Hanahan & Weinberg: The hallmarks of cancer. Cell 100:57-70, 2000

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Hanahan & Weinberg: The hallmarks of cancer. Cell 100:57-70, 2000. ONCOGENE ACTIVATION. ONCOGENE ACTIVATION. TUMOR SUPPRESSOR INACTIVATION. 1) Point mutation. p53. TUMOR SUPPRESSOR INACTIVATION. 1) Point mutation : p53, BRCA1 etc. 2) Deletion 3) Epigenetic silencing. Locus 9p21. - PowerPoint PPT Presentation

Transcript of Hanahan & Weinberg: The hallmarks of cancer. Cell 100:57-70, 2000

Hanahan & Weinberg:

The hallmarks of cancer. Cell 100:57-70, 2000

ONCOGENE ACTIVATION

ONCOGENE ACTIVATION

TUMOR SUPPRESSOR INACTIVATION

p53

TUMOR SUPPRESSOR INACTIVATION

Locus 9p21

TUMOR SUPPRESSOR INACTIVATION

Protein-protein interactions

TUMOR SUPPRESSOR INACTIVATION

Cellula normale

Cellula tumorale

PTEN

INIBITORI DI mTOR

effetti lievi

attività PI3K/Akt/mTOR

attività PI3K/Akt/mTORPTEN

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

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

% B inhibition % B inhibition

INIBIT GENE EXPRESSION

INIBIT PROTEIN FUNCTION

AS-ODN siRNA mAbs Small molecule inhibitors