Apoptotic versus genotoxic potential of anti-tumor agents: a concept of duality in unity.
Recent advances in anti-tumor therapy have raised a problem of secondary tumors and tumor resistance. Secondary tumors induced by chemotherapeutic agents as a consequence of primary therapy have poor prognostic outcome. Many new insights into molecular controls of cell cycle progression of normal and cancer cells can provide a useful framework in order to identify potential targets for anti-tumor therapies. One of the most promising strategies is the possibility to modulate apoptosis induced by anti-tumor agents. Cancer cell survival after chemotherapy will depend on specific checkpoints and/or repair pathways that have been lost, leading either to greater susceptibility to anti-tumor agents when the repair of damage is most important for survival or to greater resistance when the apoptotic response is more important. We have proposed a hypothesis that views survival and apoptotic processes (duality) in normal and tumor cells as genetically coupled (unity). We introduce, through a theoretical background, a new pathway of apoptotic inhibition. The proposed process of apoptotic inhibition is induced by mutation fixation in which recombination/repair processes (hRAD genes) play an important role. These coupled processes (duality in unity), to our view, underline tumor resistance by apoptotic inhibition and mutation fixation in normal cells exposed to anti-tumor agents.
ICN-Galenika Pharmaceuticals, Institute for Biomedical Research, Belgrade, Yugoslavia. vladapfd@ptt.edu
V
V
Bajic
Z
Z
Milicevic
B
B
Potpervic-Spremo
A
A
Nedeljkovic-Kurepa
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008962:Models, Theoretical; D009154:Mutation; D009369:Neoplasms / Q000473:pathology*; D011379:Prognosis; D011995:Recombination, Genetic
D000970:Antineoplastic Agents