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Molecular-Targeted Cancer Therapy
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Molecular-Targeted Cancer Therapy

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 19869

Special Issue Editors

Prof. Dr. Yongzhong Du

E-Mail Website
Guest Editor
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310030, China
Interests: biomaterials; targeted drug delivery systems; interventional therapy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jiansong Ji

E-Mail Website
Guest Editor
Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, the Fifth Affiliated Hospital of Wenzhou Medical University, #289 Kuocang road, Liandu district, Lishui, China
Interests: interventional comprehensive treatment of tumor; tumor targeted imaging; tumor targeted therapy; tumor immunotherapy

Special Issue Information

Dear Colleagues,

Cancers have become important diseases threatening human life and health, and their morbidity and mortality are still increasing with every passing year. The development of drugs for cancer diagnosis and treatment has also become a hot research field, with the continuous advancement of the concept of precision medicine. Targeted cancer therapy has become an important clinical strategy, and new molecular-targeted drugs are constantly being discovered and used in the treatment of different tumors, such as sorafenib and gefitinib. Numerous well-established synthetic methods and biological screening assays are paving the way to the discovery and development of new cancer-targeted agents. Additionally, the rapid development of targeted drug-delivery systems is providing new strategies for targeted therapies. Thus, we continue to be devoted to all aspects of recent exploitation for new cancer-targeted agents and biomaterials for targeted delivery as well as controlled release. Both original research and review articles, 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 for publication in this Special Issue.

Prof. Dr. Yongzhong Du
Prof. Dr. Jiansong Ji
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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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-targeted therapy
  • cancer-targeted drug delivery system
  • molecule inhibitor
  • molecular-targeted drugs
  • pharmacological activity of targeted drugs
  • mechanism of cancer-targeted therapy
  • molecular therapeutic targets

Published Papers (6 papers)

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Research

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15 pages, 2827 KiB  
Article
HMGCS2 Mediation of Ketone Levels Affects Sorafenib Treatment Efficacy in Liver Cancer Cells
by Fat-Moon Suk, Chien-Ying Wu, Wan-Chun Chiu, Chia-Ying Chien, Tzu-Lang Chen and Yi-Jen Liao
Molecules 2022, 27(22), 8015; https://doi.org/10.3390/molecules27228015 - 18 Nov 2022
Cited by 4 | Viewed by 2592
Abstract
Primary liver cancer is the fifth leading death of cancers in men, and hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancer cases. Sorafenib is a first-line drug for advanced-stage HCC patients. Sorafenib is a multi-target kinase inhibitor that blocks [...] Read more.
Primary liver cancer is the fifth leading death of cancers in men, and hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancer cases. Sorafenib is a first-line drug for advanced-stage HCC patients. Sorafenib is a multi-target kinase inhibitor that blocks tumor cell proliferation and angiogenesis. Despite sorafenib treatment extending survival, some patients experience side effects, and sorafenib resistance does occur. 3-Hydroxymethyl glutaryl-CoA synthase 2 (HMGCS2) is the rate-limiting enzyme for ketogenesis, which synthesizes the ketone bodies, β-hydroxybutyrate (β-HB) and acetoacetate (AcAc). β-HB is the most abundant ketone body which is present in a 4:1 ratio compared to AcAc. Recently, ketone body treatment was found to have therapeutic effects against many cancers by causing metabolic alternations and cancer cell apoptosis. Our previous publication showed that HMGCS2 downregulation-mediated ketone body reduction promoted HCC clinicopathological progression through regulating c-Myc/cyclin D1 and caspase-dependent signaling. However, whether HMGCS2-regulated ketone body production alters the sensitivity of human HCC to sorafenib treatment remains unclear. In this study, we showed that HMGCS2 downregulation enhanced the proliferative ability and attenuated the cytotoxic effects of sorafenib by activating expressions of phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-P38, and p-AKT. In contrast, HMGCS2 overexpression decreased cell proliferation and enhanced the cytotoxic effects of sorafenib in HCC cells by inhibiting ERK activation. Furthermore, we showed that knockdown HMGCS2 exhibited the potential migratory ability, as well as decreasing zonula occludens protein (ZO)-1 and increasing c-Myc expression in both sorafenib-treated Huh7 and HepG2 cells. Although HMGCS2 overexpression did not alter the migratory effect, expressions of ZO-1, c-Myc, and N-cadherin decreased in sorafenib-treated HMGCS2-overexpressing HCC cells. Finally, we investigated whether ketone treatment influences sorafenib sensitivity. We showed that β-HB pretreatment decreased cell proliferation and enhanced antiproliferative effect of sorafenib in both Huh7 and HepG2 cells. In conclusion, this study defined the impacts of HMGCS2 expression and ketone body treatment on influencing the sorafenib sensitivity of liver cancer cells. Full article
(This article belongs to the Special Issue Molecular-Targeted Cancer Therapy)
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16 pages, 3938 KiB  
Article
Tumor Tropic Delivery of Hyaluronic Acid-Poly (D,L-lactide-co-glycolide) Polymeric Micelles Using Mesenchymal Stem Cells for Glioma Therapy
by Xiao-Ling Wang, Wen-Zheng Zhao, Jia-Ze Fan, Le-Chen Jia, Ya-Nan Lu, Ling-Hui Zeng, Yuan-Yuan Lv and Xiao-Yi Sun
Molecules 2022, 27(8), 2419; https://doi.org/10.3390/molecules27082419 - 08 Apr 2022
Cited by 3 | Viewed by 1991
Abstract
Tumor penetration and the accumulation of nanomedicines are crucial challenges in solid tumor therapy. By taking advantage of the MSC tumor-tropic property, we developed a mesenchymal stem cell (MSC)-based drug delivery system in which paclitaxel (PTX)-encapsulating hyaluronic acid-poly (D,L-lactide-co-glycolide) polymeric micelles (PTX/HA-PLGA micelles) [...] Read more.
Tumor penetration and the accumulation of nanomedicines are crucial challenges in solid tumor therapy. By taking advantage of the MSC tumor-tropic property, we developed a mesenchymal stem cell (MSC)-based drug delivery system in which paclitaxel (PTX)-encapsulating hyaluronic acid-poly (D,L-lactide-co-glycolide) polymeric micelles (PTX/HA-PLGA micelles) were loaded for glioma therapy. The results indicated that CD44 overexpressed on the surface of both MSCs and tumor cells not only improved PTX/HA-PLGA micelle loading in MSCs, but also promoted the drug transfer between MSCs and adjacent cancer cells. It was hypothesized that CD44-mediated transcytosis played a crucial role and allowed deep glioma penetration depending on sequential intra–intercellular delivery via endocytosis–exocytosis. MSC-micelles were able to infiltrate from normal brain parenchyma towards contralateral tumors and led to the eradication of glioma. The survival of orthotopic glioma-bearing rats was significantly extended. In conclusion, the MSC-based delivery of HA-PLGA micelles is a potential strategy for tumor-targeting drug delivery. Full article
(This article belongs to the Special Issue Molecular-Targeted Cancer Therapy)
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Review

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20 pages, 1386 KiB  
Review
Molecular-Targeted Therapy of Pediatric Acute Myeloid Leukemia
by Piotr Obszański, Anna Kozłowska, Jakub Wańcowiat, Julia Twardowska, Monika Lejman and Joanna Zawitkowska
Molecules 2022, 27(12), 3911; https://doi.org/10.3390/molecules27123911 - 18 Jun 2022
Cited by 7 | Viewed by 2637
Abstract
Acute myeloid leukemia (AML) accounts for approximately 15–20% of all childhood leukemia cases. The overall survival of children with acute myeloid leukemia does not exceed 82%, and the 5-year event-free survival rates range from 46% to 69%. Such suboptimal outcomes are the result [...] Read more.
Acute myeloid leukemia (AML) accounts for approximately 15–20% of all childhood leukemia cases. The overall survival of children with acute myeloid leukemia does not exceed 82%, and the 5-year event-free survival rates range from 46% to 69%. Such suboptimal outcomes are the result of numerous mutations and epigenetic changes occurring in this disease that adversely affect the susceptibility to treatment and relapse rate. We describe various molecular-targeted therapies that have been developed in recent years to meet these challenges and were or are currently being studied in clinical trials. First introduced in adult AML, novel forms of treatment are slowly beginning to change the therapeutic approach to pediatric AML. Despite promising results of clinical trials investigating new drugs, further clinical studies involving greater numbers of pediatric patients are still needed to improve the outcomes in childhood AML. Full article
(This article belongs to the Special Issue Molecular-Targeted Cancer Therapy)
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15 pages, 1213 KiB  
Review
Potential of Ferritin-Based Platforms for Tumor Immunotherapy
by Xiaoling Xu, Kewei Tian, Xuefang Lou and Yongzhong Du
Molecules 2022, 27(9), 2716; https://doi.org/10.3390/molecules27092716 - 22 Apr 2022
Cited by 12 | Viewed by 2798
Abstract
Ferritin is an iron storage protein that plays a key role in iron homeostasis and cellular antioxidant activity. Ferritin has many advantages as a tumor immunotherapy platform, including a small particle size that allows for penetration into tumor-draining lymph nodes or tumor tissue, [...] Read more.
Ferritin is an iron storage protein that plays a key role in iron homeostasis and cellular antioxidant activity. Ferritin has many advantages as a tumor immunotherapy platform, including a small particle size that allows for penetration into tumor-draining lymph nodes or tumor tissue, a unique structure consisting of 24 self-assembled subunits, cavities that can encapsulate drugs, natural targeting functions, and a modifiable outer surface. In this review, we summarize related research applying ferritin as a tumor immune vaccine or a nanocarrier for immunomodulator drugs based on different targeting mechanisms (including dendritic cells, tumor-associated macrophages, tumor-associated fibroblasts, and tumor cells). In addition, a ferritin-based tumor vaccine expected to protect against a wide range of coronaviruses by targeting multiple variants of SARS-CoV-2 has entered phase I clinical trials, and its efficacy is described in this review. Although ferritin is already on the road to transformation, there are still many difficulties to overcome. Therefore, three barriers (drug loading, modification sites, and animal models) are also discussed in this paper. Notwithstanding, the ferritin-based nanoplatform has great potential for tumor immunotherapy, with greater possibility of clinical transformation. Full article
(This article belongs to the Special Issue Molecular-Targeted Cancer Therapy)
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23 pages, 1648 KiB  
Review
Ferroptosis: A New Road towards Cancer Management
by Iqra Bano, Pavel Horky, Syed Qamar Abbas, Muhammad Majid, Akram Hafiz Muhammad Bilal, Fawad Ali, Tapan Behl, Syed Shams ul Hassan and Simona Bungau
Molecules 2022, 27(7), 2129; https://doi.org/10.3390/molecules27072129 - 25 Mar 2022
Cited by 31 | Viewed by 4284
Abstract
Ferroptosis is a recently described programmed cell death mechanism that is characterized by the buildup of iron (Fe)-dependent lipid peroxides in cells and is morphologically, biochemically, and genetically distinct from other forms of cell death, having emerged to play an important role in [...] Read more.
Ferroptosis is a recently described programmed cell death mechanism that is characterized by the buildup of iron (Fe)-dependent lipid peroxides in cells and is morphologically, biochemically, and genetically distinct from other forms of cell death, having emerged to play an important role in cancer biology. Ferroptosis has significant importance during cancer treatment because of the combination of factors, including suppression of the glutathione peroxidase 4 (Gpx4), cysteine deficiency, and arachidonoyl (AA) peroxidation, which cause cells to undergo ferroptosis. However, the physiological significance of ferroptosis throughout development is still not fully understood. This current review is focused on the factors and molecular mechanisms with the diagrammatic illustrations of ferroptosis that have a role in the initiation and sensitivity of ferroptosis in various malignancies. This knowledge will open a new road for research in oncology and cancer management. Full article
(This article belongs to the Special Issue Molecular-Targeted Cancer Therapy)
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15 pages, 826 KiB  
Review
SOD2, a Potential Transcriptional Target Underpinning CD44-Promoted Breast Cancer Progression
by Nouralhuda Alateyah, Ishita Gupta, Radoslaw Stefan Rusyniak and Allal Ouhtit
Molecules 2022, 27(3), 811; https://doi.org/10.3390/molecules27030811 - 26 Jan 2022
Cited by 12 | Viewed by 4739
Abstract
CD44, a cell-adhesion molecule has a dual role in tumor growth and progression; it acts as a tumor suppressor as well as a tumor promoter. In our previous work, we developed a tetracycline-off regulated expression of CD44’s gene in the breast cancer (BC) [...] Read more.
CD44, a cell-adhesion molecule has a dual role in tumor growth and progression; it acts as a tumor suppressor as well as a tumor promoter. In our previous work, we developed a tetracycline-off regulated expression of CD44’s gene in the breast cancer (BC) cell line MCF-7 (B5 clone). Using cDNA oligo gene expression microarray, we identified SOD2 (superoxide dismutase 2) as a potential CD44-downstream transcriptional target involved in BC metastasis. SOD2 gene belongs to the family of iron/manganese superoxide dismutase family and encodes a mitochondrial protein. SOD2 plays a role in cell proliferation and cell invasion via activation of different signaling pathways regulating angiogenic abilities of breast tumor cells. This review will focus on the findings supporting the underlying mechanisms associated with the oncogenic potential of SOD2 in the onset and progression of cancer, especially in BC and the potential clinical relevance of its various inhibitors. Full article
(This article belongs to the Special Issue Molecular-Targeted Cancer Therapy)
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