Chronobiology of the Tumor Microenvironment: Implications for Therapeutic Strategies and Circadian-Based Interventions

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Numerous research works have emphasized the critical role that circadian rhythm plays in tumor microenvironment (TME). The goal of clarifying chrono-pharmacological strategies for improving cancer treatment clinical settings is a continuous endeavor. Consequently, to enhance use time-based pharmaceutical therapies oncology, combining existing knowledge on rhythms' roles within TME essential. This perspective elucidates functions rhythms across various stages development, progression, and metastasis. Specifically, aging, angiogenesis, inflammation are implicated modulating TME. Furthermore, exerts profound influence current treatments thereby generates chronotheray manage tumors. From perspective, offers promising opportunities prevention treatment; nevertheless, further study needed address unanswered scientific problems.

Language: Английский

---

5-Fluorouracil Toxicity: Revisiting the Relevance of Pharmacokinetic Parameters

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(5), P. 653 - 653

Published: April 29, 2025

Background/Objectives: 5-fluorouracil (5-FU) is used in the treatment of solid cancer types. Because its narrow therapeutic window, drug monitoring recommended. We were confronted to answer a question on relevance concentration as opposed area under plasma concentration–time curve (AUC) predict toxicity when we had assess case patient who died after an erroneously high infusion rate. Methods: physiologically-based pharmacokinetic modeling (PBPK) simulate profile 5-FU data doses, dosing schedules and life-threatening for both well from literature. Furthermore, steady-state concentrations calculated additional set found literature AUCs non-life-threatening toxicity. Results: The model predictions matched with experimental data, confirming suitability model. Life-threatening was related above 6 mg/L, whereas low at less than 3 mg/L but steeply increased between 4 mg/L. Data analysis supported by decision algorithm suggests that better predictor AUC. Conclusions: recommend one hour starts about 50% steady state reached patients whom higher doses are clinically considered relevant. Monitoring starting has advantage dose correction could be made early before can observed.

Language: Английский

---

Circadian rhythms and cancer: implications for timing in therapy

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 18, 2024

Circadian rhythms, intrinsic cycles spanning approximately 24 h, regulate numerous physiological processes, including sleep–wake cycles, hormone release, and metabolism. These rhythms are orchestrated by the circadian clock, primarily located in suprachiasmatic nucleus (SCN) of hypothalamus. Disruptions whether due to genetic mutations, environmental factors, or lifestyle choices, can significantly impact health, contributing disorders such as sleep disturbances, metabolic syndrome, cardiovascular diseases. Additionally, there is a profound link between disruption development various cancer, influence on disease incidence progression. This incurred regulation clock pathways has its implication tumorigenesis, cell cycle control, DNA damage response, apoptosis, Furthermore, timing system modulates efficacy toxicity cancer treatments. In treatment, use chronotherapy optimize medical treatments, involves administering chemotherapy, radiation, other therapeutic interventions at specific intervals enhance minimize side effects. approach capitalizes variations cellular repair, progression, drug Preclinical clinical studies have demonstrated that improve index chemotherapeutic agents like cisplatin 5-fluorouracil enhancing anticancer activity reducing toxicity. Further research needed elucidate mechanisms underlying develop robust chronotherapeutic protocols tailored individual patients' profiles, potentially transforming care into more effective personalized treatment strategies.

Language: Английский

---

Circadian Rhythm Disruption in Cancer Survivors: From Oncogenesis to Quality of Life

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(20)

Published: Oct. 1, 2024

ABSTRACT Background Circadian rhythms are approximately 24‐hour cycles in physiological and behavioral processes. They entrained to the external solar day via blue wavelength light. Disruptions these intrinsic can lead circadian dysfunction, which has several negative implications on human health, including cancer development progression. Aims Here we review molecular mechanisms of disruption their impact tumor progression, discuss interplay between dysfunction basic scientific studies clinical data, propose potential data that may be used improve patient outcomes reduce cost treatment. Materials & Methods Using literature databases, relevant were analyzed draw overarching conclusions relationship rhythm dysruption cancer. Conclusions mediated by a number environmental factors such as exposure light at night, shift work, jetlag, social jetlag drive oncogenesis. Tumor growth well treatment, long‐term alterations negatively affect quality life survivors.

Language: Английский

---