what are the major drawbacks of conventional chemotherapeutic agents?
DESCRIPTION
WHAT ARE THE MAJOR DRAWBACKS OF CONVENTIONAL CHEMOTHERAPEUTIC AGENTS?. 1. 2. 1. POOR SELECTIVITY. LOW THERAPEUTIC INDEX. 2. DRUG RESISTANCE. TARGETED AGENTS IN ANTICANCER CHEMOTHERAPY. ONCOGENE ACTIVATION. ONCOGENE ACTIVATION. TUMOR SUPPRESSOR INACTIVATION. 1) Point mutation. p53. - PowerPoint PPT PresentationTRANSCRIPT
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TARGETED AGENTS IN ANTICANCER CHEMOTHERAPY
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ONCOGENE ACTIVATION
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ONCOGENE ACTIVATION
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TUMOR SUPPRESSOR INACTIVATION
p53
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TUMOR SUPPRESSOR INACTIVATION
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Locus 9p21
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TUMOR SUPPRESSOR INACTIVATION
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Protein-protein interactions
TUMOR SUPPRESSOR INACTIVATION
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Weinstein IB and Joe AK (2006) Mechanisms of Disease: oncogene addiction—a 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
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Weinstein IB and Joe AK (2006) Mechanisms of Disease: oncogene addiction—a 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
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Weinstein IB and Joe AK (2006) Mechanisms of Disease: oncogene addiction—a 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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% B inhibition % B inhibition
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Cellula normale
Cellula tumorale
PTEN
INIBITORI DI mTOR
effetti lievi
attività PI3K/Akt/mTOR
attività PI3K/Akt/mTORPTEN
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Cellula normale
Cellula tumorale
BRCA1riparazione
BRCA1
SSBDSB
BER
HR
riparazioneSSBDSB
BER
HRInstabilità genomica
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Cellula normale
Cellula tumorale
BRCA1
riparazione
BRCA1
SSBDSB
BER
HR
SSBDSB
BER
HR
INIBITORI DI PARP
DSB riparazioneHR
INIBITORI DI PARP
DSBHR
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Cellula normale
Cellula tumorale
Rb
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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INHIBIT GENE EXPRESSION
INHIBIT PROTEIN FUNCTION
AS-ODN siRNA mAbs Small molecule inhibitors