Journal of CancerMar 23, 2026

Molecular Causes of Symptom Changes in Cancer Patients: Stable During the Day and Worse at Night

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

This review argues that circadian clock disruption may help explain why malignant tumor symptoms worsen at night.

Evidence

This mechanistic review links BMAL1/PER disruption, metabolic, immune, and endocrine dysregulation to nocturnal tumor activity and symptom pathways including invasion, neural infiltration, inflammation, DRG sensitization, and melatonin changes.

Caveat

It synthesizes proposed mechanisms and chronotherapeutic strategies rather than testing symptom timing or treatments in a patient trial.

Simplified

Patients with malignant tumors often experience fluctuations in the severity of their symptoms depending on the time of day. In traditional Chinese medicine, symptoms are said to follow a pattern of "mild in the morning, stable by day, worsening in the evening, and severe at night." This article investigates the circadian chronobiology of symptoms and examines their molecular pathophysiology. Evidence suggests that disruptions in core circadian clock genes, such as BMAL1 and PER, along with the dysregulation of cellular metabolic pathways, immune responses, and endocrine functions, synergistically facilitate tumor growth and metastasis during nocturnal periods. These molecular alterations contribute to symptom exacerbation through mechanisms which include direct tumor invasion, neural infiltration, inflammatory processes, dorsal root ganglion (DRG) sensitization, and abnormal melatonin secretion. The article further explores three chronotherapeutic strategies and assesses melatonin's role in targeted oncological therapy, aiming to optimize circadian regulation and symptom management, thereby providing a scientific foundation for personalized anti-tumor interventions that are based on circadian rhythms.