WHAT ARE THE MAJOR DRAWBACKS OF CONVENTIONAL CHEMOTHERAPEUTIC AGENTS?
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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.

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What are the major drawbacks of conventional chemotherapeutic agents

WHAT ARE THE MAJOR DRAWBACKS OF CONVENTIONAL CHEMOTHERAPEUTIC AGENTS?

1

2


What are the major drawbacks of conventional chemotherapeutic agents

1 CHEMOTHERAPEUTIC AGENTS?

POOR SELECTIVITY

LOW THERAPEUTIC INDEX


What are the major drawbacks of conventional chemotherapeutic agents

2 CHEMOTHERAPEUTIC AGENTS?

DRUG RESISTANCE


What are the major drawbacks of conventional chemotherapeutic agents

TARGETED AGENTS IN CHEMOTHERAPEUTIC AGENTS?

ANTICANCER CHEMOTHERAPY


What are the major drawbacks of conventional chemotherapeutic agents

ONCOGENE ACTIVATION CHEMOTHERAPEUTIC AGENTS?


What are the major drawbacks of conventional chemotherapeutic agents

ONCOGENE ACTIVATION CHEMOTHERAPEUTIC AGENTS?


What are the major drawbacks of conventional chemotherapeutic agents

TUMOR SUPPRESSOR INACTIVATION CHEMOTHERAPEUTIC AGENTS?

1) Point mutation

p53


What are the major drawbacks of conventional chemotherapeutic agents

TUMOR SUPPRESSOR INACTIVATION CHEMOTHERAPEUTIC AGENTS?

1) Point mutation: p53, BRCA1 etc.

2) Deletion

3) Epigeneticsilencing


What are the major drawbacks of conventional chemotherapeutic agents

Locus 9p21 CHEMOTHERAPEUTIC AGENTS?


What are the major drawbacks of conventional chemotherapeutic agents

TUMOR SUPPRESSOR INACTIVATION CHEMOTHERAPEUTIC AGENTS?

1) Point mutation: p53, BRCA1 etc.

2) Deletion

3) Epigeneticsilencing

4) Protein-proteininteractions


What are the major drawbacks of conventional chemotherapeutic agents

TUMOR SUPPRESSOR INACTIVATION CHEMOTHERAPEUTIC AGENTS?

Protein-protein interactions


What are the major drawbacks of conventional chemotherapeutic agents

Table 1 CHEMOTHERAPEUTIC AGENTS?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


What are the major drawbacks of conventional chemotherapeutic agents

Table 2 CHEMOTHERAPEUTIC AGENTS?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


What are the major drawbacks of conventional chemotherapeutic agents

Table 3 CHEMOTHERAPEUTIC AGENTS?Clinical evidence of oncogene addiction

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


What are the major drawbacks of conventional chemotherapeutic agents

MODELS OF ONCOGENE ADDICTION CHEMOTHERAPEUTIC AGENTS?


What are the major drawbacks of conventional chemotherapeutic agents

MODELS OF ONCOGENE ADDICTION CHEMOTHERAPEUTIC AGENTS?


What are the major drawbacks of conventional chemotherapeutic agents

MODELS OF ONCOGENE ADDICTION CHEMOTHERAPEUTIC AGENTS?


What are the major drawbacks of conventional chemotherapeutic agents

Two CHEMOTHERAPEUTIC AGENTS?genes (‘A’ and ‘B’) are said to be synthetic lethal if mutation of either gene alone is compatible with viability but simultaneous mutation of both genes causes death.


What are the major drawbacks of conventional chemotherapeutic agents

% B inhibition CHEMOTHERAPEUTIC AGENTS?

% B inhibition


What are the major drawbacks of conventional chemotherapeutic agents

Cellula normale CHEMOTHERAPEUTIC AGENTS?

PTEN

Cellula tumorale

PTEN

effetti lievi

attività PI3K/Akt/mTOR

INIBITORI DI mTOR

attività PI3K/Akt/mTOR


What are the major drawbacks of conventional chemotherapeutic agents

Cellula normale CHEMOTHERAPEUTIC AGENTS?

BRCA1

BRCA1

Cellula tumorale

BER

SSB

riparazione

DSB

HR

BER

SSB

riparazione

DSB

Instabilità genomica

HR


What are the major drawbacks of conventional chemotherapeutic agents

Cellula normale CHEMOTHERAPEUTIC AGENTS?

BRCA1

BRCA1

Cellula tumorale

INIBITORI DI PARP

BER

DSB

riparazione

SSB

HR

DSB

riparazione

HR

INIBITORI DI PARP

BER

HR

SSB

DSB

DSB

HR


What are the major drawbacks of conventional chemotherapeutic agents

Cellula normale CHEMOTHERAPEUTIC AGENTS?

Rb

Rb

Cellula tumorale

SOPRAVVIVENZA

blocco attività E2F

VELENI DELLA TOPO II

 espressione gene A

 espressione gene topoisomerasi II

 attività E2F

 espressione gene B

 espressione gene C


What are the major drawbacks of conventional chemotherapeutic agents

HOW CAN WE SELECTIVELY TARGET TUMOR RELEVANT DEFECTS? CHEMOTHERAPEUTIC AGENTS?

INHIBIT GENE EXPRESSION

INHIBIT PROTEIN FUNCTION

Small molecule inhibitors

AS-ODN

mAbs

siRNA