A proposed mechanism for chemotherapy-related cognitive impairment ('chemo-fog')

Abstract

What is known and objective: Chemotherapeutic drugs for cancer treatment are, of necessity, cytotoxic. Unintended damage to normal central nervous system neuronal structure or function might lead to deleterious adverse effects on cognitive function, a mild form of which is reported by some cancer survivors. Understanding the physiologic connection between cancer chemotherapy and the reported cognitive dysfunction, could help inform choice of drugs, treatment regimens and new drug development. Our objective is to comment on a proposed mechanism for 'chemo-fog'.

Comment: An increasing number of patients are surviving cancer and are generating a new and rapidly growing category within the healthcare system. Some of these cancer survivors are reporting that they are experiencing residual and lingering effects from the cancer, or from its treatment, and that they now need care as survivors. This has given rise to the new field of 'survivor care'. Control of chemo-fog is an important aspect and understanding its mechanism, the basis for more rationale therapy. Such insight would also help direct drug-discovery efforts.

What is new and conclusion: New evidence suggests that 'chemo-fog' may be due to excessive cytokine release by the cytotoxic agents. Control of the elevated levels of the blood-brain-barrier-permeable pro-inflammatory cytokines, may help minimize this adverse effect.

Fig. 1

Illustration of a postulated link between a cancer chemotherapeutic drug (doxorubicin) and chemofog [highly simplified version of that presented in (7)].