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Design, Synthesis and Development of Anticancer Drugs Targeting the Tumor Microenvironment

A Special Issue of International Journal of Molecular Sciences (ISSN 1422-0067) belonging to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 760

Editor


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Guest Editor
Development of Hypoxic Cell Radiosensitizers, Tokushima University, Tokushima, Japan
Interests: tumour biology; tumour cell culture

Special Issue Information

Dear Colleagues,

Malignant tumors (cancer) have long been the leading cause of death in Japan and are also among the primary causes of mortality in other developed countries. Consequently, there is a persistent and growing need for excellent cancer treatments. In recent years, the development of anticancer drugs has increased significantly, with a large proportion of new therapeutic development focused on oncology.

Cancer is not composed solely of tumor cells; it develops through complex interactions with fibroblasts (cancer-associated fibroblast—CAF), endothelial cells (tumor endothelial cells—TECs), and immune cells (tumor-associated macrophage—TAMs). Therefore, it is difficult to eradicate cancer with drugs that target only tumor cells. There is a strong need for drugs that modulate the tumor microenvironment, including angiogenic inhibitors, anti-metastatic agents, hypoxic cytotoxins, and immunostimulants, as well as agents that enhance physicochemical therapies, such as radiosensitizers and ultrasound sensitizers.

Furthermore, in vivo models that accurately reproduce the tumor microenvironment are essential for screening these therapies. Chicken eggs offer an ideal alternative animal model, enabling the simple and rapid creation of a large number of tumor-bearing models.

This Special Issue welcomes a broad range of research and development focused on anticancer drugs that target the tumor microenvironment.

Prof. Dr. Yoshihiro Uto
Guest Editor

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Keywords

  • anticancer drugs
  • tumor microenvironment
  • in vivo model
  • cancer-associated fibroblast
  • tumor-associated macrophage
  • tumor hypoxia
  • tumor endothelial cells

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Published Papers (1 paper)

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Research

17 pages, 15351 KB  
Article
First-in-Class Immuno-Oncology Drug APG157DS Repolarizes Innate Immune Cells and Induces Durable Remission in a Syngeneic Glioblastoma Model
by Shubhasmita Mohapatra, Adrian Guerrero, Neha Rahman, Stefan Markovic, Lauren O’Donnell, Youssef Zaim Wadghiri, Khondoker Takia Zaman, Luis Avila, Parag Mehta and Probal Banerjee
Int. J. Mol. Sci. 2026, 27(15), 6687; https://doi.org/10.3390/ijms27156687 - 27 Jul 2026
Viewed by 433
Abstract
APG157DS is a multi-component investigational drug which is currently the subject of multiple cancer trials. It has shown promising efficacy in patients with head and neck cancer. We report its immuno-modulatory effect in a syngeneic mouse model of glioblastoma (GBM). Long-term treatment with [...] Read more.
APG157DS is a multi-component investigational drug which is currently the subject of multiple cancer trials. It has shown promising efficacy in patients with head and neck cancer. We report its immuno-modulatory effect in a syngeneic mouse model of glioblastoma (GBM). Long-term treatment with APG157DS led to durable tumor remission in 50% of mice, while all vehicle-treated mice reached humane endpoints within 42 days. Mechanistically, the drug induced selective repolarization of tumor-associated macrophages (TAMs) from an immunosuppressive Arg1high/iNOSlow phenotype to a tumoricidal Arg1low/iNOShigh state, accompanied by increased intratumoral recruitment of activated (NKp46+) natural killer cells and CD8+ cytotoxic T-cells. APG157DS also suppressed vascular endothelial growth factor (VEGF) and Hypoxia-inducible factor 1-alpha (HIF-1α) expression in tumors, further impairing tumor growth. Notably, APG157DS did not elicit off-target macrophage activation in peripheral tissues such as the spleen, highlighting its selective immune targeting. These findings provide a mechanistic rationale for further clinical development of APG157DS in GBM and potentially other immune-evasive cancers. Full article
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