor, demonstrated substantial efficacy in the treatment of hereditary and sporadic medullary thyroid cancer. Vismodegib, an inhibitor of SMO oncoprotein, caused regression of basal-cell carcinomas in patients with Gorlin syndrome. Down-regulation of mTOR kinase by everolimus has been successfully used for the therapy of subependymal giant-cell astrocytomas in patients with tuberous sclerosis. The achievements in the prevention, diagnostics and treatment of hereditary cancers may serve as an excellent example of triumph of translational medicine.
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PMID:Systemic treatment for hereditary cancers: a 2012 update. 2354 33