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Cancers
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Novel Therapeutic Approaches for Cancer Treatment
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Novel Therapeutic Approaches for Cancer Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 8648

Special Issue Editor

Prof. Dr. Marzia Bruna Gariboldi

E-Mail Website
Guest Editor
Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
Interests: antineoplastic pharmacology; drug delivery; drug resistance; drug discovery; photodynamic therapy; tumor hypoxia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer affects a significant proportion of the global population and, according to the World Health Organization (WHO), is the second cause of death worldwide. Genetic and epigenetic alterations are among the most critical factors in the onset of carcinomas. Nevertheless, several lifestyle factors, such as physical inactivity, alcohol consumption, smoking, poor nutrition and exposure to ultraviolet radiation or X-rays, can contribute to the transition of healthy cells into malignant cells.

Conventional treatment approaches, such as surgery, chemotherapy and radiotherapy, are still in use, while significant advances are being made in various fields, including stem cell therapy, targeted therapy, ablation therapy, nanoparticles, natural antioxidants, photodynamic therapy, sonodynamic therapy, immunotherapy and ferroptosis-based therapy. However, to overcome the drawbacks associated with the strategies currently in use in the clinic, novel therapeutic options are needed. This has prompted the research of additional drugs and drug delivery strategies to offer more effective therapeutic alternatives.

This Special Issue aims at collecting original research articles and comprehensive reviews on the most recent advances concerning cancer treatment, such as, but not limited to, novel small anticancer molecules, epigenetic drugs, nanotechnology-based combination therapies, targeted therapies including external stimuli-activated approaches, drug repurposing and immunotherapeutic. 

Prof. Dr. Marzia Bruna Gariboldi
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 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. 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

  • cancer
  • small molecules
  • epigenetic drugs
  • drug delivery system
  • targeted therapy
  • personalized medicine
  • photodynamic therapy
  • photothermal therapy
  • sonodynamic therapy
  • drug repurposing
  • combination therapy

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Published Papers (6 papers)

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Research

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19 pages, 2320 KiB  
Article
In Vitro Evaluation of the Safety and Efficacy of Cibisatamab Using Adult Stem Cell-Derived Organoids and Colorectal Cancer Spheroids
by Victor Anstett, Elisa Heinzelmann, Francesco Piraino, Aline Roch, Antonius Chrisnandy, Maxim Norkin, Virginie Garnier, Krisztian Homicsko, Sylke Hoehnel-Ka and Nathalie Brandenberg
Cancers 2025, 17(2), 291; https://doi.org/10.3390/cancers17020291 - 17 Jan 2025
Viewed by 1220
Abstract
Objectives: Developing ex vivo models that replicate immune–tumor interactions with high fidelity is essential for advancing immunotherapy research, as traditional two-dimensional in vitro systems often lack the complexity required to fully represent these interactions. Methods: In this study, we establish a [...] Read more.
Objectives: Developing ex vivo models that replicate immune–tumor interactions with high fidelity is essential for advancing immunotherapy research, as traditional two-dimensional in vitro systems often lack the complexity required to fully represent these interactions. Methods: In this study, we establish a comprehensive 3D redirect lysis (3D-RDL) assay using colorectal cancer spheroids and adult stem cell-derived, healthy human organoids to evaluate the efficacy and safety profile of Cibisatamab, a bispecific antibody targeting carcinoembryonic antigens (CEAs) on cancer cells and CD3 on T cells. This model allows us to assess cytotoxic activity and immune responses, capturing variations in therapeutic response not observable in simpler systems. Our model integrates live imaging and cytotoxicity analyses to enable precise, real-time tracking of antibody effects on CEA-expressing tumor cells compared to healthy cells. Additionally, by standardizing effector-to-target cell ratios in each co-culture, we establish a reproducible workflow that enhances data accuracy and comparability across assays. Flow cytometry and Granzyme B release profiling further allow us to characterize immune cell activation, revealing distinct T cell activation markers and Granzyme B release patterns tied to Cibisatamab treatment. Results: Our results show that Cibisatamab effectively induces cell death in cancer spheroids with high CEA expression while being dose-dependent on target, off-tumor binding and killing on non-cancerous cells of healthy organoids with intermediate CEA levels. This highlights our model’s potential to predict clinical immunotherapy outcomes, capturing complex responses like immune activation, therapeutic selectivity, and potential resistance mechanisms. Conclusions: These findings underscore the utility of our model as a reliable, physiologically relevant tool for screening new immunotherapies and advancing our understanding of tumor-immune dynamics. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Cancer Treatment)
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13 pages, 4650 KiB  
Article
A Phthalimide-Functionalized Heptamethine Cyanine Dye for Tumor-Targeted Photothermal Therapy
by Yoonbin Park, Juhui Yang and Hoon Hyun
Cancers 2024, 16(24), 4155; https://doi.org/10.3390/cancers16244155 - 13 Dec 2024
Viewed by 701
Abstract
Background: A phthalimide-functionalized heptamethine cyanine dye, named Ph790H, is used for targeted photothermal cancer therapy in vivo. We highlight that the chemical structure of Ph790H is newly designed and synthesized for the first time in this study. Objectives: By possessing a rigid chloro-cyclohexenyl [...] Read more.
Background: A phthalimide-functionalized heptamethine cyanine dye, named Ph790H, is used for targeted photothermal cancer therapy in vivo. We highlight that the chemical structure of Ph790H is newly designed and synthesized for the first time in this study. Objectives: By possessing a rigid chloro-cyclohexenyl ring in the heptamethine cyanine backbone, the bifunctional near-infrared (NIR) fluorescent dye Ph790H can be preferentially accumulated in tumor without the need for additional targeting ligands, which is defined as the “structure-inherent tumor targeting” concept. Methods: The phototherapeutic effect of Ph790H is evaluated in HT-29 human colorectal cancer xenografts to be used as a cancer-targeting photothermal agent. Results: The results reveal that the Ph790H shows enhanced tumor accumulation in HT-29 xenografts 48 h post-injection with a high tumor-to-background ratio. After determination of the optimal timing for photothermal therapy (PTT), the HT-29 tumor-possessing nude mice pretreated with Ph790H are subsequently irradiated with an 808 nm NIR laser for 5 min. The tumor-targeted PTT treatment can efficiently inhibit the tumor development compared with that of control groups. Moreover, no tumor regrowth or Ph790H-induced mortality occurs after the treatment of Ph790H and laser irradiation during a period of monitoring. Conclusions: Therefore, this work demonstrates that the bifunctional phototheranostic agent Ph790H can be utilized for targeted cancer imaging and fluorescence-guided phototherapy simultaneously. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Cancer Treatment)
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12 pages, 3152 KiB  
Article
Evaluation of a Novel Lateral Emitting Laser Fiber for Near-Infrared Photoimmunotherapy
by Motofumi Suzuki, Hisataka Kobayashi and Hirofumi Hanaoka
Cancers 2024, 16(14), 2558; https://doi.org/10.3390/cancers16142558 - 17 Jul 2024
Viewed by 1670
Abstract
Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer therapy that uses NIR light and conjugates of a tumor-targeting monoclonal antibody and phthalocyanine dye. In clinical practice, frontal and cylindrical diffusers are the only options for NIR illumination. However, illumination in a narrow space is [...] Read more.
Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer therapy that uses NIR light and conjugates of a tumor-targeting monoclonal antibody and phthalocyanine dye. In clinical practice, frontal and cylindrical diffusers are the only options for NIR illumination. However, illumination in a narrow space is technically difficult with such diffusers. Therefore, we evaluated a lateral illumination system using a lateral emitting laser (LEL) fiber. The LEL fiber illuminated a certain area in a lateral direction. NIR-PIT with an LEL fiber reduced luciferase activity in a light-dose-dependent manner in A431-GFP-luc cells in vitro and significantly suppressed tumor proliferation in a xenograft mouse model. To evaluate the usefulness of the LEL fiber in the illumination of a narrow space, a tumor was illuminated from the inside of a cylinder, mimicking a narrow space, and the fluorescence intensity in the tumor was monitored. In the frontal diffuser, NIR light was unevenly delivered and little light reached a distal tumor area from the illuminated side. By contrast, the LEL fiber allowed a uniform illumination of the entire tumor, and a loss of fluorescence was observed even in distal areas. These findings suggested that the LEL fiber can be used for NIR-PIT and is suitable for NIR light illumination in a narrow space. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Cancer Treatment)
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Review

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24 pages, 5704 KiB  
Review
The Evolution of Anticancer 3D In Vitro Models: The Potential Role of Machine Learning and AI in the Next Generation of Animal-Free Experiments
by Carolina Momoli, Beatrice Costa, Lorenzo Lenti, Matilde Tubertini, Marco Daniele Parenti, Elisa Martella, Greta Varchi and Claudia Ferroni
Cancers 2025, 17(4), 700; https://doi.org/10.3390/cancers17040700 - 19 Feb 2025
Viewed by 414
Abstract
The development of anticancer therapies has increasingly relied on advanced 3D in vitro models, which more accurately mimic the tumor microenvironment compared to traditional 2D cultures. This review describes the evolution of these 3D models, highlighting significant advancements and their impact on cancer [...] Read more.
The development of anticancer therapies has increasingly relied on advanced 3D in vitro models, which more accurately mimic the tumor microenvironment compared to traditional 2D cultures. This review describes the evolution of these 3D models, highlighting significant advancements and their impact on cancer research. We discuss the integration of machine learning (ML) and artificial intelligence (AI) in enhancing the predictive power and efficiency of these models, potentially reducing the dependence on animal testing. ML and AI offer innovative approaches for analyzing complex data, optimizing experimental conditions, and predicting therapeutic outcomes with higher accuracy. By leveraging these technologies, the next generation of 3D in vitro models could revolutionize anticancer drug development, offering effective alternatives to animal experiments. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Cancer Treatment)
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29 pages, 2054 KiB  
Review
Green Tea Components: In Vitro and In Vivo Evidence for Their Anticancer Potential in Colon Cancer
by Federica Randisi, Gianpaolo Perletti, Emanuela Marras and Marzia Bruna Gariboldi
Cancers 2025, 17(4), 623; https://doi.org/10.3390/cancers17040623 - 13 Feb 2025
Viewed by 729
Abstract
Green tea consumption has been implicated in various biological activities, with particular emphasis on its anticancer properties. The antineoplastic effects of green tea are primarily attributed to its rich polyphenol content, among which, epigallocatechin-3-gallate (EGCG) is recognized as the most bioactive and potent [...] Read more.
Green tea consumption has been implicated in various biological activities, with particular emphasis on its anticancer properties. The antineoplastic effects of green tea are primarily attributed to its rich polyphenol content, among which, epigallocatechin-3-gallate (EGCG) is recognized as the most bioactive and potent catechin, responsible for the majority of its anticancer activity. This review provides a detailed examination of the in vitro and in vivo effects of green tea components, focusing on their potential therapeutic implications in colorectal cancer. The molecular mechanisms of action and bioactive constituents of green tea are systematically discussed, alongside an evaluation of experimental evidence supporting their efficacy. Furthermore, insights into the relationship between green tea dietary intake and colorectal cancer risk are analyzed, with a particular emphasis on clinical data and findings from meta-analyses involving patients diagnosed with colon cancer. The aggregated evidence underscores the necessity for well-designed randomized controlled trials and longitudinal cohort studies to substantiate the role of green tea as a chemopreventive agent. Additionally, future investigations should prioritize determining the optimal dosages, the appropriate durations of consumption, and the potential modulatory effects of dietary or lifestyle factors on green tea’s anticancer efficacy. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Cancer Treatment)
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45 pages, 18093 KiB  
Review
Dual-Action Therapeutics: DNA Alkylation and Antimicrobial Peptides for Cancer Therapy
by Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Elena Bustamante Munguira, Celia Andrés Juan and Eduardo Pérez-Lebeña
Cancers 2024, 16(18), 3123; https://doi.org/10.3390/cancers16183123 - 10 Sep 2024
Cited by 4 | Viewed by 2638
Abstract
Cancer remains one of the most difficult diseases to treat, requiring continuous research into innovative therapeutic strategies. Conventional treatments such as chemotherapy and radiotherapy are effective to a certain extent but often have significant side effects and carry the risk of resistance. In [...] Read more.
Cancer remains one of the most difficult diseases to treat, requiring continuous research into innovative therapeutic strategies. Conventional treatments such as chemotherapy and radiotherapy are effective to a certain extent but often have significant side effects and carry the risk of resistance. In recent years, the concept of dual-acting therapeutics has attracted considerable attention, particularly the combination of DNA alkylating agents and antimicrobial peptides. DNA alkylation, a well-known mechanism in cancer therapy, involves the attachment of alkyl groups to DNA, leading to DNA damage and subsequent cell death. Antimicrobial peptides, on the other hand, have been shown to be effective anticancer agents due to their ability to selectively disrupt cancer cell membranes and modulate immune responses. This review aims to explore the synergistic potential of these two therapeutic modalities. It examines their mechanisms of action, current research findings, and the promise they offer to improve the efficacy and specificity of cancer treatments. By combining the cytotoxic power of DNA alkylation with the unique properties of antimicrobial peptides, dual-action therapeutics may offer a new and more effective approach to fighting cancer. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Cancer Treatment)
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