Tumour Targeting Strategies 2

What are the hallmarks of cancer that targeted therapies aim to disable?

1. Sustaining proliferative signaling

2. Evading growth suppressors

3. Avoiding immune destruction

4. Tumor-promoting inflammation

5. Inducing angiogenesis

6. Genome instability and mutation

7. Resisting cell death.

What is the role of EGFR inhibitors in cancer treatment?

"EGFR inhibitors (e.g., erlotinib, afatinib) block the EGFR protein, which is involved in signaling pathways that regulate growth, survival, and proliferation, leading to cell death in cancer cells that rely on EGFR."

What is the mechanism of action of CDK inhibitors like palbociclib?

"CDK inhibitors (e.g., palbociclib) suppress tumor growth by inhibiting cyclin-dependent kinases (CDKs), which regulate cell cycle progression, particularly in cancers with impaired Retinoblastoma (RB) pathway function."

How do immune checkpoint inhibitors like pembrolizumab work?

"Immune checkpoint inhibitors (e.g., pembrolizumab) block the interaction between PD-1 on T-cells and PD-L1 on cancer cells, reactivating T-cells to destroy cancer cells by preventing the inhibitory signal."

What is the role of COX-2 inhibitors like celecoxib in cancer treatment?

"COX-2 inhibitors (e.g., celecoxib) reduce tumor-promoting inflammation by inhibiting the COX-2 enzyme, which is involved in the production of pro-inflammatory mediators in cancers like colorectal and liver cancer."

How do anti-angiogenic therapies like bevacizumab work?

"Anti-angiogenic therapies (e.g., bevacizumab) inhibit vascular endothelial growth factor (VEGF) signaling, blocking the formation of new blood vessels to 'starve' tumors of oxygen and nutrients."

What is the role of PARP inhibitors in treating BRCA-mutated cancers?

"PARP inhibitors (e.g., olaparib) exploit synthetic lethality in BRCA-mutated cancers by blocking PARP-mediated DNA repair, leading to the accumulation of DNA damage and cancer cell death."

What is the mechanism of action of venetoclax in cancer treatment?

"Venetoclax is a BH3 mimetic that inhibits the anti-apoptotic molecule BCL-2, triggering apoptosis in cancer cells, particularly in certain types of leukemia."

What is synthetic lethality, and how is it used in cancer treatment?

"Synthetic lethality occurs when the loss of two genes (e.g., BRCA1/2 and PARP) leads to cell death. PARP inhibitors exploit this in BRCA-mutated cancers by blocking DNA repair, causing cancer cells to die while sparing normal cells."

What is synthetic dose lethality, and how does it differ from synthetic lethality?

"Synthetic dose lethality involves the overexpression of one gene (e.g., MYC) combined with the loss of another (e.g., Aurora A), leading to cell death. It differs from synthetic lethality, which involves the loss of two tumor suppressor genes."

What is lineage dependence, and how is it exploited in cancer treatment?

"Lineage dependence refers to the shared origin of cells or organs. In cancer treatment, it is exploited by targeting specific lineage-dependent pathways, such as androgen deprivation therapy in prostate cancer."

What is the role of androgen deprivation therapy in prostate cancer?

"Androgen deprivation therapy reduces testosterone levels, which prostate cancer cells depend on for growth, by blocking androgen synthesis or receptors, leading to tumor shrinkage."

What are the two main strategies for androgen deprivation therapy?

"1. Chemical blockage (e.g., leuprolide, abiraterone) to reduce testosterone production, 2. Androgen antagonists (e.g., bicalutamide, enzalutamide) to block androgen receptors."

What is the role of aromatase inhibitors in breast cancer treatment?

"Aromatase inhibitors (e.g., letrozole, anastrozole) reduce estrogen production by inhibiting the aromatase enzyme, which converts androgens to estrogen, making them effective in postmenopausal breast cancer patients."

What is the mechanism of action of selective estrogen receptor degraders (SERDs) like fulvestrant?

"SERDs (e.g., fulvestrant) competitively inhibit estrogen binding to the estrogen receptor and degrade the receptor, reducing estrogen signaling in breast cancer cells."

What is the role of tamoxifen in breast cancer treatment?

"Tamoxifen is a selective estrogen receptor modulator (SERM) that competitively binds to estrogen receptors, blocking estrogen's effects and inhibiting the growth of estrogen receptor-positive breast cancer."

What are the phases of clinical trials for cancer therapeutics?

"1. Phase I: Safety and dosage determination, 2. Phase II: Effectiveness and further safety evaluation, 3. Phase III: Tumor-specific efficacy and tolerability, 4. Phase IV: Post-marketing surveillance and additional risk-benefit analysis."

What are biomarkers, and how are they used in cancer treatment?

"Biomarkers are molecular indicators used to predict, diagnose, or monitor cancer. Examples include BRCA1/2 mutations for PARP inhibitors and EGFR mutations for EGFR inhibitors."

What is the role of BRCA1/2 mutations in predicting PARP inhibitor response?

"BRCA1/2 mutations impair DNA repair via homologous recombination, making cancer cells more sensitive to PARP inhibitors, which block alternative DNA repair pathways, leading to cell death."

What is the role of PD-1 inhibitors like pembrolizumab in cancer immunotherapy?

"PD-1 inhibitors (e.g., pembrolizumab) block the interaction between PD-1 on T-cells and PD-L1 on cancer cells, reactivating T-cells to attack and destroy cancer cells."