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Chem167_L17_May30

Chem167_L17_May30 - Cancer(cont Chapter 21 May 30 2013...

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Cancer’( con±t)’ Chapter’21’ May’30,’2013’
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h6p://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-03±845.pdf’
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Oncogenes and tumor suppressor genes Oncogenes’ ’ -’regulators’of’cellular’communicaKon’with’outside’environment’ ’ -’derived’through’mutaKon’of’ proto-oncogenes (regulaKon’of’ ’ homeostaKc’cell’funcKon’[cell’division’&’diFerenKaKon])’ ’ -’sKmulated’by’exposure’to’carcinogens’ ’ -’cause’cancer’when’sKmulated’(overexpressed,’wrongly’ expressed,’ etc)’ ’ -’ ras ,’ bcr-abl, abl-2, myc –’examples’of’(proto)oncogenes’ Tumor’suppressor’genes’(anK-oncogenes)’ ’ -’halt’uncontrolled’cellular’growth’ ’ -’promote’cancer’when’suppressed’or’inacKvated’ ’ -’ p53 ’and’ re±noblastoma (Rb) are’classic’examples’of’suppressor’ genes’
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Common defects in cancer Abnormal’signaling’ ’ expression’of’own’growth’factors’ ’ Extracellular’chemical’messengers’that’acKve’protein’kinase’receptors’in’the’cell’membrane’ ’ over-expression’of’growth-factor’receptors’or’their’acKvated’variants’(constantly’ON)’ ’ insensiKvity’to’growth’inhibiKon’ ’ ’
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Common defects in cancer Abnormal’signaling’ ’ expression’of’own’growth’factors’ ’ Extracellular’chemical’messengers’that’acKve’protein’kinase’receptors’in’the’cell’membrane’ ’ over-expression’of’growth-factor’receptors’or’their’acKvated’variants’(constantly’ON)’ ’ insensiKvity’to’growth’inhibiKon’ Abnormal’cell’cycle’regulaKon’ ’ cyclins’and’ cyclin-dependent’kinases’and’their’inhibitors’ ’ ’ Apoptosis’ disregulaKon’ ’ extrinsic’factors’–’molecular’signals’and’their’receptors’ ’ intrinsic’–’DNA’damage’ Abnormal’chromosome’maintenance’ ’ telomere’at’3±’end’of’chromosome,’stabilize’and’protect’the’DNA,’gets’shorter’during’each’replicaKon’ telomerase ’expression’to’keep’chromosome’ends’from’shrinking’ ’ ’ Abnormal’and’increased’angiogenesis’ ’ ’tumor’needs’good’blood’supply’ ’ ’as’tumor’grows,’needs’to’grow’its’own’vascularizaKon’system’via’extending’exisKng’capillaries’ ’’
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Therapeu5c approaches Surgery’and’radiaKon’–’local’but’far’from’perfect’ Systemic’Cancers:’ Chemotherapy’ ’ as’ Adjuvant therapy :’used’as’“insurance’policy”’a]er’surgery’and’radiaKon’ ’ anKneoplasKcs’–’anK’new’growth ’ ’ ’ poisons,’by’deFniKon’ ’ cytotoxic’compounds’–’interfere’with’synthesis’or’funcKon’of’DNA,’RNA,’ essenKal’proteins’
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