Medical Research: Emerging Concepts and Applications Vol. 1

The improved survival rates made possible through advances in cancer treatment have brought to light a range of long-term sequelae that profoundly affect patient quality of life. Among these, cancer-related cognitive impairment (CRCI) stands out as particularly prevalent and debilitating.

Chemotherapy-induced cognitive impairment, also known as cancer-related cognitive impairment (CRCI), commonly referred to as “chemo brain” or “brain fog”, is a common consequence of cancer treatment, affecting domains such as memory, attention, executive function, and processing speed. Initially described mainly in patients receiving chemotherapy, CRCI is now known to occur across multiple cancer types and treatment modalities, including hormonal, targeted, and immune-based therapies. A substantial proportion of cancer survivors report persistent cognitive difficulties that can last for months or years after therapy. The effects of CRCI can range from very mild to severe, significantly impacting daily functioning and quality of life.

Emerging evidence highlights a multifactorial biological basis for CRCI, involving neuroinflammation, oxidative stress, mitochondrial dysfunction, and direct neurotoxic effects of chemotherapeutic agents, as well as transcriptomic alterations that disrupt neuronal signalling and plasticity. Two principal pathways leading to CRCI can be recognised: direct CNS toxicity despite the blood–brain barrier, and indirect toxicity mediated by cytokines released from tumour and normal tissues in response to chemotherapeutic drugs. Both can induce neuroinflammation, reduce hippocampal neurogenesis, and affect grey- and white-matter density in the frontal and temporal areas.

Recent transcriptomic studies reveal widespread changes in genes regulating immune activation, synaptic integrity, and metabolic pathways, suggesting that chemotherapy perturbs both central nervous system homeostasis and neuroimmune communication.

Most studies have focused on breast cancer patients treated with anthracyclines. This population includes many long-term survivors and has a high reported incidence of CRCI. However, anthracyclines are only one of many chemotherapeutic drugs that can lead to this syndrome.

Given the growing number of cancer survivors, understanding the mechanisms underlying CRCI is essential for developing targeted interventions.

This comprehensive review summarises epidemiological trends, mechanistic insights, molecular fundamentals, diagnostic hurdles, and therapeutic innovations in CRCI, advocating for routine screening in clinical guidelines (e.g., ASCO survivorship updates). Future directions include longitudinal biobanking initiatives, AI-driven predictive modelling for at-risk patients, development of targeted neuroprotectants (e.g., anti-inflammatory biologics, antidepressants), and inclusive trials addressing underrepresented groups. Ongoing research into molecular signatures and neurobiological pathways holds promise for refining diagnostic criteria and guiding the development of mechanism-based therapeutics. Although no conventionally accepted treatment is available, as cancer therapies evolve toward precision medicine, mitigating CRCI is critical to optimising functional outcomes in the growing survivor population.