# Molecular Mechanisms of Symptom Fluctuations in Malignant Tumor Patients: Stable by Day and Severe at Night

## TL;DR

This paper explores how symptoms in cancer patients worsen at night due to disrupted circadian rhythms and suggests using chronotherapy for better treatment.

## Contribution

The study links circadian gene disruptions to symptom fluctuations and proposes melatonin-based chronotherapeutic strategies.

## Key findings

- Disruptions in BMAL1 and PER genes correlate with worsened symptoms at night.
- Nocturnal tumor progression is linked to immune and metabolic dysregulation.
- Melatonin shows potential in optimizing circadian-based cancer treatments.

## Abstract

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.