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Natural Compounds in Cancer Therapy: Molecular Mechanisms and Translational Potential
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Natural Compounds in Cancer Therapy: Molecular Mechanisms and Translational Potential

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 702

Special Issue Editor

Dr. Gregory Christodoulidis

E-Mail Website
Guest Editor
Department of General Surgery, General University Hospital of Larissa, Mezourlo, 41110 Larissa, Greece
Interests: proto-oncogenes; oncogenes; gastrointestinal cancer; biomarkers; antitumor agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The integration of natural compounds into cancer research has opened new avenues for therapeutic innovation. Derived from a variety of natural sources—including plants, fungi, marine organisms, and microorganisms—these bioactive molecules have demonstrated a wide range of anticancer properties, often with reduced toxicity compared to conventional chemotherapeutics. Their ability to modulate diverse molecular pathways involved in carcinogenesis, such as oxidative stress, inflammation, apoptosis, cell cycle regulation, angiogenesis, and metastasis, positions them as promising agents for both cancer prevention and treatment.

This Special Issue aims to synthesize cutting-edge research and comprehensive reviews exploring the molecular basis and translational relevance of natural compounds in oncology. We invite submissions that investigate the mechanisms of action of these compounds in various cancer models, as well as studies focusing on novel delivery systems, bioavailability enhancement, synergistic effects with standard therapies, and resistance modulation. Additionally, we encourage research exploring the use of natural compounds as adjuvants, immune modulators, or targeted agents in precision medicine. By assembling diverse perspectives from molecular biology, pharmacology, oncology, and natural product chemistry, this Special Issue aims to advance our understanding of how nature-derived molecules can contribute to the next generation of cancer therapies.

Dr. Gregory Christodoulidis
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 short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • natural compounds
  • cancer research
  • oxidative stress

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Published Papers (1 paper)

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Review

35 pages, 1216 KiB  
Review
Modulation of Endoplasmic Reticulum Stress in Experimental Anti-Cancer Therapy
by Natalia Ivanovna Agalakova
Int. J. Mol. Sci. 2025, 26(13), 6407; https://doi.org/10.3390/ijms26136407 - 3 Jul 2025
Viewed by 588
Abstract
The growth of tumor cells is accompanied by an increased rate of endoplasmic reticulum stress (ERS), the accumulation of misfolded proteins, and the activation of a network of adaptive signaling pathways known as the unfolded protein response (UPR). Although the UPR is an [...] Read more.
The growth of tumor cells is accompanied by an increased rate of endoplasmic reticulum stress (ERS), the accumulation of misfolded proteins, and the activation of a network of adaptive signaling pathways known as the unfolded protein response (UPR). Although the UPR is an adaptive reaction aiming to restore ER proteostasis, prolonged and severe ERS leads to cell death. Taking into account that the components of the ERS/UPR machinery in cancers of different types can be overexpressed or downregulated, both the induction of excessive ERS and suppression of UPR have been proposed as therapeutic strategies to sensitize cells to conventional chemotherapy. This narrative review presents a several examples of using natural and synthetic compounds that can either induce persistent ERS by selectively blocking ER Ca2+ pumps (SERCA) to disrupt ER Ca2+ homeostasis, or altering the activity of UPR chaperones and sensors (GRP78, PERK, IRE1α, and ATF6) to impair protein degradation signaling. The molecular alterations induced by miscellaneous inhibitors of ERS/UPR effectors are described as well. These agents showed promising therapeutic effects as a part of combination therapy in preclinical experimental settings; however, the number of clinical trials is still limited, while their results are inconsistent. Multiple side effects, high toxicity to normal cells, or poor bioavailability also hampers their clinical application. Since the pharmacological modulation of ERS/UPR is a valuable approach to sensitize cancer cells to standard chemotherapy, the search for more selective agents with better stability and low toxicity, as well as the development of more efficient delivery systems that can increase their therapeutic specificity, are highly required goals for future studies. Full article
(This article belongs to the Special Issue Natural Compounds in Cancer Therapy: Molecular Mechanisms and Translational Potential)
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