Abstract
BackgroundDespite great advances in clinical oncology, the molecular mechanisms underlying the failure of chemotherapeutic intervention in treating lymphoproliferative and related disorders are not well understood.HypothesisA hypothetical scheme to explain the damage induced by chemotherapy and associated chronic oxidative stress is proposed on the basis of published literature, experimental data and anecdotal observations. Brief accounts of multidrug resistance, lymphoid malignancy, the cellular and molecular basis of autoimmunity and chronic oxidative stress are assembled to form a basis for the hypothesis and to indicate the likelihood that it is valid in vivo.ConclusionThe argument set forward in this article suggests a possible mechanism for the development of autoimmunity. According to this view, the various sorts of damage induced by chemotherapy have a role in the pattern of drug resistance, which is associated with the initiation of autoimmunity.
Highlights
Despite great advances in clinical oncology, the molecular mechanisms underlying the failure of chemotherapeutic intervention in treating lymphoproliferative and related disorders are not well understood.Hypothesis: A hypothetical scheme to explain the damage induced by chemotherapy and associated chronic oxidative stress is proposed on the basis of published literature, experimental data and anecdotal observations
In the context of the hypothesis proposed here, it is possible that a host overloaded with one or more antigenic determinants from one or more infectious agents causes stress that in turn activates toll-like receptors (TLRs)
It is contended that by a yet uncharacterized mechanism, this could lead to multi-drug resistance during the course of treatment for these infections, and this could develop into autoimmunity
Summary
The argument set forward in this article suggests a possible mechanism for the development of autoimmunity. In the context of the hypothesis proposed here (see below), it is possible that a host overloaded with one or more antigenic determinants (epitopes) from one or more infectious agents causes stress that in turn activates TLRs. It is contended that by a yet uncharacterized mechanism, this could lead to multi-drug resistance during the course of treatment for these infections, and this could develop into autoimmunity. It is suggested that increased expression of prosurvival genes enables tumor cells to evade chemotherapeutically-induced cytotoxicity, conferring an adaptive growth advantage that aggravates the tendency of tumor cells with MDR to repopulate the tumor burden This leads to relapse and the subsequent development of autoimmunity via several chronic redox state-dependent reaction cascades. Therapeutic measures directed at modulating such epigenetic mechanism(s) in a development stage-specific manner (lymphoproliferative disorder) would potentially attenuate the impact of drugs and the subsequent evolution of autoimmune disorders
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
