Novel Therapeutic Targets in Cancer 2023

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 6987

Special Issue Editor


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Guest Editor
Anschutz Medical Campus, University of Colorado Denver, Denver, CO, USA
Interests: kinase; cytotoxicity; therapy resistance; small molecule; drug delivery; cytokines; chemokine; metastasis and mitochondria
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Special Issue Information

Dear Colleagues,

I am pleased to announce the Special Issue “Novel Therapeutic Targets in Cancer” in Pharmaceuticals is now accepting manuscripts for publication. In recent years, significant advances have been made in the management of cancer with the introduction of targeted therapies and immunotherapy. However, there continues to be an unmet clinical need for patients progressing on novel therapies. Thus, the identification of undiscovered mechanisms involved in tumor progression is critical to improve survival in this population. This Special Issue aims to publish translational articles investigating potential new strategies in cancer treatment. Subjects of interest include novel molecular targets, intrinsic pathways involved in tumor immune escape mechanisms, drug development, physiological and pharmacological bases of drug action, and metabolism. Original articles, reviews, short communications, and editorials are all welcome.

Dr. Carlo Marchetti
Guest Editor

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Keywords

  • kinase
  • cytotoxicity
  • therapy resistance
  • small molecule
  • drug delivery
  • cytokines
  • chemokine
  • metastasis and mitochondria

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Published Papers (3 papers)

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Research

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13 pages, 1413 KiB  
Article
The Correlations between the Intensity of Histopathological Ubiquitin-Specific Protease 11 Staining and Progression of Prostate Cancer
by Jae Heon Kim, Hee Jo Yang, Kwang Woo Lee, Jae Joon Park, Chang-Ho Lee, Youn Soo Jeon, Jae Ho Kim, Suyeon Park, Su Jung Song, Ji-Hye Lee, Ahrim Moon, Yon Hee Kim and Yun Seob Song
Pharmaceuticals 2023, 16(12), 1703; https://doi.org/10.3390/ph16121703 - 8 Dec 2023
Cited by 1 | Viewed by 1221
Abstract
Background: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 [...] Read more.
Background: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. Methods: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient’s age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. Results: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. Conclusions: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets in Cancer 2023)
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Review

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17 pages, 869 KiB  
Review
Reviving a Classic Antigen with a Cutting-Edge Approach: Nanobodies for HER2+ Breast Cancer
by Chiara Castrignano, Federica Di Scipio, Francesco Franco, Barbara Mognetti and Giovanni Nicolao Berta
Pharmaceuticals 2023, 16(6), 794; https://doi.org/10.3390/ph16060794 - 26 May 2023
Cited by 2 | Viewed by 2414
Abstract
The serendipitous discovery of nanobodies (NBs) around two decades ago opened the door to new possibilities for innovative strategies, particularly in cancer treatment. These antigen-binding fragments are derived from heavy-chain-only antibodies naturally found in the serum of camelids and sharks. NBs are an [...] Read more.
The serendipitous discovery of nanobodies (NBs) around two decades ago opened the door to new possibilities for innovative strategies, particularly in cancer treatment. These antigen-binding fragments are derived from heavy-chain-only antibodies naturally found in the serum of camelids and sharks. NBs are an appealing agent for the progress of innovative therapeutic strategies because they combine the advantageous assets of smaller molecules and conventional monoclonal antibodies (mAbs). Moreover, the possibility to produce NBs using bacterial systems reduces manufacturing expenses and speeds up the production process, making them a feasible option for the development of new bio-drugs. Several NBs have been developed over the past 10 years and are currently being tested in clinical trials for various human targets. Here, we provide an overview of the notable structural and biochemical characteristics of NBs, particularly in their application against HER2, an extracellular receptor that often gets aberrantly activated during breast cancer tumorigenesis. The focus is on the recent advancements in diagnostic and therapeutic research up to the present date. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets in Cancer 2023)
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26 pages, 8071 KiB  
Review
Structural Complementarity of Bruton’s Tyrosine Kinase and Its Inhibitors for Implication in B-Cell Malignancies and Autoimmune Diseases
by Asim Najmi, Neelaveni Thangavel, Anugeetha Thacheril Mohanan, Marwa Qadri, Mohammed Albratty, Safeena Eranhiyil Ashraf, Safaa Fathy Saleh, Maryam Nayeem and Syam Mohan
Pharmaceuticals 2023, 16(3), 400; https://doi.org/10.3390/ph16030400 - 7 Mar 2023
Cited by 1 | Viewed by 2668
Abstract
Bruton’s tyrosine kinase (BTK) is a critical component in B-cell receptor (BCR) signaling and is also expressed in haematogenic and innate immune cells. Inhibition of BTK hyperactivity is implicated in B-cell malignancies and autoimmune diseases. This review derives the structural complementarity of the [...] Read more.
Bruton’s tyrosine kinase (BTK) is a critical component in B-cell receptor (BCR) signaling and is also expressed in haematogenic and innate immune cells. Inhibition of BTK hyperactivity is implicated in B-cell malignancies and autoimmune diseases. This review derives the structural complementarity of the BTK-kinase domain and its inhibitors from recent three-dimensional structures of inhibitor-bound BTK in the protein data bank (PDB). Additionally, this review analyzes BTK-mediated effector responses of B-cell development and antibody production. Covalent inhibitors contain an α, β-unsaturated carbonyl moiety that forms a covalent bond with Cys481, stabilizing αC-helix in inactive-out conformation which inhibits Tyr551 autophosphorylation. Asn484, located two carbons far from Cys481, influences the stability of the BTK-transition complex. Non-covalent inhibitors engage the BTK-kinase domain through an induced-fit mechanism independent of Cys481 interaction and bind to Tyr551 in the activation kink resulting in H3 cleft, determining BTK selectivity. Covalent and non-covalent binding to the kinase domain of BTK shall induce conformational changes in other domains; therefore, investigating the whole-length BTK conformation is necessary to comprehend BTK’s autophosphorylation inhibition. Knowledge about the structural complementarity of BTK and its inhibitors supports the optimization of existing drugs and the discovery of drugs for implication in B-cell malignancies and autoimmune diseases. Full article
(This article belongs to the Special Issue Novel Therapeutic Targets in Cancer 2023)
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