Cancer Mechanisms and Emerging Therapies

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

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 21904

Special Issue Editors


E-Mail Website
Guest Editor
Research Center for Advanced Medicine-Medfuture, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
Interests: oncology; experimental therapy; molecular biology; genomics; transcriptomics; epigenetics

E-Mail Website
Guest Editor
Research Center for Advanced Medicine-Medfuture, Department of Pharmaceutical Analysis, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
Interests: pharmaceutics; proteomics; metabolomics; biomarkers discovery and validation

Special Issue Information

Dear Colleagues,

We are pleased to announce the new Special Issue for Pharmaceutics entitled “Cancer Mechanisms and Emerging Therapies”.

Solid and haematological malignancies are currently in the front row of research and innovation due to the intense burden of these pathologies on the society at multiple levels. The oncology sector has evolved greatly from the standard chemotherapeutic agents to the novel immunotherapeutic formulations, targeted antibodies, gene editing, epigenetic agents and others, concomitant with the delivery formulations with improved targeting and concentration to the tumour site. At the base of these latest therapies are the biochemical and signalling processes that are aberrantly conducted in cancer cells, concomitant with a pathological communication with the surrounding microenvironment. The therapeutic intervention is meant to disrupt the pathological signalling or impair the favouring cancer associated cells and mechanisms that are encountered in the microenvironment.

The Special Issue is meant to highlight the latest translational research in oncology, starting with new identified oncogenic or tumour suppressor mechanisms (within cancer cells or microenvironment) that are enabling the carcinogenesis process and also the current progress in therapeutic schemes and formulations that are meant to disrupt the above mechanisms.

Dr. Diana Gulei
Prof. Dr. Cristina Adela Iuga
Guest Editors

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. Pharmaceutics 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 2900 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

  • oncology
  • cancer mechanisms
  • therapy
  • cancer microenvironment
  • translational research
  • drug formulations and design

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

3 pages, 184 KiB  
Editorial
Cancer Mechanisms and Emerging Therapies
by Diana Gulei, Alice Indini, Carmen Jerónimo, Cristina-Adela Iuga and Francesco Grossi
Pharmaceutics 2021, 13(7), 1045; https://doi.org/10.3390/pharmaceutics13071045 - 9 Jul 2021
Viewed by 2071
Abstract
Over the last decades, cancer has become one of the most relevant health issues at a worldwide level [...] Full article
(This article belongs to the Special Issue Cancer Mechanisms and Emerging Therapies)

Research

Jump to: Editorial, Review

20 pages, 4392 KiB  
Article
Hsa-miR-125b Therapeutic Role in Colon Cancer Is Dependent on the Mutation Status of the TP53 Gene
by Diana Cenariu, Alina-Andreea Zimta, Raluca Munteanu, Anca Onaciu, Cristian Silviu Moldovan, Ancuta Jurj, Lajos Raduly, Alin Moldovan, Adrian Florea, Liviuta Budisan, Laura Ancuta Pop, Lorand Magdo, Mihai Tudor Albu, Rares Bogdan Tonea, Mihai-Stefan Muresan, Calin Ionescu, Bogdan Petrut, Rares Buiga, Alexandru Irimie, Diana Gulei and Ioana Berindan-Neagoeadd Show full author list remove Hide full author list
Pharmaceutics 2021, 13(5), 664; https://doi.org/10.3390/pharmaceutics13050664 - 6 May 2021
Cited by 6 | Viewed by 3090
Abstract
Colon cancer is the third most common cancer type worldwide and is highly dependent on DNA mutations that progressively appear and accumulate in the normal colon epithelium. Mutations in the TP53 gene appear in approximately half of these patients and have significant implications [...] Read more.
Colon cancer is the third most common cancer type worldwide and is highly dependent on DNA mutations that progressively appear and accumulate in the normal colon epithelium. Mutations in the TP53 gene appear in approximately half of these patients and have significant implications in disease progression and response to therapy. miR-125b-5p is a controversial microRNA with a dual role in cancer that has been reported to target specifically TP53 in colon adenocarcinomas. Our study investigated the differential therapeutic effect of miR-125b-5p replacement in colon cancer based on the TP53 mutation status of colon cancer cell lines. In TP53 mutated models, miR-125b-5p overexpression slows cancer cells’ malignant behavior by inhibiting the invasion/migration and colony formation capacity via direct downregulation of mutated TP53. In TP53 wild type cells, the exogenous modulation of miR-125b-5p did not significantly affect the molecular and phenotypic profile. In conclusion, our data show that miR-125b-5p has an anti-cancer effect only in TP53 mutated colon cancer cells, explaining partially the dual behavior of this microRNA in malignant pathologies. Full article
(This article belongs to the Special Issue Cancer Mechanisms and Emerging Therapies)
Show Figures

Figure 1

17 pages, 2887 KiB  
Article
Affibody-Derived Drug Conjugates Targeting HER2: Effect of Drug Load on Cytotoxicity and Biodistribution
by Haozhong Ding, Tianqi Xu, Jie Zhang, Vladimir Tolmachev, Maryam Oroujeni, Anna Orlova, Torbjörn Gräslund and Anzhelika Vorobyeva
Pharmaceutics 2021, 13(3), 430; https://doi.org/10.3390/pharmaceutics13030430 - 23 Mar 2021
Cited by 12 | Viewed by 3708
Abstract
Affibody molecules hold great promise as carriers of cytotoxic drugs for cancer therapy due to their typically high affinity, easy production, and inherent control of the drug molecules’ loading and spatial arrangement. Here, the impact of increasing the drug load from one to [...] Read more.
Affibody molecules hold great promise as carriers of cytotoxic drugs for cancer therapy due to their typically high affinity, easy production, and inherent control of the drug molecules’ loading and spatial arrangement. Here, the impact of increasing the drug load from one to three on the properties of an affibody drug conjugate targeting the human epidermal growth factor receptor 2 (HER2) was investigated. The affibody carrier was recombinantly expressed as a fusion to an albumin-binding domain (ABD) for plasma half-life extension. One or three cysteine amino acids were placed at the C-terminus to which cytotoxic mcDM1 molecules were conjugated. The resulting drug conjugates, ZHER2–ABD–mcDM1 and ZHER2–ABD–mcDM13, were characterized in vitro, and their biodistribution in mice carrying HER2-overexpressing SKOV3 xenografts was determined. Increasing the drug load from one to three led to a decrease in affinity for HER2, but a significantly more potent cytotoxic effect on SKOV3 cells with high HER2 expression. The difference in cytotoxic effect on other cell lines with high HER2 expression was not significant. In vivo, an increase in drug load led to a 1.45-fold higher amount of cytotoxic mcDM1 delivered to the tumors. The increase in drug load also led to more rapid hepatic clearance, warranting further optimization of the molecular design. Full article
(This article belongs to the Special Issue Cancer Mechanisms and Emerging Therapies)
Show Figures

Graphical abstract

18 pages, 4806 KiB  
Article
Targeting Germ Cell Tumors with the Newly Synthesized Flavanone-Derived Compound MLo1302 Efficiently Reduces Tumor Cell Viability and Induces Apoptosis and Cell Cycle Arrest
by João Lobo, Ana Rita Cardoso, Vera Miranda-Gonçalves, Leendert H. J. Looijenga, Marie Lopez, Paola B. Arimondo, Rui Henrique and Carmen Jerónimo
Pharmaceutics 2021, 13(1), 73; https://doi.org/10.3390/pharmaceutics13010073 - 7 Jan 2021
Cited by 12 | Viewed by 2873
Abstract
Less toxic treatment strategies for testicular germ cell tumor (TGCT) patients are needed, as overtreatment is a concern due to the long-term side effects of platin-based chemotherapy. Although clinical benefit from classical hypomethylating agents has to date been limited, TGCTs show an abnormal [...] Read more.
Less toxic treatment strategies for testicular germ cell tumor (TGCT) patients are needed, as overtreatment is a concern due to the long-term side effects of platin-based chemotherapy. Although clinical benefit from classical hypomethylating agents has to date been limited, TGCTs show an abnormal DNA methylome indicating the potential of treating TGCTs with hypomethylating drugs. We tested, for the first time in TGCT cell lines, a new synthetic flavonoid compound (MLo1302) from the 3-nitroflavanone family of DNA methyltransferase (DNMT) inhibitors. We show that MLo1302 reduces cell viability (including of cisplatin resistant cell line NCCIT-R), with IC50s (inhibitory concentration 50) within the nanomolar range for NCCIT and NTERA-2 cells, and proved its cytotoxic effect. Exposure to MLo1302 reduced DNMT protein expression, similar to decitabine, and showed a partial effect in cell differentiation, reducing protein expression of pluripotency markers. RT2 profiler expression array indicated several dysregulated targets, related to activation of apoptosis, differentiation, and cell cycle arrest. We validated these data by showing increased apoptosis, increased protein expression of cleaved caspase 8 and activated caspase 2, and reduced proliferation (BrdU assay), with increase in CDKN1A and decrease in MIB-1 expression. Therefore, synthetic drugs designed to target DNA methylation in cells may uncover effective treatments for TGCT patients. Full article
(This article belongs to the Special Issue Cancer Mechanisms and Emerging Therapies)
Show Figures

Graphical abstract

Review

Jump to: Editorial, Research

17 pages, 674 KiB  
Review
Targeting KRAS in Solid Tumors: Current Challenges and Future Opportunities of Novel KRAS Inhibitors
by Alice Indini, Erika Rijavec, Michele Ghidini, Alessio Cortellini and Francesco Grossi
Pharmaceutics 2021, 13(5), 653; https://doi.org/10.3390/pharmaceutics13050653 - 4 May 2021
Cited by 31 | Viewed by 5917
Abstract
Activating mutations in RAS family proteins are found in ~25% of all human cancers. Different solid tumors are correlated with mutations in certain isoforms of RAS, with Kirsten RAS (KRAS) being the most frequently mutated isoform. Historically, KRAS has been acknowledged as “undruggable”, [...] Read more.
Activating mutations in RAS family proteins are found in ~25% of all human cancers. Different solid tumors are correlated with mutations in certain isoforms of RAS, with Kirsten RAS (KRAS) being the most frequently mutated isoform. Historically, KRAS has been acknowledged as “undruggable”, largely because the RAS proteins do not appear to present suitable pockets to which small inhibitory molecules can bind. However, this scenario has changed over the last years with the advent of novel KRAS inhibitors. In this review, we describe the role of KRAS mutation across different solid tumors, providing data on novel KRAS inhibitors currently under development and an updated overview of ongoing research in this field. A literature search was performed to select papers, abstracts, and oral presentation on KRAS inhibitory strategies in KRAS mutated solid tumors. Overall, the most promising therapeutic results have been obtained with molecules targeting KRAS G12C, thus paving the way for a significant therapeutic improvement in non-small cell lung cancer. Unfortunately, KRAS G12C mutation is rather uncommon in other solid tumors, namely pancreatic ductal adenocarcinoma and colorectal cancer. Several combination strategies are currently under evaluation in clinical trials, in order to bypass the resistance mechanisms responsible for the intrinsic resistance of mutated KRAS to the main therapeutic strategies adopted to date. Results suggest that the therapeutic scenario of KRAS has started to change, and further research will bring therapeutic results in this field. Full article
(This article belongs to the Special Issue Cancer Mechanisms and Emerging Therapies)
Show Figures

Figure 1

19 pages, 2100 KiB  
Review
Biological Therapy with Complementary and Alternative Medicine in Innocuous Integrative Oncology: A Case of Cervical Cancer
by Elvin Peter Chizenga and Heidi Abrahamse
Pharmaceutics 2021, 13(5), 626; https://doi.org/10.3390/pharmaceutics13050626 - 28 Apr 2021
Cited by 5 | Viewed by 3253
Abstract
Good medicine is based on good science, inquiry driven and open to new paradigms. For a complex disease such as cancer, a complex treatment regime that is well structured and multifactorial is indispensable. In the present day, Complementary and Alternative Medicine (CAM) therapies [...] Read more.
Good medicine is based on good science, inquiry driven and open to new paradigms. For a complex disease such as cancer, a complex treatment regime that is well structured and multifactorial is indispensable. In the present day, Complementary and Alternative Medicine (CAM) therapies are being used frequently for cancer, alongside modern biological therapies and allopathic medicine, in what is called integrative oncology. In all conscience, the use of natural, less invasive interventions whenever possible is ideal. However, a comprehensive understanding of not only the etiopathology of individual cancers, but also the detailed genetic and epigenetic characteristics, the cancer hallmarks, that clearly show the blueprint of the cancer phenotype is a requisite. Different tumors have a common behavioral pattern, but their specific features at the genetic and epigenetic levels vary to a great extent. Henceforth, with so many failed attempts to therapy, drug formulations and combinations need a focused pre-assessment of the inherent features of individual cancers to destroy the tumors holistically by targeting these features. This review therefore presents innocuous therapeutic regimes by means of CAM and integrative medicine approaches that can specifically target the hallmarks of cancer, using the case of cervical cancer. Full article
(This article belongs to the Special Issue Cancer Mechanisms and Emerging Therapies)
Show Figures

Graphical abstract

Back to TopTop