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Treatment-Induced Metabolic and Inflammatory Responses in Cancer

A Special Issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 15 December 2026 | Viewed by 1100

Editor

1. Department of Radiation Oncology, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA
2. Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Interests: lipid metabolism; cellular stress responses; oxidative stress; radiation-induced normal tissue toxicity; chemotherapy-induced nephrotoxicity; cancer biology; tumor microenvironment; DNA damage response; inflammation; salivary gland toxicity; kidney injury; radiobiology; nanomedicine; biomarkers of tissue injury; therapeutic strategies to reduce cancer treatment-related toxicities
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Special Issue Information

Dear Colleagues,

Radiation therapy, including external beam and internal radionuclide approaches, together with chemotherapy and immunotherapy, forms the cornerstone of contemporary cancer control. Despite substantial advances in treatment delivery and systemic therapies, long-term outcomes are frequently limited by normal tissue toxicity, chronic inflammation, metabolic reprogramming, and the emergence of therapeutic resistance. Growing evidence highlights lipid dysregulation and inflammatory signaling as central mediators linking tumor response, immune modulation, and organ-specific injury across cancers.

This Special Issue aims to provide a comprehensive forum for basic, translational, and clinical studies examining the biological consequences of multimodal cancer therapies. We welcome contributions that explore mechanisms of cancer control, treatment-induced metabolic and inflammatory alterations, and normal tissue injury following radiation, chemotherapy, and immunotherapy. By integrating molecular insights with preclinical and clinical observations, this Special Issue aims to advance strategies that enhance therapeutic efficacy while mitigating toxicity and improving long-term patient outcomes.

This Special Issue welcomes reviews as well as original research articles, which should be submitted by 15 December 2026.

Dr. Anis Ahmad
Guest Editor

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Keywords

  • radiation therapy
  • chemotherapy
  • immunotherapy
  • normal tissue toxicity
  • metabolic reprogramming
  • chronic inflammation
  • lipid dysregulation
  • treatment resistance
  • inflammatory signaling

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Published Papers (1 paper)

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Research

18 pages, 2059 KB  
Article
Multi-Omics Analysis Reveals Chronic Cisplatin Exposure Is Associated with Metabolic Rewiring Toward Glutathione Metabolism to Support Redox Adaptation in High-Grade Serous Ovarian Cancer
by Ashlyn Conant, Kayla Sanchez, Shreya Patil, Ethan Nyein, Tise Suzuki, Gary Yu, Marlon Maus, Salvador Soriano, Christian Hurtz and Juli J. Unternaehrer
Cancers 2026, 18(12), 1945; https://doi.org/10.3390/cancers18121945 - 15 Jun 2026
Viewed by 745
Abstract
Background: Platinum-based chemotherapy is the frontline treatment for high-grade serous ovarian cancer (HGSOC); however, the development of therapy resistance greatly limits clinical response. Increasing evidence suggests that platinum agent-driven metabolic programming, particularly within redox-associated pathways, may contribute to chemoresistance. Methods: A syngeneic pair [...] Read more.
Background: Platinum-based chemotherapy is the frontline treatment for high-grade serous ovarian cancer (HGSOC); however, the development of therapy resistance greatly limits clinical response. Increasing evidence suggests that platinum agent-driven metabolic programming, particularly within redox-associated pathways, may contribute to chemoresistance. Methods: A syngeneic pair of patient-derived HGSOC cell lines representing cisplatin-sensitive (SE) and cisplatin-resistant (CR) states were evaluated using a multi-omics approach. Differential metabolite abundance and gene expression were assessed, followed by gene set and pathway enrichment analyses to identify coordinated metabolic shifts. In silico analysis of an additional sensitive and resistant HGSOC cell line validated the glutathione pathway upregulation seen in the patient-derived model. The functional contribution of the glutathione pathway on cisplatin resistance was evaluated following glutathione inhibition. Results: Chronic cisplatin exposure induced extensive metabolic rewiring in CR cells, characterized by enrichment of glutathione metabolism at both the metabolite and gene levels. Increased reduced glutathione was observed alongside upregulation of key enzymes involved in its de novo biosynthesis, recycling, and utilization, consistent with enhanced detoxification capacity relating to cisplatin-induced oxidative stress. Additionally, taurine was highly enriched, further highlighting a metabolic shift towards enhanced antioxidant mechanisms. CR cells also demonstrated an increase in NADPH-generating pathways, including amino acid metabolism and fatty acid β oxidation, to support redox balance and biosynthetic demands of increased glutathione metabolism. Transcriptional remodeling of the γ-glutamyl cycle further indicated a shift toward increased glutathione turnover, suggesting that the coordinated changes seen may define a metabolic state enhanced in oxidative stress tolerance and therapeutic resistance. These transcriptional changes were also seen in another model of platinum sensitivity/resistance, indicating a conserved response associated with platinum-induced resistance. Finally, concurrent cisplatin treatment and glutathione inhibition significantly increased sensitivity within the CR cells. Conclusions: These findings suggest that cisplatin-resistant cells, previously exposed to a platinum-based agent, may undergo distinct metabolic rewiring towards antioxidant pathways to survive chronic chemotherapeutic stress. Targeting components of these systems may represent a viable strategy to overcome platinum resistance and improve therapeutic outcomes. Full article
(This article belongs to the Special Issue Treatment-Induced Metabolic and Inflammatory Responses in Cancer)
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