TARGETED AGENTS IN ANTICANCER CHEMOTHERAPY.

Presentazione sul tema: "TARGETED AGENTS IN ANTICANCER CHEMOTHERAPY."— Transcript della presentazione:

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4 TARGETED AGENTS IN ANTICANCER CHEMOTHERAPY

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6 ONCOGENE ACTIVATION

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8 TUMOR SUPPRESSOR INACTIVATION p53

9 TUMOR SUPPRESSOR INACTIVATION

10 Locus 9p21

11 TUMOR SUPPRESSOR INACTIVATION

12 Protein-protein interactions TUMOR SUPPRESSOR INACTIVATION

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15 Weinstein IB and Joe AK (2006) Mechanisms of Disease: oncogene addictiona rationale for molecular targeting in cancer therapy Nat Clin Pract Oncol 3: 448–457 10.1038/ncponc0558 Table 1 Examples of oncogene addiction: studies in mice

16 Weinstein IB and Joe AK (2006) Mechanisms of Disease: oncogene addictiona rationale for molecular targeting in cancer therapy Nat Clin Pract Oncol 3: 448–457 10.1038/ncponc0558 Table 2 Examples of oncogene addiction: studies in human cancer cell lines

17 Weinstein IB and Joe AK (2006) Mechanisms of Disease: oncogene addictiona rationale for molecular targeting in cancer therapy Nat Clin Pract Oncol 3: 448–457 10.1038/ncponc0558 Table 3 Clinical evidence of oncogene addiction

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22 % B inhibition

23 Cellula normale Cellula tumorale PTEN INIBITORI DI mTOR effetti lievi attività PI3K/Akt/mTOR attività PI3K/Akt/mTOR PTEN

24 Cellula normale Cellula tumorale BRCA1 riparazione BRCA1 SSB DSB BER HR riparazione SSB DSB BER HR Instabilità genomica

25 Cellula normale Cellula tumorale BRCA1 riparazione BRCA1 SSB DSB BER HR SSB DSB BER HR INIBITORI DI PARP DSB riparazione HR INIBITORI DI PARP DSB HR

26 Cellula normale Cellula tumorale Rb attività E2F espressione gene A espressione gene B espressione gene topoisomerasi II espressione gene C VELENI DELLA TOPO II SOPRAVVIVENZA blocco attività E2F

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29 INHIBIT GENE EXPRESSION INHIBIT PROTEIN FUNCTION AS-ODN siRNA mAbs Small molecule inhibitors