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The Development of Effective Therapy Targeting the Microenvironment of Cancer (2nd Edition)

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

Deadline for manuscript submissions: 30 September 2026 | Viewed by 2956

Special Issue Editors


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Guest Editor
Graduate School of Agricultural and Life Science, University of Tokyo, Tokyo 113-8657, Japan
Interests: cancer treatment; experimental pathology; regenerative medicine
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Tokyo, Japan
Interests: breast cancer; hboc; breast cancer

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous one, entitled "The Development of Effective Therapy Targeting the Microenvironment of Cancer”.

For many years, cancer medications have primarily targeted the inhibition of cancer cell growth. However, over the past 20 years, the mechanisms that form the tumor microenvironment through interactions with the stromal cells surrounding cancer cells have been elucidated. These cancer stromal cells are involved in the proliferation, invasion, and metastasis of cancer cells, even though they are normal cells. Therefore, therapeutic approaches targeting the tumor microenvironment have recently attracted much attention. In this Special Issue, we are seeking papers on innovative therapies targeting the tumor microenvironment. Proposals for any type of therapy, e.g., chemotherapy, antibody therapy, radiation therapy, etc., will be accepted. However, it is preferable that the results be proven to be effective at the animal level, rather than in a culture system.

Prof. Dr. Moriaki Kusakabe
Dr. Kanae Taruno
Guest Editors

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-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
  • tumor microenvironment
  • cancer therapy
  • cancer cell
  • animal level

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Published Papers (2 papers)

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Review

21 pages, 1808 KB  
Review
Targeting the Tumor Microenvironment in Triple-Negative Breast Cancer: Emerging Roles of Monoclonal Antibodies and Immune Modulation
by Stephanie Figueroa, Niradiz Reyes, Raj K. Tiwari and Jan Geliebter
Cancers 2026, 18(3), 412; https://doi.org/10.3390/cancers18030412 - 28 Jan 2026
Viewed by 1362
Abstract
Triple-negative breast cancer (TNBC) is an aggressive and clinically challenging subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. This molecular phenotype narrows the availability of targeted therapies and contributes to high rates of early relapse, [...] Read more.
Triple-negative breast cancer (TNBC) is an aggressive and clinically challenging subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. This molecular phenotype narrows the availability of targeted therapies and contributes to high rates of early relapse, therapeutic resistance, and poor clinical outcomes. Mounting evidence pinpoints the tumor microenvironment (TME) as a central driver of TNBC progression, immune evasion, and resistance to treatment. The TME encompasses a complex and dynamic network of immune and stromal cells, extracellular matrix components, and soluble mediators that collectively shape tumor behavior and influence therapeutic response. Notably, TNBC often displays an immunologically active microenvironment, marked by high levels of tumor-infiltrating lymphocytes and immune checkpoint expression, opening a window for immune-based therapeutic strategies. This narrative review summarizes current knowledge on the cellular, molecular, and structural features of the TNBC tumor microenvironment, with particular focus on immunosuppressive mechanisms mediated by tumor-associated macrophages, myeloid-derived suppressor cells, cancer-associated fibroblasts, and dysfunctional T cells. We describe the clinical development and therapeutic impact of monoclonal antibodies, including immune checkpoint inhibitors and antibody–drug conjugates. Additionally, we discuss strategies aimed at modulating the TME to enhance monoclonal antibody efficacy, including immune cell reprogramming, extracellular matrix remodeling, cytokine/chemokine blockade, and combination treatment strategies. Finally, we highlight the role of biomarker-driven patient stratification and personalized therapeutic strategies, addressing current challenges and future directions in TME-targeted drug development. Together, these insights underscore the potential of integrating immune modulation and monoclonal antibody-based therapies to improve outcomes for TNBC patients. Full article
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24 pages, 4823 KB  
Review
Exosome-Enhanced Sonodynamic Therapy in Cancer: Emerging Synergies and Modulation of the Tumor Microenvironment
by Giulia Chiabotto, Marzia Conte and Valentina Cauda
Cancers 2026, 18(1), 118; https://doi.org/10.3390/cancers18010118 - 30 Dec 2025
Viewed by 1283
Abstract
The development of safer, more effective, and tumor-specific therapeutic strategies remains a major challenge in oncology. Conventional treatments such as chemotherapy and radiotherapy often cause severe side effects and are limited in their ability to target deep-seated or resistant tumors. In this context, [...] Read more.
The development of safer, more effective, and tumor-specific therapeutic strategies remains a major challenge in oncology. Conventional treatments such as chemotherapy and radiotherapy often cause severe side effects and are limited in their ability to target deep-seated or resistant tumors. In this context, sonodynamic therapy (SDT) has emerged as a promising, non-invasive option, harnessing low-intensity ultrasound to activate sonosensitizers deep within tissues and generate cytotoxic reactive oxygen species (ROS) that selectively induce cancer cell death. Interestingly, SDT can also be combined with other therapies to achieve synergistic effects. However, despite encouraging preclinical results, SDT clinical translation is hindered by the poor aqueous solubility, instability, and low tumor specificity of traditional sonosensitizers. To overcome these limitations, recent studies have focused on employing extracellular vesicles (EVs), especially exosomes, as natural, biomimetic nanocarriers for sonosensitizer delivery. EVs offer unique advantages, including high biocompatibility, low immunogenicity, and intrinsic tumor-targeting ability, which make them ideal platforms for improving the therapeutic precision of SDT. Although several delivery strategies have been proposed, a comprehensive and focused overview of approaches specifically designed to enhance SDT performance using EVs is currently lacking. This review summarizes recent advances in integrating EVs with SDT for cancer treatment. It discusses the mechanisms underlying SDT, the engineering strategies developed to enhance exosome functionality, and the synergistic effects achieved through this combination. Furthermore, this review emphasizes that EV-based SDT not only enhances tumor accumulation of the therapeutic nanoplatforms, but also actively remodels the tumor microenvironment by improving oxygen availability, reversing immunosuppressive conditions, and triggering durable antitumor responses. Finally, the review addresses the translational challenges and outlines the critical future directions required to advance this promising therapeutic approach toward clinical application. Full article
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