Mechanism of Resistance Flashcards
(22 cards)
What is the cellular uptake mechanism for Mechlorethamine?
Choline transporter
Mechlorethamine is an alkylating agent that requires specific transport mechanisms to enter cells.
What transporter is used by melphalan for cellular uptake?
Leucine transporter
Melphalan is another alkylating agent that relies on amino acid transporters.
Which transporter does Streptozotocin use for cellular uptake?
GLUT2 transporter
Streptozotocin is a nitrosourea that requires glucose transporters for cellular entry.
What is a common mechanism of resistance observed in anti-metabolites?
Increased detoxification via glutathione
Detoxification mechanisms can reduce the efficacy of various chemotherapeutic agents.
Which agents are known to alter CYP450 metabolism?
Cyclophosphamide, ifosfamide
Alterations in CYP450 can affect drug metabolism and resistance.
What are some methylating agents mentioned?
- Dacarbazine
- Procarbazine
These agents can also be affected by monoamine oxidase inhibitors.
Which inhibitors affect P450 enzymes?
- Ketoconazole
- Fluoroquinolones
- Cimetidine
- Erythromycin
These drugs can influence the metabolism of chemotherapeutic agents.
What is the role of the O6-methylguanine methyltransferase (MGMT) gene?
Encodes a protein that reverses alkylation
Cells overexpressing MGMT are more resistant to alkylating agents.
What is the relationship between MGMT promoter hypermethylation and glioma?
Better response to nitrosourea
Hypermethylation can enhance treatment efficacy in certain patients.
What does MMR repair deficiency lead to in terms of drug sensitivity?
Reduced sensitivity to alkylators
Mismatch repair deficiencies can impact treatment outcomes.
What is the function of the MDR-1 gene phenotype?
Codes for ABC / P-glycoprotein
This protein is involved in drug efflux and can confer resistance to various drugs.
Which drugs are affected by the MDR-1 gene phenotype?
- Anthracyclines
- Antracenediones
- Actinomycin D
These classes of drugs can be expelled from cells, reducing their effectiveness.
What is a consequence of topoisomerase II mutation?
Decrease in topoisomerase II activity
Such mutations can lead to resistance against certain chemotherapeutics.
What effect do PARP inhibitors have on anthracyclines?
Inhibit the activity of topoisomerase II
This interaction can affect the efficacy of both classes of drugs.
What leads to Ara-C resistance?
Decreased deoxycytidine kinase activity
Diminished activation of this enzyme is a key resistance mechanism.
What contributes to 5-FU resistance?
Increased DPD (dihydropyrimidine dehydrogenase)
Elevated levels of this enzyme can deactivate 5-FU, a common chemotherapeutic agent.
What is the mechanism of increased efflux in anti-microtubules?
MDR, similar to anthracyclines
Drug resistance can occur through enhanced drug expulsion mechanisms.
What alteration occurs in tubulin that affects drug sensitivity?
Tubulin alteration stabilizes microtubules
This stabilization can negate the effects of vinca alkaloids while potentially increasing sensitivity to taxanes.
Which transporter is used by platinum analogues?
Copper transporter (CTR1)
This transporter is critical for the cellular uptake of platinum-based drugs.
What is the role of ERCC1 in platinum analogue resistance?
Increased DNA repair via nucleotide excision repair
Enhanced repair mechanisms can reduce the effectiveness of platinum agents.
What is lesion tolerance in the context of DNA replication?
DNA continues to replicate by skipping over lesions
This mechanism allows cells to bypass damage, impacting treatment responses.
What contributes to drug inactivation in resistance mechanisms?
Glutathione and metallothionein
These substances can bind and inactivate various chemotherapeutic agents, similar to alkylators.
