TARGETED AGENTS IN ANTICANCER CHEMOTHERAPY
ONCOGENE ACTIVATION
TUMOR SUPPRESSOR INACTIVATION p53
TUMOR SUPPRESSOR INACTIVATION
Locus 9p21
TUMOR SUPPRESSOR INACTIVATION
Protein-protein interactions TUMOR SUPPRESSOR INACTIVATION
Weinstein IB and Joe AK (2006) Mechanisms of Disease: oncogene addictiona rationale for molecular targeting in cancer therapy Nat Clin Pract Oncol 3: 448– /ncponc0558 Table 1 Examples of oncogene addiction: studies in mice
Weinstein IB and Joe AK (2006) Mechanisms of Disease: oncogene addictiona rationale for molecular targeting in cancer therapy Nat Clin Pract Oncol 3: 448– /ncponc0558 Table 2 Examples of oncogene addiction: studies in human cancer cell lines
Weinstein IB and Joe AK (2006) Mechanisms of Disease: oncogene addictiona rationale for molecular targeting in cancer therapy Nat Clin Pract Oncol 3: 448– /ncponc0558 Table 3 Clinical evidence of oncogene addiction
% B inhibition
Cellula normale Cellula tumorale PTEN INIBITORI DI mTOR effetti lievi attività PI3K/Akt/mTOR attività PI3K/Akt/mTOR PTEN
Cellula normale Cellula tumorale BRCA1 riparazione BRCA1 SSB DSB BER HR riparazione SSB DSB BER HR Instabilità genomica
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
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
INHIBIT GENE EXPRESSION INHIBIT PROTEIN FUNCTION AS-ODN siRNA mAbs Small molecule inhibitors