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From Metronomic Chemotherapy to Time-Optimized Cancer Treatments

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 31 October 2026 | Viewed by 488

Editor


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Guest Editor
Department of Oncology, Jagiellonian University Medical College, 31-007 Cracow, Poland
Interests: metronomic chemotherapy; geriatric oncology; combined treatment modalities; novel therapeutic targets; breast cancer; ovarian cancer; prostate cancer; RCC; urothelial cancer
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Special Issue Information

Dear Colleagues,

The concept of time is gaining prominence as a crucial factor influencing the effectiveness, safety, and overall biological impact of cancer treatments. While oncology has traditionally emphasized drug selection and dosage in defining treatment intensity, recent insights underscore the importance of timing and scheduling therapies. Variations in the timing of drug delivery—ranging from continuous low-dose administration to structured, intermittent protocols—have been shown to significantly affect clinical outcomes.

In chemotherapy, the timing of drug administration has long been considered important. Conventional cyclical regimens are designed to balance tumor suppression with healthy tissue recovery. In contrast, metronomic chemotherapy involves frequent administration of low drug doses, aiming to sustain anticancer activity while minimizing toxicity. This strategy can promote anti-angiogenic effects and modulate immune responses. This Special Issue delves into how timing adjustments in chemotherapy can influence tumor progression, side-effect profiles, resistance development, and interactions between tumor and host systems.

Radiotherapy also relies heavily on temporal precision. Treatment variables such as fractionation schedules, treatment intensity, and accelerated protocols can alter how tumors and normal tissues respond to radiation. Articles in this issue will examine the biological and clinical rationale for personalized, time-sensitive radiotherapy strategies, including hypofractionation, adaptive radiotherapy, and high-frequency regimens.

In the field of immunotherapy, timing is increasingly recognized as a key consideration. Extended dosing intervals for immune checkpoint inhibitors, supported by a better understanding of their prolonged immune effects and pharmacokinetics, are allowing for less frequent dosing without compromising therapeutic outcomes. These findings challenge conventional scheduling models and pave the way for more individualized and resource-efficient immunotherapy practices.

Additionally, this Special Issue will feature studies on pharmacokinetics, pharmacodynamics, drug metabolism, and time-dependent treatment responses across various therapeutic modalities. Together, these contributions offer a comprehensive overview of how strategic timing of cancer therapies—including chemotherapy, radiotherapy, immunotherapy, and targeted treatments—can lead to more effective, patient-centered cancer care.

Prof. Dr. Piotr J. Wysocki
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metronomic chemotherapy
  • time-dependent treatment
  • chemotherapy
  • immunotherapy
  • pharmacokinetics
  • pharmacodynamics

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Published Papers (1 paper)

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Review

28 pages, 535 KB  
Review
Predictive Biomarkers of Metronomic Chemotherapy Response in Solid Tumors: Chasing an Elusive Signal
by Piotr Jan Wysocki, Łukasz Kwinta and Ewa Wysocka
Cancers 2026, 18(15), 2488; https://doi.org/10.3390/cancers18152488 - 3 Aug 2026
Viewed by 291
Abstract
Background: Metronomic chemotherapy (MCT), understood as continuous, low-dose cytotoxic administration without prolonged drug-free intervals, has become an established strategy in several solid tumors, acting primarily through antiangiogenic, immunomodulatory, and direct cytostatic mechanisms rather than replication-dependent cytotoxicity. Despite an expanding evidence base, including positive [...] Read more.
Background: Metronomic chemotherapy (MCT), understood as continuous, low-dose cytotoxic administration without prolonged drug-free intervals, has become an established strategy in several solid tumors, acting primarily through antiangiogenic, immunomodulatory, and direct cytostatic mechanisms rather than replication-dependent cytotoxicity. Despite an expanding evidence base, including positive randomized trials, validated predictive biomarkers of response remain unavailable. Methods: We searched PubMed/MEDLINE, Embase, and ClinicalTrials.gov (January 2000 to July 2026) for phase II/III randomized trials, prospective cohorts, and selected retrospective analyses of MCT in breast cancer, head and neck squamous cell carcinoma, NSCLC, and mCRC, and extracted biomarker data from embedded translational substudies of eligible trials. Results: In breast cancer, phase III SYSUCC-001 (adjuvant metronomic capecitabine, improved DFS in TNBC) and MECCA (metronomic capecitabine plus aromatase inhibitor in HR+/HER2− disease) provide the strongest evidence, supported by randomized phase II data for the VEX regimen (METEORA-II) and MCT-anti-PD-1 combinations. TEMPO LUNG established metronomic vinorelbine as effective in platinum-unfit NSCLC, while CAIRO3 confirmed metronomic capecitabine–bevacizumab as an effective mCRC maintenance therapy. Most recently, the phase III TMC-I trial extended positive randomized evidence to head and neck cancer. Candidate biomarkers span angiogenic, immune, tumor proliferative, molecular, pharmacodynamic cytokine, on-treatment clinical (adverse-event-based), and gut–microbiome domains, with FOXC1, circulating endothelial cell kinetics, VEGF pathway markers, and regulatory T-cell dynamics among the most promising; however, none has been prospectively validated in a dedicated confirmatory trial. Conclusions: MCT has moved from empirical use to an evidence-based strategy across multiple tumor types, but the lack of validated predictive biomarkers limits informed patient selection. Future trials should incorporate biomarker-driven designs, particularly FOXC1, endothelial cell kinetics, and immune profiling as co-primary objectives. Defining an MCT-sensitive biological phenotype remains the key translational challenge for the field. Full article
(This article belongs to the Special Issue From Metronomic Chemotherapy to Time-Optimized Cancer Treatments)
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