Mismatch repair deficiency is associated with resistance to DNA minor groove alkylating agents
1999
Mismatch Repair Deficiency and Drug Resistance
publication
Author Information
Author(s): Colella G, Marchini S, D'Incalci M, Brown R, Broggini M
Primary Institution: Molecular Pharmacology Unit, Istituto di Ricerche Farmacologiche ‘Mario Negri’
Hypothesis
Mismatch repair deficiency is associated with resistance to DNA minor groove alkylating agents.
Conclusion
Mismatch repair deficiency, particularly due to loss of hMLH1 expression, is linked to resistance against certain alkylating agents but not against non-covalent minor groove binders.
Supporting Evidence
- Mismatch repair deficiency is linked to resistance against major groove alkylating agents.
- The HCT-116+ch3 subline showed increased sensitivity to alkylating minor groove binders compared to the parental line.
- Cisplatin-resistant sublines of A2780 are more resistant to minor groove alkylators due to hMLH1 deficiency.
- Restoration of hMLH1 activity in A2780/CP70 increased sensitivity to minor groove alkylators.
Takeaway
Some cancer cells that can't fix DNA mistakes are harder to treat with certain drugs, but not all drugs are affected.
Methodology
The study used mismatch repair defective and proficient cell lines to test the sensitivity to various alkylating agents.
Digital Object Identifier (DOI)
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