Abstract
Melanoma is the most aggressive form of skin cancer and is notoriously resistant to all current modalities of cancer therapy. A large set of genetic, functional and biochemical studies suggest that melanoma cells become 'bullet proof' against a variety of chemotherapeutic drugs by exploiting their intrinsic resistance to apoptosis and by reprogramming their proliferation and survival pathways during melanoma progression. In recent years, the identification of molecules involved in the regulation and execution of apoptosis, and their alteration in melanoma, have provided new insights into the molecular basis for melanoma chemoresistance. With this knowledge in hand, the challenge is now to devise strategies potent enough to compensate or bypass these cell death defects and improve the actual poor prognosis of patients at late stages of the disease.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Apoptosis / physiology*
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Apoptotic Protease-Activating Factor 1
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Caspase 9
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Caspases / drug effects
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Caspases / metabolism
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Cell Survival / drug effects
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Cell Survival / physiology
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Disease Progression
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Drug Resistance, Neoplasm / physiology*
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Humans
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Inhibitor of Apoptosis Proteins
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Melanocytes / drug effects
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Melanoma / drug therapy*
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Melanoma / pathology*
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Microtubule-Associated Proteins / drug effects
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Microtubule-Associated Proteins / metabolism
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Mitochondria / drug effects
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Mitochondria / metabolism
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NF-kappa B / drug effects
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NF-kappa B / metabolism
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Neoplasm Proteins
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PTEN Phosphohydrolase
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Phosphoric Monoester Hydrolases / metabolism
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Proteins / drug effects
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Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / drug effects
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Signal Transduction
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Skin Neoplasms / drug therapy*
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Skin Neoplasms / pathology*
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Survivin
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Tumor Suppressor Protein p14ARF / drug effects
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Tumor Suppressor Protein p14ARF / metabolism
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Tumor Suppressor Proteins / metabolism
Substances
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APAF1 protein, human
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Antineoplastic Agents
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Apoptotic Protease-Activating Factor 1
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BIRC5 protein, human
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Inhibitor of Apoptosis Proteins
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Microtubule-Associated Proteins
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NF-kappa B
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Neoplasm Proteins
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Proteins
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Proto-Oncogene Proteins c-bcl-2
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Survivin
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Proteins
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase
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PTEN protein, human
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CASP9 protein, human
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Caspase 9
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Caspases