Targeting chemobrain: from experimental models to therapeutic discovery.

Authors

Nishant N Parikh, Hyung-Goo Kim, Amelia Michelle Sojung Moon, Sang Hoon Lee, Sang Hoon Kim, Euiyeon Lee, Mohammad Abdur Rashid, Yongkyu Park, X F Steven Zheng, Mi-Hyeon Jang

Published in

Drug discovery today. Pages 104764. Aug 11, 2026. Epub Aug 11, 2026.

Abstract

Chemotherapy-induced cognitive impairment affects a substantial proportion of cancer survivors and significantly diminishes quality of life, yet no FDA-approved therapies exist. Chemotherapeutic agents such as cisplatin, doxorubicin, paclitaxel and methotrexate induce oxidative stress, DNA damage, mitochondrial dysfunction and neuroinflammation, which disrupt synaptic plasticity and neurogenesis. Key pathways include PARP1 activation, NAD depletion, COX-2 signaling and adenosine A2A receptor dysregulation. Evidence from rodent and complementary models including Drosophila, zebrafish and Caenorhabditis elegans demonstrates conserved mechanisms. We highlight a multi-model discovery pipeline and discuss emerging therapeutic strategies targeting redox balance, mitochondrial function and neuroinflammatory pathways to mitigate cognitive decline in cancer survivors.

PMID:
42580437
Bibliographic data and abstract were imported from PubMed on 12 Aug 2026.

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