Lecture 11 pharmacology of cytotoxins III Flashcards
Describe Tamoxifen’s mechanism of action as a selective estrogen receptor modulator.
Tamoxifen is a partial antagonist of the estrogen receptor. It acts as an agonist inhibitor of estradiol at the estrogen receptor, initially halting the proliferation of breast cancer cells.
What is the mechanism of action of Fulvestrant in treating ER positive advanced breast cancer?
Fulvestrant is an estrogen receptor antagonist that binds to the ER, leading to rapid degradation of the ER complex. It impairs ER dimerization and does not have downstream effects on gene expression.
How does Letrozole function as an aromatase inhibitor in breast cancer treatment?
Letrozole inhibits the aromatase enzyme, blocking the aromatization of androgens. It is a third-generation drug with high specificity for aromatase, preventing the conversion of androgens to estrogens.
Define the role of ER as a biomarker in predicting response to endocrine therapy in breast cancer.
ER (estrogen receptor) is a predictive test for endocrine therapy in breast cancer. Approximately 70% of breast cancers are ER-positive, and patients with ER-positive tumors have a higher response rate to treatments like tamoxifen or aromatase inhibitors.
Describe the mechanism of action of Flutamide as an anti-androgen in treating metastatic prostate cancer.
Flutamide is an androgen receptor antagonist that inhibits the androgen receptor, preventing the upregulation of androgen response genes. It also accelerates the degradation of the androgen receptor.
What are Bioreductive Agents and how do they function in cancer treatment?
Bioreductive Agents are drugs that require reduction to form active cytotoxic species. They undergo bioreductive metabolism in the absence of oxygen, with bioreductive enzymes often overexpressed in cancer cells.
Describe the concept of synthetic lethality in cancer cells.
It arises when mutations in two or more genes lead to cell death, making normal cells with wild-type genes survive while mutated cells die.
What is the role of BRCA1/BRCA2 genes in DNA repair?
They are important for repairing double-strand breaks in DNA.
Define PARP and its significance in cancer treatment.
PARP (Poly ADP-ribose polymerase) is a protein involved in DNA repair. Inhibition of PARP in BRCA-mutated cancer cells leads to accumulation of DNA lesions, causing cell death.
How does OLAPARIB function in cancer treatment?
OLAPARIB is the first approved PARP inhibitor. It selectively kills cancer cells with BRCA mutations by preventing DNA repair, leading to cell death.
Explain the role of DNA damage and repair pathways in cell survival.
Cells with DNA damage activate various repair pathways like mismatch repair, base-excision repair, and homologous recombination to maintain genomic integrity and survival.
