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New Targeted Therapies in Cancer-2024
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New Targeted Therapies in Cancer-2024

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 9931

Special Issue Editor

Dr. Rosaria Chilà

E-Mail Website
Guest Editor
IFOM ETS - The AIRC Institute of Molecular Oncology, 20139 Milan, Italy
Interests: colorectal cancer; targeted therapy; personalized medicine; preclinical research models

Special Issue Information

Dear Colleagues,

Finding useful therapeutic solutions to fight cancer is a clinical need. The conventional chemotherapeutic approaches are effective in different tumor settings, but often cause important side effects that strongly impair the patients’ quality of life. The idea of targeted therapy—targeting a specific genetic alteration, present in the tumor but not in normal tissues—is strongly improving the standard-of-care of many cancers (e.g., leukemia, colorectal, gastric, mammary): targeted therapies, in fact, specifically block cancer cells proliferation, decreasing the risk of treatment-associated off-target effects.

Different molecular targets have been explored, such as growth factors, cell surface molecules and receptors, but also non-coding RNAs and entire signaling pathways. Molecules targeting BCR-ABL, BRAF, MEK, EGFR, ALK are few examples of targeted therapies that showed important results in cancer patients. However, depending the effectiveness on the presence of the altered target, the number of patients taking advantage from these treatments is limited. In addition, low response and resistance to targeted drugs have been documented, together with unexpected side effects. Just few molecules among hundreds of potential drug candidates reach the market, therefore further investigation is warranted.

Nowadays, the huge progresses of technological tools allow a deep investigation of tumor heterogeneity and clonality, essential in determining the success of targeted therapies. This Special Issue is aimed to highlight recent discoveries in the field of New Targeted Therapies in Cancer, concerning different kind of molecules, alternative therapeutic strategies and novel targets.

Dr. Rosaria Chilà
Guest Editor

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

  • targeted therapy
  • personalized medicine
  • side effects
  • molecular targets
  • cancer treatment
  • mutations

Published Papers (6 papers)

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Research

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10 pages, 3476 KiB  
Article
Investigation of the Nanoparticulation Method and Cell-Killing Effect following the Mitochondrial Delivery of Hydrophobic Porphyrin-Based Photosensitizers
by Rina Naganawa, Hanjun Zhao, Yuta Takano, Masatoshi Maeki, Manabu Tokeshi, Hideyoshi Harashima and Yuma Yamada
Int. J. Mol. Sci. 2024, 25(8), 4294; https://doi.org/10.3390/ijms25084294 - 12 Apr 2024
Viewed by 373
Abstract
Photodynamic therapy is expected to be a less invasive treatment, and strategies for targeting mitochondria, the main sources of singlet oxygen, are attracting attention to increase the efficacy of photodynamic therapy and reduce its side effects. To date, we have succeeded in encapsulating [...] Read more.
Photodynamic therapy is expected to be a less invasive treatment, and strategies for targeting mitochondria, the main sources of singlet oxygen, are attracting attention to increase the efficacy of photodynamic therapy and reduce its side effects. To date, we have succeeded in encapsulating the photosensitizer rTPA into MITO-Porter (MP), a mitochondria-targeted Drug Delivery System (DDS), aimed at mitochondrial delivery of the photosensitizer while maintaining its activity. In this study, we report the results of our studies to alleviate rTPA aggregation in an effort to improve drug efficacy and assess the usefulness of modifying the rTPA side chain to improve the mitochondrial retention of MITO-Porter, which exhibits high therapeutic efficacy. Conventional rTPA with anionic side chains and two rTPA analogs with side chains that were converted to neutral or cationic side chains were encapsulated into MITO-Porter. Low-MP (MITO-Porter with Low Drug/Lipid) exhibited high drug efficacy for all three types of rTPA, and in Low-MP, charged rTPA-encapsulated MP exhibited high drug efficacy. The cellular uptake and mitochondrial translocation capacities were similar for all particles, suggesting that differences in aggregation rates during the incorporation of rTPA into MITO-Porter resulted in differences in drug efficacy. Full article
(This article belongs to the Special Issue New Targeted Therapies in Cancer-2024)
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Review

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16 pages, 617 KiB  
Review
Targeting HER2 in Gastroesophageal Adenocarcinoma: Molecular Features and Updates in Clinical Practice
by Maria Bonomi, Daniele Spada, Gian Luca Baiocchi, Andrea Celotti, Matteo Brighenti and Giulia Grizzi
Int. J. Mol. Sci. 2024, 25(7), 3876; https://doi.org/10.3390/ijms25073876 - 30 Mar 2024
Viewed by 659
Abstract
Gastroesophageal adenocarcinoma (GEA) is one of the principal causes of death related to cancer globally. Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor which is found to be overexpressed or amplified in approximately 20% of GEA cases. In GEA, [...] Read more.
Gastroesophageal adenocarcinoma (GEA) is one of the principal causes of death related to cancer globally. Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor which is found to be overexpressed or amplified in approximately 20% of GEA cases. In GEA, the identification of HER2-positive status is crucial to activate a specific anti-HER2 targeted therapy. The landmark ToGA trial demonstrated the superiority of adding trastuzumab to platinum-based chemotherapy, becoming the first-line standard of treatment. However, unlike breast cancer, the efficacy of other anti-HER2 drugs, such as lapatinib, pertuzumab, and T-DM1, has failed to improve outcomes in advanced and locally advanced resectable GEA. Recently, the combination of trastuzumab with pembrolizumab, along with chemotherapy, and the development of trastuzumab deruxtecan, with its specific bystander activity, demonstrated improved outcomes, renewing attention in the treatment of this disease. This review will summarise historical and emerging therapies for the treatment of HER2-positive GEA, with a section dedicated to the HER2 molecular pathway and the use of novel blood biomarkers, such as circulating tumour DNA and circulating tumour cells, which may be helpful in the future to guide treatment decisions. Full article
(This article belongs to the Special Issue New Targeted Therapies in Cancer-2024)
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28 pages, 2751 KiB  
Review
Targeting Farnesoid X Receptor in Tumor and the Tumor Microenvironment: Implication for Therapy
by Miljana Nenkov, Yihui Shi, Yunxia Ma, Nikolaus Gaßler and Yuan Chen
Int. J. Mol. Sci. 2024, 25(1), 6; https://doi.org/10.3390/ijms25010006 - 19 Dec 2023
Viewed by 1813
Abstract
The farnesoid-X receptor (FXR), a member of the nuclear hormone receptor superfamily, can be activated by bile acids (BAs). BAs binding to FXR activates BA signaling which is important for maintaining BA homeostasis. FXR is differentially expressed in human organs and exists in [...] Read more.
The farnesoid-X receptor (FXR), a member of the nuclear hormone receptor superfamily, can be activated by bile acids (BAs). BAs binding to FXR activates BA signaling which is important for maintaining BA homeostasis. FXR is differentially expressed in human organs and exists in immune cells. The dysregulation of FXR is associated with a wide range of diseases including metabolic disorders, inflammatory diseases, immune disorders, and malignant neoplasm. Recent studies have demonstrated that FXR influences tumor cell progression and development through regulating oncogenic and tumor-suppressive pathways, and, moreover, it affects the tumor microenvironment (TME) by modulating TME components. These characteristics provide a new perspective on the FXR-targeted therapeutic strategy in cancer. In this review, we have summarized the recent research data on the functions of FXR in solid tumors and its influence on the TME, and discussed the mechanisms underlying the distinct function of FXR in various types of tumors. Additionally, the impacts on the TME by other BA receptors such as takeda G protein-coupled receptor 5 (TGR5), sphingosine-1-phosphate receptor 2 (S1PR2), and muscarinic receptors (CHRM2 and CHRM3), have been depicted. Finally, the effects of FXR agonists/antagonists in a combination therapy with PD1/PD-L1 immune checkpoint inhibitors and other anti-cancer drugs have been addressed. Full article
(This article belongs to the Special Issue New Targeted Therapies in Cancer-2024)
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14 pages, 2242 KiB  
Review
Mesenchymal–Epithelial Transition Kinase Inhibitor Therapy in Patients with Advanced Papillary Renal-Cell Carcinoma: A Systematic Review and Meta-Analysis
by Francisco Cezar Aquino de Moraes, Maysa Vilbert, Vinícius Freire Costa Alves, Gustavo de Oliveira Almeida, Jonathan N. Priantti, Thiago Madeira, Carlos Stecca, Marianne Rodrigues Fernandes and Ney Pereira Carneiro dos Santos
Int. J. Mol. Sci. 2023, 24(24), 17582; https://doi.org/10.3390/ijms242417582 - 18 Dec 2023
Viewed by 1163
Abstract
Papillary subtypes of renal-cell carcinoma (pRCC) represent 10–15% of the cases and commonly have MET alterations. This systematic review and single-arm meta-analysis evaluated MET inhibitor therapy (METi) efficacy and safety in adults with confirmed advanced pRCC. The search strategy included PubMed, Web-of-science, Cochrane, [...] Read more.
Papillary subtypes of renal-cell carcinoma (pRCC) represent 10–15% of the cases and commonly have MET alterations. This systematic review and single-arm meta-analysis evaluated MET inhibitor therapy (METi) efficacy and safety in adults with confirmed advanced pRCC. The search strategy included PubMed, Web-of-science, Cochrane, and Scopus. We used the DerSimonian/Laird random effect model for all analyses; p-value < 5% was considered significant, and heterogeneity was assessed with I2. Three clinical trials and six cohort studies were included with 504 patients; 31% were MET-driven. Our pooled analysis demonstrated an objective response rate (ORR) in MET-driven, MET-independent, and overall patients of: 36% (95%CI: 10–62), 0% (95%CI: 0–3), and 21% (95%CI: 1–41), respectively. One-year disease control and progression-free survival rates were, respectively, 70% (95%CI: 52–88) and 15% (95%CI: 10–20). Twelve- and twenty-four-month survival rates were, respectively, 43% (95%CI: 23–64) and 10% (95%CI: 0–30). The prevalence of adverse events of any grade and grades 3–5 were 96% (95%CI: 91–100) and 44% (95%CI: 37–50), respectively. We suggest METi has anti-tumor activity and is tolerable in patients with advanced pRCC. Full article
(This article belongs to the Special Issue New Targeted Therapies in Cancer-2024)
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17 pages, 3191 KiB  
Review
RUNX2 and Cancer
by Tsung-Chieh Lin
Int. J. Mol. Sci. 2023, 24(8), 7001; https://doi.org/10.3390/ijms24087001 - 10 Apr 2023
Cited by 8 | Viewed by 2322
Abstract
Runt-related transcription factor 2 (RUNX2) is critical for the modulation of chondrocyte osteoblast differentiation and hypertrophy. Recently discovered RUNX2 somatic mutations, expressional signatures of RUNX2 in normal tissues and tumors, and the prognostic and clinical significance of RUNX2 in many types of cancer [...] Read more.
Runt-related transcription factor 2 (RUNX2) is critical for the modulation of chondrocyte osteoblast differentiation and hypertrophy. Recently discovered RUNX2 somatic mutations, expressional signatures of RUNX2 in normal tissues and tumors, and the prognostic and clinical significance of RUNX2 in many types of cancer have attracted attention and led RUNX2 to be considered a biomarker for cancer. Many discoveries have illustrated the indirect and direct biological functions of RUNX2 in orchestrating cancer stemness, cancer metastasis, angiogenesis, proliferation, and chemoresistance to anticancer compounds, warranting further exploration of the associated mechanisms to support the development of a novel therapeutic strategy. In this review, we focus mainly on critical and recent research developments, including RUNX2’s oncogenic activities, by summarizing and integrating the findings on somatic mutations of RUNX2, transcriptomic studies, clinical information, and discoveries about how the RUNX2-induced signaling pathway modulates malignant progression in cancer. We also comprehensively discuss RUNX2 RNA expression in a pancancer panel and in specific normal cell types at the single-cell level to indicate the potential cell types and sites for tumorigenesis. We expect this review to shed light on the recent mechanistical findings and modulatory role of RUNX2 in cancer progression and provide biological information that can guide new research in this field. Full article
(This article belongs to the Special Issue New Targeted Therapies in Cancer-2024)
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19 pages, 1452 KiB  
Review
Polydopamine-Based Material and Their Potential in Head and Neck Cancer Therapy—Current State of Knowledge
by Marta Witkowska, Ewelina Golusińska-Kardach, Wojciech Golusiński and Ewa Florek
Int. J. Mol. Sci. 2023, 24(5), 4890; https://doi.org/10.3390/ijms24054890 - 03 Mar 2023
Cited by 1 | Viewed by 2038
Abstract
Head and neck cancers (HNC) are among the most common cancers in the world. In terms of frequency of occurrence in the world, HNC ranks sixth. However, the problem of modern oncology is the low specificity of the therapies used, which is why [...] Read more.
Head and neck cancers (HNC) are among the most common cancers in the world. In terms of frequency of occurrence in the world, HNC ranks sixth. However, the problem of modern oncology is the low specificity of the therapies used, which is why most of the currently used chemotherapeutic agents have a systemic effect. The use of nanomaterials could overcome the limitations of traditional therapies. Researchers are increasingly using polydopamine (PDA) in nanotherapeutic systems for HNC due to its unique properties. PDA has found applications in chemotherapy, photothermal therapy, targeted therapy, and combination therapies that facilitate better carrier control for the effective reduction of cancer cells than individual therapies. The purpose of this review was to present the current knowledge on the potential use of polydopamine in head and neck cancer research. Full article
(This article belongs to the Special Issue New Targeted Therapies in Cancer-2024)
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