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An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells.

ABSTRACT: Increasing evidence points to a role of the circadian clock in the regulation of cancer hallmarks with a strong impact on the understanding and treatment of this disease. Anti-cancer treatment can be personalized considering treatment timing. Here we present a new mathematical model based on data from three colorectal cancer cell lines and core-clock knock-outs, which couples the circadian and drug metabolism network, and that allows to determine toxicity profiles for a given drug and cell type. Moreover, this model integrates external Zeitgebers and thus may be used to fine-tune toxicity by using external factors, such as light, and therefore, to a certain extent, help fitting the endogenous rhythms of the patients to a defined clinic routine facilitating the implementation of time-dependent treatment in clinical practice.

SUBMITTER: Hesse J

PROVIDER: S-EPMC10290159 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells.

Hesse Janina J Müller Tim T Relógio Angela A

NPJ systems biology and applications 20230623 1

Increasing evidence points to a role of the circadian clock in the regulation of cancer hallmarks with a strong impact on the understanding and treatment of this disease. Anti-cancer treatment can be personalized considering treatment timing. Here we present a new mathematical model based on data from three colorectal cancer cell lines and core-clock knock-outs, which couples the circadian and drug metabolism network, and that allows to determine toxicity profiles for a given drug and cell type. ...[more]

PMID: 37353516

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Project description:BackgroundWhile specific elements of naturopathic medicine, such as botanical medicines and lifestyle interventions, have supporting evidence, there is limited quantitative data confirming its effectiveness as a comprehensive, whole-person medical approach for patients with metastatic colorectal cancer (CRC).ObjectiveThis study aims to retrospectively evaluate the integration of naturopathic modalities, including modulated electrohyperthermia (mEHT), into the standard of care for metastatic CRC. We compare survival outcomes between patients at the Integrated Health Clinic (IHC) and a matched control group from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, a de-identified, publicly available cancer registry in the United States.MethodsA retrospective chart review was conducted for 131 IHC patients diagnosed with stage IV CRC and treated with mEHT between 2010 and 2021. These patients were matched with 262 controls from the SEER database using propensity score matching. The primary outcome was overall survival, with time zero defined as the first IHC treatment date (with controls assigned the time zero of their matched IHC patient) to account for immortal time bias. Survival analysis was conducted using a Kaplan-Meier curve, log-rank test, and Cox proportional-hazards model.ResultsThe overall survival analysis did not achieve a statistically significant difference (HR = .76; 95% CI: .57-1.01) between the IHC (median survival time: 29 month) and SEER groups (median survival time: 18 months). Incorporating time-varying effects, the hazard ratio (HR) for the IHC group compared to the SEER group was .63 (95% CI: .46-.86) for survival <36 months, indicating a lower hazard of early mortality in the IHC group. Moreover, IHC patients who initiated treatment within 90 days of diagnosis had significantly improved survival compared to their matched controls (HR = .45; 95% CI: .28-.70).ConclusionThis study provides evidence that integrative naturopathic treatment, including mEHT, can significantly improve survival outcomes for CRC patients in the first 36 months post-treatment and when initiated within 90 days of diagnosis.

Dataset Information

An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells.

Publications

An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells.

Similar Datasets

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