THE GLOBAL CHALLENGE OF CHEMOTHERAPY TOXICITY: RETHINKING SUPPORTIVE CARE IN MODERN ONCOLOGY

Chemotherapy remains a central component of cancer treatment, yet its therapeutic efficacy is frequently overshadowed by a broad spectrum of systemic toxicities that severely compromise patient quality of life. This adverse effect – ranging from nausea, vomiting, and anorexia to mucositis, diarrhea, fatigue, and alopecia, are driven by complex molecular and cellular mechanisms that extend far beyond the direct cytotoxicity to malignant cells. Emerging evidence highlights the role of inflammatory cytokine cascades, oxidative stress, neurotransmitter imbalance, mitochondrial
dysfunction, and epithelial barrier disruption in mediating these side effects. For instance, serotonin release and 5-HT3 receptor activation underlie chemotherapy induced emesis, while hypothalamic dysregulation contributes to anorexia.
Mucositis results from ROS mediated NF-κB activation and epithelial apoptosis, whereas diarrhea is linked to SN-38 induced enterocyte damage, tight junction disruption, and microbiome imbalance. Fatigue stems from altered HPA axis
signalling and mitochondrial energy deficits, while alopecia arises from p53 mediated apoptosis in hair follicle keratinocytes. Understanding these multifaceted mechanisms provides a foundation for the development of targeted adjunct therapies, particularly those driven from biocompatible and multifunctional natural agents. This review presents an integrated molecular perspective on chemotherapy induced toxicities and explores innovative strategies for their prevention and management.