Background Although DNA-directed alkylating\nagents and related compounds have been a mainstay in chemotherapeutic\nprotocols due to their ability to readily interfere\nwith the rapid mitotic progression of malignant cells, their\nclinical utility is limited by DNA repair mechanisms and immunosuppression.\nHowever, the same destructive nature of\nalkylation can be reciprocated at the cell surface using novel\nplasma membrane alkylating agents. Results Plasma membrane\nalkylating agents have elicited long term survival in\nmammalian models challenged with carcinomas, sarcomas,\nand leukemias. Further, a specialized group of plasma membrane\nalkylating agents known as tetra-O-acetate\nhaloacetamido carbohydrate analogs (Tet-OAHCs) potentiates\na substantial leukocyte influx at the administration and\nprimary tumor site, indicative of a potent immune response.\nThe effects of plasma membrane alkylating agents may be\nfurther potentiated through the use of another novel class of\nchemotherapeutic agents, known as dihydroxyacetone phosphate\n(DHAP) inhibitors, since many cancer types are known\nto rely on the DHAP pathway for lipid synthesis. Conclusion\nDespite these compelling data, preliminary clinical trials for\nplasma membrane-directed agents have yet to be considered.\nTherefore, this review is intended for academics and clinicians\nto postulate a novel approach of chemotherapy; altering critical\nmalignant cell signaling at the plasma membrane surface\nthrough alkylation, thereby inducing irreversible changes to\nfunctions needed for cell survival.
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