what are the major drawbacks of conventional chemotherapeutic agents?

TARGETED AGENTS IN ANTICANCER CHEMOTHERAPY

ONCOGENE ACTIVATION

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 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

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

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

% B inhibition % B inhibition

Cellula normale

Cellula tumorale

PTEN

INIBITORI DI mTOR

effetti lievi

attività PI3K/Akt/mTOR

attività PI3K/Akt/mTORPTEN

Cellula normale

Cellula tumorale

BRCA1riparazione

BRCA1

SSBDSB

BER

HR

riparazioneSSBDSB

BER

HRInstabilità genomica

Cellula normale

Cellula tumorale

BRCA1

riparazione

BRCA1

SSBDSB

BER

HR

SSBDSB

BER

HR

INIBITORI DI PARP

DSB riparazioneHR

INIBITORI DI PARP

DSBHR

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

INHIBIT GENE EXPRESSION

INHIBIT PROTEIN FUNCTION

AS-ODN siRNA mAbs Small molecule inhibitors