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Novel Combination Therapies for the Solid Cancers Treatment
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Novel Combination Therapies for the Solid Cancers Treatment

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 1967

Special Issue Editor

Dr. Anne Mary Noonan

E-Mail Website
Guest Editor
Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA
Interests: gastrointestinal cancers; drug development; hepatocellular carcinoma; pancreatic adenocarcinoma; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The treatment of solid cancers, which encompass a diverse array of malignancies including breast, lung, prostate, and colorectal cancers, remains a formidable challenge in oncology. Despite significant advances in early detection, surgical techniques, and conventional therapies such as chemotherapy and radiation, the limitations of these approaches often necessitate the exploration of novel strategies to enhance therapeutic efficacy and overcome resistance.

Recent advancements in molecular biology and genomics have elucidated the complex and heterogeneous nature of solid tumors, revealing a landscape characterized by genetic mutations, epigenetic alterations, and a dynamic tumor microenvironment. This complexity has underscored the need for innovative therapeutic paradigms that integrate multiple modalities to target various aspects of tumor biology.

In response to this need, novel combination therapies have emerged as a promising strategy to improve treatment outcomes for solid cancers. These approaches involve the synergistic use of different therapeutic agents or modalities, such as targeted therapies, immunotherapies, and novel small molecules, with the aim of enhancing efficacy, minimizing resistance, and reducing toxicity. The rationale behind combination therapies lies in their potential to address multiple mechanisms of resistance simultaneously, exploit complementary mechanisms of action, and provide a more comprehensive treatment of tumors.

This Special Issue seeks to provide an overview of the current state of research on novel combination therapies for solid cancers. It will examine the underlying principles of combination therapy and highlight recent advancements. By exploring the integration of emerging therapies and the strategic design of combination regimens, this discussion aims to shed light on how these innovative strategies could reshape the future of cancer treatment and ultimately improve patient outcomes.

Dr. Anne Mary Noonan
Guest Editor

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Keywords

  • solid cancer
  • breast cancer
  • lung cancer
  • prostate cancer
  • colorectal cancer
  • therapeutic efficacy
  • drug resistance
  • genetic mutation
  • tumor microenvironment
  • immunotherapies
  • novel combination therapies

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Published Papers (3 papers)

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Research

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16 pages, 3675 KiB  
Article
Targeting Heat Shock Transcription Factor 4 Enhances the Efficacy of Cabozantinib and Immune Checkpoint Inhibitors in Renal Cell Carcinoma
by Saeki Saito, Hirofumi Yoshino, Seiya Yokoyama, Mitsuhiko Tominaga, Gang Li, Junya Arima, Ichiro Kawahara, Ikumi Fukuda, Akihiko Mitsuke, Takashi Sakaguchi, Satoru Inoguchi, Ryosuke Matsushita, Yasutoshi Yamada, Shuichi Tatarano, Akihide Tanimoto and Hideki Enokida
Int. J. Mol. Sci. 2025, 26(4), 1776; https://doi.org/10.3390/ijms26041776 - 19 Feb 2025
Viewed by 601
Abstract
Recently, immune checkpoint inhibitors (ICIs) and cabozantinib, a tyrosine kinase inhibitor (TKI), have been used to treat renal cell carcinoma (RCC); the combination of these agents has become a standard treatment for RCC. TKIs generally target vascular endothelial growth factor. However, cabozantinib is [...] Read more.
Recently, immune checkpoint inhibitors (ICIs) and cabozantinib, a tyrosine kinase inhibitor (TKI), have been used to treat renal cell carcinoma (RCC); the combination of these agents has become a standard treatment for RCC. TKIs generally target vascular endothelial growth factor. However, cabozantinib is characterized by its targeting of MET. Therefore, cabozantinib can be used as a late-line therapy for TKI-resistant RCC. According to data from The Cancer Genome Atlas (TCGA), heat shock transcription factor 4 (HSF4) expression is higher in RCC tissues than in normal renal tissues. HSF4 binds to the MET promoter in colorectal carcinoma to enhance MET expression and promote tumor progression. However, the functional role of HSF4 in RCC is unclear. We performed loss-of-function assays of HSF4, and our results showed that HSF4 knockdown in RCC cells significantly decreased cell functions. Moreover, MET expression was decreased in HSF4-knockdown cells but elevated in sunitinib-resistant RCC cells. The combination of cabozantinib and HSF4 knockdown reduced cell proliferation in sunitinib-resistant cells more than each monotherapy alone. Furthermore, HSF4 knockdown combined with an ICI showed synergistic suppression of tumor growth in vivo. Overall, our strategy involving HSF4 knockdown may enhance the efficacy of existing therapies, such as cabozantinib and ICIs. Full article
(This article belongs to the Special Issue Novel Combination Therapies for the Solid Cancers Treatment)
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Review

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42 pages, 1190 KiB  
Review
The Role of microRNAs in Lung Cancer: Mechanisms, Diagnostics and Therapeutic Potential
by Elżbieta Bartoszewska, Piotr Misiąg, Melania Czapla, Katarzyna Rakoczy, Paulina Tomecka, Michał Filipski, Elżbieta Wawrzyniak-Dzierżek and Anna Choromańska
Int. J. Mol. Sci. 2025, 26(8), 3736; https://doi.org/10.3390/ijms26083736 - 15 Apr 2025
Viewed by 82
Abstract
MicroRNAs (miRNAs) are small RNA molecules that do not have coding functions but play essential roles in various biological processes. In lung cancer, miRNAs affect the processes of tumor initiation, progression, metastasis, and resistance to treatment by regulating gene expression. Tumor-suppressive miRNAs inhibit [...] Read more.
MicroRNAs (miRNAs) are small RNA molecules that do not have coding functions but play essential roles in various biological processes. In lung cancer, miRNAs affect the processes of tumor initiation, progression, metastasis, and resistance to treatment by regulating gene expression. Tumor-suppressive miRNAs inhibit oncogenic pathways, while oncogenic miRNAs, known as oncomiRs, promote malignant transformation and tumor growth. These dual roles position miRNAs as critical players in lung cancer biology. Studies in recent years have shown the significant potential of miRNAs as both prognostic and diagnostic biomarkers. Circulating miRNAs in plasma or sputum demonstrate specificity and sensitivity in detecting early-stage lung cancer. Liquid biopsy-based miRNA panels distinguish malignant from benign lesions, and specific miRNA expression patterns correlate with disease progression, response to treatment, and overall survival. Therapeutically, miRNAs hold promise for targeted interventions. Strategies such as miRNA replacement therapy using mimics for tumor-suppressive miRNAs and inhibition of oncomiRs with antagomiRs or miRNA sponges have shown preclinical success. Key miRNAs, including the let-7 family, miR-34a, and miR-21, are under investigation for their therapeutic potential. It should be emphasized that delivery difficulties, side effects, and limited stability of therapeutic miRNA molecules remain obstacles to their clinical use. This article examines the roles of miRNAs in lung cancer by indicating their mechanisms of action, diagnostic significance, and therapeutic potential. By addressing current limitations, miRNA-based approaches could revolutionize lung cancer management, offering precise, personalized, and minimally invasive solutions for diagnosis and treatment. Full article
(This article belongs to the Special Issue Novel Combination Therapies for the Solid Cancers Treatment)
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16 pages, 1691 KiB  
Review
Microenvironmental Drivers of Glioma Progression
by Hyun Ji Jang and Jong-Whi Park
Int. J. Mol. Sci. 2025, 26(5), 2108; https://doi.org/10.3390/ijms26052108 - 27 Feb 2025
Viewed by 595
Abstract
Gliomas, particularly glioblastoma (GBM), are among the most challenging brain tumors due to their complex and dynamic tumor microenvironment (TME). The TME plays a pivotal role in tumor progression, immune evasion, and resistance to therapy through intricate interactions among glioma cells, immune components, [...] Read more.
Gliomas, particularly glioblastoma (GBM), are among the most challenging brain tumors due to their complex and dynamic tumor microenvironment (TME). The TME plays a pivotal role in tumor progression, immune evasion, and resistance to therapy through intricate interactions among glioma cells, immune components, neurons, astrocytes, the extracellular matrix, and the blood-brain barrier. Targeting the TME has demonstrated potential, with immunotherapies such as checkpoint inhibitors and neoadjuvant therapies enhancing immune responses. Nonetheless, overcoming the immunosuppressive landscape and metabolic adaptations continues to pose significant challenges. This review explores the diverse cellular and molecular mechanisms that shape the glioma TME. A deeper understanding of these mechanisms holds promise for providing novel therapeutic opportunities to improve glioma treatment outcomes. Full article
(This article belongs to the Special Issue Novel Combination Therapies for the Solid Cancers Treatment)
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