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Biomolecules
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Novel Molecules for Cancer Treatment
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Novel Molecules for Cancer Treatment

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (25 June 2021) | Viewed by 25538

Special Issue Editor

Dr. Javier Martínez Useros

E-Mail Website
Guest Editor
OncoHealth Institute, Health Research Institute—Fundacion Jimenez Diaz University Hospital, Rey Juan Carlos University, 28040 Madrid, Spain
Interests: gastric cancer; pancreatic cancer; colorectal cancer and metastatic melanoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer can appear anywhere in the body, due to uncontrolled cell proliferation, inhibition of apoptosis and an increased cell migration. Tumor cells are able to activate thorough mechanisms to generate a tumor from early stages to develop metastases through the induction of angiogenesis and an immunosuppressive microenvironment. Other crucial events in tumorigenesis are the emergence of the undifferentiated phenotype and the generation and maintenance of cancer stem cells. In carcinogenesis, the co-activation of several genes and pathways is common, and the study of these factors and signaling pathways has greatly helped to identify new targets for drug design. These drugs could be chemically synthesized or isolated from natural substances. These novel molecules represent a massive step forward in reaching personalized medicine in the present clinical practice.

In this Special Issue entitled "Novel Molecules for Cancer Treatment", we encourage authors to submit high-quality research articles dealing with novel biomolecules, and provide a strong evidence of their anti-tumor potential activity to the scientific and clinical community. This activity could be observed both in solid tumors or in hematological malignancies, and be evaluated with in vitro and/or in vivo models. On the other hand, we are open to receiving updated reviews about novel molecules or treatment strategies based on synthetic or natural compounds, which could provide a rationale for further clinical oncology research.

I look forward to receiving your manuscripts.

Dr. Javier Martinez Useros
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. Biomolecules is an international peer-reviewed open access monthly 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
  • small molecules
  • antibody-drug conjugated
  • tyrosine kinases inhibitors
  • target therapy
  • monoclonal antibodies
  • immunotherapy

Published Papers (6 papers)

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Research

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16 pages, 5514 KiB  
Article
Inhibitors of Discoidin Domain Receptor (DDR) Kinases for Cancer and Inflammation
by William A. Denny and Jack U. Flanagan
Biomolecules 2021, 11(11), 1671; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11111671 - 10 Nov 2021
Cited by 8 | Viewed by 2478
Abstract
The discoidin domain receptor tyrosine kinases DDR1 and DDR2 are distinguished from other kinase enzymes by their extracellular domains, which interact with collagen rather than with peptidic growth factors, before initiating signaling via tyrosine phosphorylation. They share significant sequence and structural homology with [...] Read more.
The discoidin domain receptor tyrosine kinases DDR1 and DDR2 are distinguished from other kinase enzymes by their extracellular domains, which interact with collagen rather than with peptidic growth factors, before initiating signaling via tyrosine phosphorylation. They share significant sequence and structural homology with both the c-Kit and Bcr-Abl kinases, and so many inhibitors of those kinases are also effective. Nevertheless, there has been an extensive research effort to develop potent and specific DDR inhibitors. A key interaction for many of these compounds is H-bonding to Met-704 in a hydrophobic pocket of the DDR enzyme. The most widespread use of DDR inhibitors has been for cancer therapy, but they have also shown effectiveness in animal models of inflammatory conditions such as Alzheimer’s and Parkinson’s diseases, and in chronic renal failure and glomerulonephritis. Full article
(This article belongs to the Special Issue Novel Molecules for Cancer Treatment)
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Review

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30 pages, 2021 KiB  
Review
Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics
by Ranjith Kumavath, Sayan Paul, Honey Pavithran, Manash K. Paul, Preetam Ghosh, Debmalya Barh and Vasco Azevedo
Biomolecules 2021, 11(9), 1275; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11091275 - 25 Aug 2021
Cited by 22 | Viewed by 7217
Abstract
Cardiac glycosides are natural sterols and constitute a group of secondary metabolites isolated from plants and animals. These cardiotonic agents are well recognized and accepted in the treatment of various cardiac diseases as they can increase the rate of cardiac contractions by acting [...] Read more.
Cardiac glycosides are natural sterols and constitute a group of secondary metabolites isolated from plants and animals. These cardiotonic agents are well recognized and accepted in the treatment of various cardiac diseases as they can increase the rate of cardiac contractions by acting on the cellular sodium potassium ATPase pump. However, a growing number of recent efforts were focused on exploring the antitumor and antiviral potential of these compounds. Several reports suggest their antitumor properties and hence, today cardiac glycosides (CG) represent the most diversified naturally derived compounds strongly recommended for the treatment of various cancers. Mutated or dysregulated transcription factors have also gained prominence as potential therapeutic targets that can be selectively targeted. Thus, we have explored the recent advances in CGs mediated cancer scope and have considered various signaling pathways, molecular aberration, transcription factors (TFs), and oncogenic genes to highlight potential therapeutic targets in cancer management. Full article
(This article belongs to the Special Issue Novel Molecules for Cancer Treatment)
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19 pages, 2335 KiB  
Review
Celecoxib Analogues for Cancer Treatment: An Update on OSU-03012 and 2,5-Dimethyl-Celecoxib
by Cyril Sobolewski and Noémie Legrand
Biomolecules 2021, 11(7), 1049; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11071049 - 16 Jul 2021
Cited by 8 | Viewed by 3325
Abstract
Cyclooxygenase-2 (COX-2) is an important enzyme involved in prostaglandins biosynthesis from arachidonic acid. COX-2 is frequently overexpressed in human cancers and plays a major tumor promoting function. Accordingly, many efforts have been devoted to efficiently target the catalytic site of this enzyme in [...] Read more.
Cyclooxygenase-2 (COX-2) is an important enzyme involved in prostaglandins biosynthesis from arachidonic acid. COX-2 is frequently overexpressed in human cancers and plays a major tumor promoting function. Accordingly, many efforts have been devoted to efficiently target the catalytic site of this enzyme in cancer cells, by using COX-2 specific inhibitors such as celecoxib. However, despite their potent anti-tumor properties, the myriad of detrimental effects associated to the chronic inhibition of COX-2 in healthy tissues, has considerably limited their use in clinic. In addition, increasing evidence indicate that these anti-cancerous properties are not strictly dependent on the inhibition of the catalytic site. These findings have led to the development of non-active COX-2 inhibitors analogues aiming at preserving the antitumor effects of COX-2 inhibitors without their side effects. Among them, two celecoxib derivatives, 2,5-Dimethyl-Celecoxib and OSU-03012, have been developed and suggested for the treatment of viral (e.g., recently SARS-CoV-2), inflammatory, metabolic diseases and cancers. These molecules display stronger anti-tumor properties than celecoxib and thus may represent promising anti-cancer molecules. In this review, we discuss the impact of these two analogues on cancerous processes but also their potential for cancer treatment alone or in combination with existing approaches. Full article
(This article belongs to the Special Issue Novel Molecules for Cancer Treatment)
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17 pages, 990 KiB  
Review
Modulation of Blood–Brain Barrier Permeability by Activating Adenosine A2 Receptors in Oncological Treatment
by Kamila Wala, Wojciech Szlasa, Jolanta Saczko, Julia Rudno-Rudzińska and Julita Kulbacka
Biomolecules 2021, 11(5), 633; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11050633 - 24 Apr 2021
Cited by 11 | Viewed by 3486
Abstract
The blood–brain barrier (BBB) plays an important protective role in the central nervous system and maintains its homeostasis. It regulates transport into brain tissue and protects neurons against the toxic effects of substances circulating in the blood. However, in the case of neurological [...] Read more.
The blood–brain barrier (BBB) plays an important protective role in the central nervous system and maintains its homeostasis. It regulates transport into brain tissue and protects neurons against the toxic effects of substances circulating in the blood. However, in the case of neurological diseases or primary brain tumors, i.e., gliomas, the higher permeability of the blood-derived substances in the brain tissue is necessary. Currently applied methods of treatment for the primary brain neoplasms include surgical removal of the tumor, radiation therapy, and chemotherapy. Despite the abovementioned treatment methods, the prognosis of primary brain tumors remains bad. Moreover, chemotherapy options seem to be limited due to low drug penetration into the cancerous tissue. Modulation of the blood–brain barrier permeability may contribute to an increase in the concentration of the drug in the CNS and thus increase the effectiveness of therapy. Interestingly, endothelial cells in cerebral vessels are characterized by the presence of adenosine 2A receptors (A2AR). It has been shown that substances affecting these receptors regulate the permeability of the BBB. The mechanism of increasing the BBB permeability by A2AR agonists is the actin-cytoskeletal reorganization and acting on the tight junctions. In this case, the A2AR seems to be a promising therapy target. This article aims to assess the possibility of increasing the BBB permeability through A2AR agonists to increase the effectiveness of chemotherapy and to improve the results of cancer therapy. Full article
(This article belongs to the Special Issue Novel Molecules for Cancer Treatment)
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12 pages, 687 KiB  
Review
The Controversial Role of Autophagy in Ewing Sarcoma Pathogenesis—Current Treatment Options
by Evangelos Koustas, Panagiotis Sarantis, Michalis V. Karamouzis, Philippe Vielh and Stamatios Theocharis
Biomolecules 2021, 11(3), 355; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11030355 - 26 Feb 2021
Cited by 8 | Viewed by 2190
Abstract
Ewing Sarcoma (ES) is a rare, aggressive, and highly metastasizing cancer in children and young adults. Most ES cases carry the fusion of the Ewing Sarcoma Breakpoint Region 1 (EWSR1) and FLI1 (Friend leukemia virus integration site 1) genes, leading to [...] Read more.
Ewing Sarcoma (ES) is a rare, aggressive, and highly metastasizing cancer in children and young adults. Most ES cases carry the fusion of the Ewing Sarcoma Breakpoint Region 1 (EWSR1) and FLI1 (Friend leukemia virus integration site 1) genes, leading to an EWS–FLI1 fused protein, which is associated with autophagy, a homeostatic and catabolic mechanism under normal and pathological conditions. Following such interesting and controversial data regarding autophagy in ES, many clinical trials using modulators of autophagy are now underway in this field. In the present review, we summarize current data and clinical trials that associate autophagy with ES. In vitro studies highlight the controversial role of autophagy as a tumor promoter or a tumor suppressor mechanism in ES. Clinical and in vitro studies on ES, together with the autophagy modulators, suggest that caution should be adopted in the application of autophagy as a therapeutic target. Monitoring and targeting autophagy in every ES patient could eliminate the need for targeting multiple pathways in order to achieve the maximum beneficial effect. Future studies are required to focus on which ES patients are affected by autophagy modulators in order to provide novel and more efficient therapeutic protocols for patients with ES based on the current autophagy status of the tumors. Full article
(This article belongs to the Special Issue Novel Molecules for Cancer Treatment)
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26 pages, 1646 KiB  
Review
Carotenoids in Cancer Metastasis—Status Quo and Outlook
by Lenka Koklesova, Alena Liskova, Marek Samec, Kevin Zhai, Mariam Abotaleb, Milad Ashrafizadeh, Aranka Brockmueller, Mehdi Shakibaei, Kamil Biringer, Ondrej Bugos, Masoud Najafi, Olga Golubnitschaja, Dietrich Büsselberg and Peter Kubatka
Biomolecules 2020, 10(12), 1653; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10121653 - 10 Dec 2020
Cited by 30 | Viewed by 5499
Abstract
Metastasis represents a major obstacle in cancer treatment and the leading cause of cancer-related deaths. Therefore, the identification of compounds targeting the multi-step and complex process of metastasis could improve outcomes in the management of cancer patients. Carotenoids are naturally occurring pigments with [...] Read more.
Metastasis represents a major obstacle in cancer treatment and the leading cause of cancer-related deaths. Therefore, the identification of compounds targeting the multi-step and complex process of metastasis could improve outcomes in the management of cancer patients. Carotenoids are naturally occurring pigments with a plethora of biological activities. Carotenoids exert a potent anti-cancer capacity in various cancer models in vitro and in vivo, mediated by the modulation of signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of the epithelial–mesenchymal transition and regulatory molecules, such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), urokinase plasminogen activator (uPA) and its receptor (uPAR), hypoxia-inducible factor-1α (HIF-1α), and others. Moreover, carotenoids modulate the expression of genes associated with cancer progression and inflammatory processes as key mediators of the complex process involved in metastasis. Nevertheless, due to the predominantly preclinical nature of the known anti-tumor effects of carotenoids, and unclear results from certain carotenoids in specific cancer types and/or specific parts of the population, a precise analysis of the anti-cancer effects of carotenoids is essential. The identification of carotenoids as effective compounds targeting the complex process of cancer progression could improve the outcomes of advanced cancer patients. Full article
(This article belongs to the Special Issue Novel Molecules for Cancer Treatment)
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