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Medicina
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Updates on the Changing Landscape of Immunotherapy and Targeted Therapy...
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Updates on the Changing Landscape of Immunotherapy and Targeted Therapy in Cancer

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 2158

Special Issue Editors

Prof. Dr. Monica Neagu

E-Mail Website1 Website2
Guest Editor
“Victor Babeș” National Institute of Pathology, 99-101 Spl. Independentei, 050096 Bucharest, Romania
Interests: immunology; biomarkers; skin pathology
Special Issues, Collections and Topics in MDPI journals
Dr. Gheorghita Isvoranu

E-Mail Website
Guest Editor Assistant
“Victor Babeș” National Institute of Pathology, 99-101 Spl. Independentei, 050096 Bucharest, Romania
Interests: immunity; immunotherapy; oncology; inflammation; experimental animal models

Special Issue Information

Dear Colleagues,

Cancer is a multifaceted process that involves various mechanisms in a complex pathological network connecting myriads of cellular events. In solid tumors, within the tumor niche, inflammation and oxidative stress, to highlight just two important processes, shape cellular responses, whether the tumor cell itself or the immune cells that sustain the anti-tumoral response. Therefore, the development and progression of cancer is shaped by the cross-talk between a tumor and the host’s immune system; consequently, a deeper understanding of the interactions between immune cells and the tumor microenvironment is a matter of urgency improve the success of cancer therapy.

In recent years, cancer treatment has undergone a remarkable transformation through the use of new therapeutic modalities alongside traditional treatments, with novel developments including immune checkpoint-targeted antibodies, antibody–drug conjugates, cell-based therapies, small-molecule targeted agents, and gene therapy. These cutting-edge therapeutic modalities allow precise and personalized tumor targeting, with the potential to prevent disease progression and provide patients with increased therapeutic comfort. However, these therapeutic strategies still present untapped potential, and full understanding of the merits and limitations of these treatment modalities will provide new perspectives for clinical practice and oncological research.

Through this Special Issue, we aim to bring together the latest research, clinical studies, and expert opinions on immunotherapy and targeted therapy in solid cancer, and we prospect to provide an up-to-date view on the state-of-the-art in basic and translational cancer immunotherapy research. Areas of interest include, but are not limited to, the following: cell-based immunotherapy; combination therapeutic approaches; tumor progression/metastasis, immune escape, and resistance to targeted immunotherapy; high-throughput approaches to discover novel immunomodulatory drugs; biomarkers for immunotherapy; genetic/epigenetic traits for immunotherapy.

Prof. Dr. Monica Neagu
Guest Editor

Dr. Gheorghita Isvoranu
Guest Editor Assistant

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 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. Medicina is an international peer-reviewed open access monthly 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 2200 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 immunotherapy
  • cancer targeted therapy
  • immune checkpoint targeted therapy
  • cell therapy in cancer
  • signal transduction inhibitors
  • small molecules of cancer drugs
  • tumor microenvironment
  • efficacy biomarkers for cancer therapy
  • mechanisms of resistance

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Published Papers (3 papers)

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Review

23 pages, 958 KB  
Review
Cutaneous Melanoma in the Context of Aging
by Monica Neagu, Carolina Constantin and Sabina Zurac
Medicina 2025, 61(12), 2115; https://doi.org/10.3390/medicina61122115 - 27 Nov 2025
Viewed by 497
Abstract
Ageing is sustained by a complex network of cellular and molecular mechanisms. The main mechanisms are cellular senescence, telomere attrition, gene expression changes, metabolic dysregulations, oxidative stress and epigenetic modifications such as DNA methylation. All these networks can harbor the initiation of age-related [...] Read more.
Ageing is sustained by a complex network of cellular and molecular mechanisms. The main mechanisms are cellular senescence, telomere attrition, gene expression changes, metabolic dysregulations, oxidative stress and epigenetic modifications such as DNA methylation. All these networks can harbor the initiation of age-related diseases, skin cancer included. The studies published in the last years linking ageing and skin cancers focus on basal and squamous carcinomas, melanomas and Merkel cell carcinomas. Our review will focus on skin melanomas as one of the aggressive skin cancers along with Merkel cell carcinomas. Several long-term studies conducted on large populations have shown that in elderly individuals melanoma related to photo-exposure has doubled in the last decade. The clinic-pathological pattern of skin melanomas is different in aged patients and is guided also by immune-related mechanisms. Besides sun exposure, metabolic deregulations and obesity can be risk factors in melanomas. Controversial results were published on obesity risk in melanomas; however, the adipose tissue favors increased cytokines and growth factors production contributing to melanoma aggressiveness. Moreover, immunotherapy that is not offered in geriatric patients as often as in young ones has proven to be as efficient as in younger ones, although the aged-related co-morbidities can impede the immunotherapy choice. Without being exhaustive, our review has synthesized current research and critically assessed the links between aging as a normal physiological process to the initiation and propagation of skin cancers, focusing on cutaneous melanoma. The review highlights the differences at various levels of skin melanoma developed in aged patients compared to younger one and gives the general outlines for diagnosis, prognosis and therapeutical approaches in aged patients. Full article
(This article belongs to the Special Issue Updates on the Changing Landscape of Immunotherapy and Targeted Therapy in Cancer)
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20 pages, 1223 KB  
Review
Mechanistic Insights and Advances of Bispecific T Cell Engaging Antibodies Therapy in Multiple Myeloma
by Ting Fang Tang, Chin Sum Cheong, Chung Yeng Looi, Won Fen Wong and Gin Gin Gan
Medicina 2025, 61(12), 2113; https://doi.org/10.3390/medicina61122113 - 27 Nov 2025
Viewed by 718
Abstract
Multiple myeloma (MM) is a clonal malignancy of terminally differentiated plasma cells characterized by bone marrow infiltration and excessive production of monoclonal immunoglobulins, leading to end-organ damage such as osteolytic bone lesions. Despite substantial therapeutic progress achieved with proteasome inhibitors, immunomodulatory drugs, and [...] Read more.
Multiple myeloma (MM) is a clonal malignancy of terminally differentiated plasma cells characterized by bone marrow infiltration and excessive production of monoclonal immunoglobulins, leading to end-organ damage such as osteolytic bone lesions. Despite substantial therapeutic progress achieved with proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, multiple myeloma remains incurable, and outcomes for triple-class-refractory patients remain dismal, with median survival below one year. Bispecific T cell engaging antibodies (TCEs) have recently emerged as a promising immunotherapeutic approach capable of redirecting cytotoxic T cells to eliminate malignant plasma cells. These engineered antibodies simultaneously engage CD3 on T cells and a tumor-associated antigen such as B cell maturation antigen (BCMA), G protein-coupled receptor family C group 5 member D (GPRC5D), or Fc receptor homolog 5 (FcRH5), thereby forming an immune synapse that triggers T cell activation, cytokine secretion, and perforin–granzyme-mediated apoptosis of the targeted B cell. This review summarizes the molecular design, mechanism of action, and clinical development of TCEs in MM, encompassing early bi-specific T cell engagers (BiTE) constructs such as AMG 420 and next-generation IgG-like molecules including teclistamab. Pivotal clinical trials have demonstrated overall response rates between 43% and 73%, accompanied by durable remissions and manageable safety profiles. Future directions include earlier-line integration, synergistic combinations with immunomodulatory or costimulatory agents, and the development of trispecific formats to overcome antigen escape and T cell exhaustion. Collectively, TCEs represent a paradigm shift toward durable, immune-mediated disease control in multiple myeloma. Full article
(This article belongs to the Special Issue Updates on the Changing Landscape of Immunotherapy and Targeted Therapy in Cancer)
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18 pages, 741 KB  
Review
Immunopathogenesis and Therapeutic Implications in Basal Cell Carcinoma: Current Concepts and Future Directions
by Helen C. Steel, Theresa M. Rossouw, Ronald Anderson, Lindsay Anderson, Daniel van Tonder, Teresa Smit and Bernardo Leon Rapoport
Medicina 2025, 61(11), 1914; https://doi.org/10.3390/medicina61111914 - 25 Oct 2025
Viewed by 600
Abstract
This review is focused on understanding the reasons why basal cell carcinoma (BCC), the most common, increasingly prevalent cancer, is classified as an “immune excluded” malignancy. It is, despite manifesting one of the highest tumor mutational burdens of any solid human malignancy, considered [...] Read more.
This review is focused on understanding the reasons why basal cell carcinoma (BCC), the most common, increasingly prevalent cancer, is classified as an “immune excluded” malignancy. It is, despite manifesting one of the highest tumor mutational burdens of any solid human malignancy, considered to be a biomarker of enhanced tumor immunogenicity and efficacy of tumor-targeted immunotherapy. Following a brief clinical overview, the balance of the review addresses important translational issues based on recent insights into the mechanisms underpinning immune exclusion/evasion in BCC. These include, firstly, the role of infectious agents and non-infectious potential causes of predisposition for and/or exacerbation of disease development and progression. Secondly, an overview of existing and emerging novel therapeutic strategies to ameliorate immune exclusion in BCC based on targeting several key immunosuppressive mechanisms. These are (i) inappropriate activation of the hedgehog signaling pathway (HHSP) due to formation of key driver mutations; (ii) interference with the presentation of tumor-specific antigens/neoantigens to cytotoxic T-cells; (iii) attenuation of the influx of anti-tumor natural killer cells; (iv) the recruitment and activation of immune suppressive regulatory T-cells; and (v) localized and systemic immune dysfunction achieved via elevated levels of soluble co-inhibitory immune checkpoint proteins (ICPs). The final section is focused on current and emerging pharmacologic and immune-based therapies. Full article
(This article belongs to the Special Issue Updates on the Changing Landscape of Immunotherapy and Targeted Therapy in Cancer)
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