**11. Targeting MMR and Synthetic Lethality Interactions: Possible New Combination Therapies**

Defects in MMR genes confer resistance to platinum-based chemotherapy and re-expression of these components restores sensitivity to these compounds [169]. Although not many specific drugs that inhibit MMR genes have been proposed, it has been shown that Pol-β inhibition is synthetically lethal with MSH2/MLH1 deficiencies, likely because this inhibition determines accumulation of unrepaired oxidized nucleotides, which increases the amount of mismatches. Thus, Pol-β inhibitors (NSC666715) are promising agents for treatment of MMR-deficient cancers in combination with DNA-alkylating agents such as temozolomide (Table 5) [170].

**13. Conclusions**

the occurrence of drug resistance.
