Emerging Anti-cancer and Cellular Targets and Their Mechanism(s) of Action as New Tools for Therapeutics Approaches

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (10 January 2024) | Viewed by 5499

Special Issue Editors


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Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
Interests: neuroinflammation; central nervous system; degeneration; molecular pathways; protein trafficking
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Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D׳Alcontres, 31-98166 Messina, Italy
Interests: molecular biology; biotechnology; neuroinflammation; central nervous system; molecular pathways

Special Issue Information

Dear Colleagues,

Cancer cells at the center of tumors respond to varied local hypoxic conditions, activating signaling pathways and promoting synthesis and release of chemokines and growth factors (GFs) that transform the local environment. Immune, endothelial, and neuronal, among other cell types, express receptors that respond to these oncogenic signals. In this process, cancer cells with invasive and anchorage-free survival properties could disseminate and establish metastatic tumors. Thus, targeting and understanding the communication between tumor cells and the adjacent vasculature is the basis of novel anti-tumor therapies. More recent studies have identified abrupt cellular signaling pathways as underlying mechanisms for the development of cancer drug resistance. Some key processes involved in drug resistance include tumor heterogeneity, reactivation of drug targets, hyperactivation of alternative pathways, cross-talk with the microenvironment, altered DNA response and its repair, modification in epigenetic pathways, impairment in apoptosis/autophagy and the existence of cancer stem cells. Thus, increased understanding of the mechanisms underlying cancer drug resistance suggests that an integrated approach to cancer therapy is needed for targeting multiple signaling pathways. Recent use of molecularly targeted agents to target multiple signaling pathways remains an important approach in cancer treatment; however, use of these targeted therapies is not without limitations. Further research is needed to identify approaches to repurpose drugs to optimize therapy for particular cancer types.

This Special Issue will focus on cellular targets and their mechanisms for many types of cancers, including cancer therapeutic approaches and targeted drug delivery. We are pleased to invite authors to submit contributions, such as original articles that provide novel findings, or reviews that comprehensively highlight the latest discoveries in the field.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Immune system;
  • SNC;
  • Antibodies therapies;
  • Peripheral tumors;
  • Circulating tumors;
  • Protein degradation;
  • Cell death mechanism;
  • Inflammatory pathways.

I/We look forward to receiving your contributions. 

Dr. Alessia Filippone
Dr. Marika Lanza
Guest Editors

Manuscript Submission Information

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Keywords

  • neurogenesis
  • immune evasion
  • endogenous tumor targets
  • CNS
  • neuroinflammation
  • protein degradation
  • receptors activation
  • cancerous cells invasion
  • molecular pathways

Published Papers (3 papers)

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Research

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16 pages, 4694 KiB  
Article
In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
by Gustavo H. Marin, Samuel Murail, Laura Andrini, Marcela Garcia, Severine Loisel, Pierre Tuffery and Angelita Rebollo
Pharmaceutics 2023, 15(4), 1180; https://doi.org/10.3390/pharmaceutics15041180 - 7 Apr 2023
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Abstract
The combination of a tumor-penetrating peptide (TPP) with a peptide able to interfere with a given protein–protein interaction (IP) is a promising strategy with potential clinical application. Little is known about the impact of fusing a TPP with an IP, both in terms [...] Read more.
The combination of a tumor-penetrating peptide (TPP) with a peptide able to interfere with a given protein–protein interaction (IP) is a promising strategy with potential clinical application. Little is known about the impact of fusing a TPP with an IP, both in terms of internalization and functional effect. Here, we analyze these aspects in the context of breast cancer, targeting PP2A/SET interaction, using both in silico and in vivo approaches. Our results support the fact that state-of-the-art deep learning approaches developed for protein–peptide interaction modeling can reliably identify good candidate poses for the IP-TPP in interaction with the Neuropilin-1 receptor. The association of the IP with the TPP does not seem to affect the ability of the TPP to bind to Neuropilin-1. Molecular simulation results suggest that peptide IP-GG-LinTT1 in a cleaved form interacts with Neuropilin-1 in a more stable manner and has a more helical secondary structure than the cleaved IP-GG-iRGD. Surprisingly, in silico investigations also suggest that the non-cleaved TPPs can bind the Neuropilin-1 in a stable manner. The in vivo results using xenografts models show that both bifunctional peptides resulting from the combination of the IP and either LinTT1 or iRGD are effective against tumoral growth. The peptide iRGD-IP shows the highest stability to serum proteases degradation while having the same antitumoral effect as Lin TT1-IP, which is more sensitive to proteases degradation. Our results support the development of the TPP-IP strategy as therapeutic peptides against cancer. Full article
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Review

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34 pages, 2610 KiB  
Review
Exploring Amino Acid Transporters as Therapeutic Targets for Cancer: An Examination of Inhibitor Structures, Selectivity Issues, and Discovery Approaches
by Sebastian Jakobsen and Carsten Uhd Nielsen
Pharmaceutics 2024, 16(2), 197; https://doi.org/10.3390/pharmaceutics16020197 - 30 Jan 2024
Cited by 1 | Viewed by 1894
Abstract
Amino acid transporters are abundant amongst the solute carrier family and have an important role in facilitating the transfer of amino acids across cell membranes. Because of their impact on cell nutrient distribution, they also appear to have an important role in the [...] Read more.
Amino acid transporters are abundant amongst the solute carrier family and have an important role in facilitating the transfer of amino acids across cell membranes. Because of their impact on cell nutrient distribution, they also appear to have an important role in the growth and development of cancer. Naturally, this has made amino acid transporters a novel target of interest for the development of new anticancer drugs. Many attempts have been made to develop inhibitors of amino acid transporters to slow down cancer cell growth, and some have even reached clinical trials. The purpose of this review is to help organize the available information on the efforts to discover amino acid transporter inhibitors by focusing on the amino acid transporters ASCT2 (SLC1A5), LAT1 (SLC7A5), xCT (SLC7A11), SNAT1 (SLC38A1), SNAT2 (SLC38A2), and PAT1 (SLC36A1). We discuss the function of the transporters, their implication in cancer, their known inhibitors, issues regarding selective inhibitors, and the efforts and strategies of discovering inhibitors. The goal is to encourage researchers to continue the search and development within the field of cancer treatment research targeting amino acid transporters. Full article
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23 pages, 3179 KiB  
Review
Amino Acid-Based Boron Carriers in Boron Neutron Capture Therapy (BNCT)
by Juulia Järvinen, Herkko Pulkkinen, Jarkko Rautio and Juri M. Timonen
Pharmaceutics 2023, 15(12), 2663; https://doi.org/10.3390/pharmaceutics15122663 - 23 Nov 2023
Cited by 2 | Viewed by 1568
Abstract
Interest in the design of boronated amino acids has emerged, partly due to the utilization of boronophenylalanine (BPA), one of the two agents employed in clinical Boron Neutron Capture Therapy (BNCT). The boronated amino acids synthesized thus far for BNCT investigations can be [...] Read more.
Interest in the design of boronated amino acids has emerged, partly due to the utilization of boronophenylalanine (BPA), one of the two agents employed in clinical Boron Neutron Capture Therapy (BNCT). The boronated amino acids synthesized thus far for BNCT investigations can be classified into two categories based on the source of boron: boronic acids or carboranes. Amino acid-based boron carriers, employed in the context of BNCT treatment, demonstrate significant potential in the treatment of challenging tumors, such as those located in the brain. This review aims to shed light on the developmental journey and challenges encountered over the years in the field of amino acid-based boron delivery compound development. The primary focus centers on the utilization of the large amino acid transporter 1 (LAT1) as a target for boron carriers in BNCT. The development of efficient carriers remains a critical objective, addressing challenges related to tumor specificity, effective boron delivery, and rapid clearance from normal tissue and blood. LAT1 presents an intriguing and promising target for boron delivery, given its numerous characteristics that make it well suited for drug delivery into tumor tissues, particularly in the case of brain tumors. Full article
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