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Targeted Therapy of Cancer: Innovative Drugs and Molecular Tools
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Targeted Therapy of Cancer: Innovative Drugs and Molecular Tools

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: closed (30 April 2025) | Viewed by 3302

Special Issue Editors

Prof. Dr. Rodolfo Ippoliti

E-Mail Website
Guest Editor
Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Interests: drug delivery; toxins; immune conjugates; cancer therapy; protein structure; protein toxins; immunotoxins; endocytosis
Special Issues, Collections and Topics in MDPI journals
Dr. Francesco Giansanti

E-Mail Website
Guest Editor
1. Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 Coppito, AQ, Italy
2. Interuniversity Consortium Biostructures and Biosystems National Institute (INBB), 00136 Rome, Italy
Interests: transferrins; lactoferrin; ovotransferrin; saporin; ADCs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Modern medicine has focused its attention on the possibility of delivering drugs in a controlled manner, particularly as soon as more attractive targets have emerged, and new molecular tools have become available. Targeted cancer therapy has become an innovative strategy, with new drugs being constantly discovered and applied in the treatment of various types of tumors, enabling precision and personalized medicine. A major challenge concerns the safe delivery of drugs (minimizing side-effects) and the potential exploitation of novel molecular tools, such as miRNA, CRISPR-Cas9, aptamers, and EVs. These approaches complement the use of more classical methods, such as antibody-based therapies, which still require innovation to become more effective.

This Special Issue of the International Journal of Molecular Sciences aims to focus on the use of innovative drugs and molecular tools to target cancer cells in vivo, with particular attention to the mechanisms of action and the structural characteristics of novel therapeutic agents. We look forward to exploring all aspects of recent applications of cancer-targeted agents and biomaterials for controlled drug release. Contributions in the form of original research articles and reviews, focusing on the rational design, synthesis, and/or biological evaluation of various agents (including small molecules, nano-drugs, natural products, endogenous molecules, antibodies, vaccines, etc.) as potential cancer therapeutics, are welcome for submission to this Special Issue.

Prof. Dr. Rodolfo Ippoliti
Dr. Francesco Giansanti
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 short 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • drug delivery
  • targeted therapies
  • cancer therapy
  • molecular targets
  • precision medicine
  • molecular therapeutic targets

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Published Papers (4 papers)

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Research

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17 pages, 3028 KiB  
Article
Enhancing the Efficacy of CAR-T Cell Production Using BX795 and Rosuvastatin in a Serum-Free Medium
by Abed Al-Kader Yassin, Rajashri Banerji, Baisali Bhattacharya, Olga Radinsky, Uzi Hadad, Bar Kaufman and Angel Porgador
Int. J. Mol. Sci. 2025, 26(7), 2988; https://doi.org/10.3390/ijms26072988 - 25 Mar 2025
Viewed by 699
Abstract
Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a transformative approach for cancer treatment, demonstrating remarkable success in patients with relapsed and refractory hematological malignancies. However, challenges persist in optimizing CAR-T cell production and improving therapeutic outcomes. One of the major hurdles [...] Read more.
Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a transformative approach for cancer treatment, demonstrating remarkable success in patients with relapsed and refractory hematological malignancies. However, challenges persist in optimizing CAR-T cell production and improving therapeutic outcomes. One of the major hurdles is the efficiency of retroviral or lentiviral transduction during CAR-T cell manufacturing. Additionally, the heterogeneity of T-cell populations isolated from patients can impact CAR-T cell effectiveness and persistence in vivo. This article explores a novel strategy to address these challenges by focusing on serum-free medium and additive optimization. We propose a unique approach that incorporates the culturing of T cells in Nutri-T medium, along with 24 h of exposure to combined low concentrations of BX795 and rosuvastatin, to enhance the transduction efficacy and functionality of CAR-T cells. The results presented here provide promising insights into the potential of this strategy to produce more effective CAR-T cells for immunotherapy, ultimately advancing the field and benefiting cancer patients worldwide. Full article
(This article belongs to the Special Issue Targeted Therapy of Cancer: Innovative Drugs and Molecular Tools)
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Review

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22 pages, 2075 KiB  
Review
CD320 Receptor and Vitamin B12 as Potential Targets for Anti-Cancer Therapy
by Ainur Tolymbekova and Larissa Lezina
Int. J. Mol. Sci. 2025, 26(12), 5652; https://doi.org/10.3390/ijms26125652 - 12 Jun 2025
Viewed by 923
Abstract
Despite the development of a wide plethora of different anticancer agents, most of them are not used for patient treatment due to adverse effects caused by untargeted cytotoxicity. To prevent this unwanted toxicity, it is necessary to develop therapies discriminating between healthy and [...] Read more.
Despite the development of a wide plethora of different anticancer agents, most of them are not used for patient treatment due to adverse effects caused by untargeted cytotoxicity. To prevent this unwanted toxicity, it is necessary to develop therapies discriminating between healthy and cancerous cells. One possible method is to target proteins overexpressed in cancer but not in normal cells. CD320 is a receptor responsible for the uptake of the transcobalamin-bound fraction of vitamin B12 (cobalamin), which is necessary for DNA synthesis, and thus, cell proliferation. CD320 was shown to be overexpressed in many cancers and its potential role as an early cancer biomarker was confirmed in several studies. Consequently, CD320 may represent a promising anti-cancer therapy target. This review summarizes the current advances and perspectives of anti-cancer CD320 targeting therapy, including therapeutic conjugates of vitamin B12, CD320-specific antibodies and nanobodies, nanoparticles loaded with cytotoxic drugs, porphyrin, and the potential of targeted CD320 therapy in attenuation of tumor tissues. Given the growing interest in CD320 as a novel target for anti-cancer therapy, further in vivo studies are required for the investigation of CD320 targeting effects on systemic cytotoxicity. Full article
(This article belongs to the Special Issue Targeted Therapy of Cancer: Innovative Drugs and Molecular Tools)
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15 pages, 500 KiB  
Review
Multifaceted Roles of Guanylate-Binding Proteins in Cancer
by Derin Ahmetoglu, Haoyi Zheng, Aaron Swart, Hua Zhu and Ming Li
Int. J. Mol. Sci. 2025, 26(12), 5477; https://doi.org/10.3390/ijms26125477 - 7 Jun 2025
Viewed by 450
Abstract
Guanylate-binding proteins (GBPs), encompassing GBP1 through GBP7 in humans, are interferon-inducible large GTPases of the dynamin superfamily, renowned for their pivotal roles in cell-autonomous immunity against intracellular pathogens such as viruses, bacteria, and protozoa. By recognizing pathogen-associated molecular patterns (PAMPs) and danger-associated molecular [...] Read more.
Guanylate-binding proteins (GBPs), encompassing GBP1 through GBP7 in humans, are interferon-inducible large GTPases of the dynamin superfamily, renowned for their pivotal roles in cell-autonomous immunity against intracellular pathogens such as viruses, bacteria, and protozoa. By recognizing pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), GBPs orchestrate lysosomal targeting, regulate inflammatory cascades, and modulate apoptosis to protect host tissues from immune-mediated damage. Beyond their foundational roles in immunity, GBPs exhibit context-dependent effects in human cancer, promoting malignancy in some tumors through enhanced immune signaling, inhibition of apoptosis, and resistance to therapies, or suppressing tumor growth through immune activation and cell cycle regulation. This comprehensive review explores the structural intricacies, immune functions, and multifaceted contributions of human GBPs to cancer, delving into their molecular mechanisms, prognostic potential, and therapeutic implications. We incorporate the latest insights to highlight how understanding GBP regulation could reshape cancer treatment strategies. Full article
(This article belongs to the Special Issue Targeted Therapy of Cancer: Innovative Drugs and Molecular Tools)
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29 pages, 978 KiB  
Review
The p130Cas-Crk/CrkL Axis: A Therapeutic Target for Invasive Cancers Unveiled by Collaboration Among p130Cas, Crk, and CrkL
by Pegah Farhadi and Taeju Park
Int. J. Mol. Sci. 2025, 26(9), 4017; https://doi.org/10.3390/ijms26094017 - 24 Apr 2025
Viewed by 563
Abstract
Numerous studies have documented the involvement of p130Cas (Crk-associated substrate) in a wide range of cellular processes across different types of cells. These processes encompass cell transformation, the connection between the extracellular matrix and the actin cytoskeleton, cell migration and invasion, and cardiovascular [...] Read more.
Numerous studies have documented the involvement of p130Cas (Crk-associated substrate) in a wide range of cellular processes across different types of cells. These processes encompass cell transformation, the connection between the extracellular matrix and the actin cytoskeleton, cell migration and invasion, and cardiovascular development. Moreover, p130Cas has been associated with the regulation of various physiological processes, including mammary, bone, brain, muscle, and liver homeostasis. The diverse functions of p130Cas can be attributed to its possession of multiple protein–protein interaction domains, which sets it apart as a unique class of adaptor protein. It is well established that p130Cas interacts critically with the CT10 regulator of kinase (Crk) adaptor protein family members, including CrkII, CrkI, and Crk-like (CrkL), which is the basis for the naming of the Cas family. The Crk family proteins play a crucial role in integrating signals from various sources, such as growth factors, extracellular matrix molecules, bacterial pathogens, and apoptotic cells. An increasing body of evidence suggests that the dysregulation of Crk family proteins is linked to various human diseases, including cancer and increased susceptibility to pathogen infections. This review focuses primarily on the structural and functional aspects of the interaction between p130Cas and the Crk family proteins, providing insights into how these proteins regulate specific signaling events. Furthermore, we delve into the functions of p130Cas and the Crk family proteins in both normal and tumor cells to gain a comprehensive understanding of their collaborative roles in cellular physiology and pathology. This review demonstrates that tumor cell migration and invasion are the two cellular functions that have been studied the most for the p130Cas-Crk/CrkL axis. Understanding the tumor cell migration and invasion that require both p130Cas and Crk/CrkL is necessary to further evaluate the role of the p130Cas-Crk/CrkL axis in cancer. Establishing the contribution of the p130Cas-Crk/CrkL axis to cancer will facilitate the development of cancer drugs targeting the axis to inhibit cancer cell dissemination and improve patient outcomes. Full article
(This article belongs to the Special Issue Targeted Therapy of Cancer: Innovative Drugs and Molecular Tools)
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