Special Issue "Kinase Signaling and Kinase Targeted Therapies on Cancer: Advances, Challenges, and Future Direction"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 2041

Special Issue Editor

Prof. Dr. Valentina De Falco
E-Mail Website
Guest Editor
Institute Experimental Endocrinology and Oncology IEOS/CNR, Università degli Studi di Napoli Federico II, Naples, Italy
Interests: Cancer; Kinase inhibitor; Target therapy; Signal transduction; Cell cycle; Mitogenesis; Survival; Resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Transferring γ-phosphate onto diverse substrates enables kinases to regulate key cellular functions. As many human diseases result from the mutation and overexpression of kinases, targeting of this enzyme class symbolizes an important strategy for drug development. Many of these kinases are associated with human cancer initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Kinase inhibitors represent targeted therapy resulting from the understanding of molecular genetics and molecular signaling pathways. This class of therapeutics represents a transformation from conventional chemotherapy to targeted cancer treatment. Nevertheless, many factors confound the clinical efficacy of these molecules. Specific tumor genetics, tumor microenvironment, drug resistance, and pharmacogenomics determine how useful a compound will be in the treatment of a given cancer. Due to the clinical importance of kinase inhibitors, multiple strategies are required to overcome resistance mechanisms and develop more effective targeted therapies. Moreover, kinase inhibitors are not only important for the treatment of cancer but also help us better understand the physiological roles of kinases. This Special Issue intends to serve as a compilation overviewing kinase signaling and kinase-targeted drug discovery and development in relation to oncology and highlighting the challenges and future potential for kinase-targeted cancer therapies.

Prof. Dr. Valentina De Falco
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. Cells 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 2200 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
  • oncogene
  • kinase inhibitors
  • tumor drug resistance
  • signal transduction
  • survival
  • cell reprogramming
  • target therapy
  • cancer heterogeneity
  • biomarkers

Published Papers (2 papers)

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

Research

Jump to: Review

Article
The Influence of PARP, ATR, CHK1 Inhibitors on Premature Mitotic Entry and Genomic Instability in High-Grade Serous BRCAMUT and BRCAWT Ovarian Cancer Cells
Cells 2022, 11(12), 1889; https://doi.org/10.3390/cells11121889 - 10 Jun 2022
Viewed by 720
Abstract
Olaparib is a poly (ADP-ribose) polymerase inhibitor (PARPi) that inhibits PARP1/2, leading to replication-induced DNA damage that requires homologous recombination repair. Olaparib is often insufficient to treat BRCA-mutated (BRCAMUT) and BRCA wild-type (BRCAWT) high-grade serous ovarian [...] Read more.
Olaparib is a poly (ADP-ribose) polymerase inhibitor (PARPi) that inhibits PARP1/2, leading to replication-induced DNA damage that requires homologous recombination repair. Olaparib is often insufficient to treat BRCA-mutated (BRCAMUT) and BRCA wild-type (BRCAWT) high-grade serous ovarian carcinomas (HGSOCs). We examined the short-term (up to 48 h) efficacy of PARPi treatment on a DNA damage response pathway mediated by ATR and CHK1 kinases in BRCAMUT (PEO-1) and BRCAWT (SKOV-3 and OV-90) cells. The combination of ATRi/CHK1i with PARPi was not more cytotoxic than ATR and CHK1 monotherapy. The combination of olaparib with inhibitors of the ATR/CHK1 pathway generated chromosomal abnormalities, independent on BRCAMUT status of cells and formed of micronuclei (MN). However, the beneficial effect of the PARPi:ATRi combination on MN was seen only in the PEO1 BRCAMUT line. Monotherapy with ATR/CHK1 inhibitors reduced BrdU incorporation due to a slower rate of DNA synthesis, which resulted from elevated levels of replication stress, while simultaneous blockade of PARP and ATR caused beneficial effects only in OV-90 cells. Inhibition of ATR/CHK1 increased the formation of double-strand breaks as measured by increased γH2AX expression at collapsed replication forks, resulting in increased levels of apoptosis. Our findings indicate that ATR and CHK1 inhibitors provoke premature mitotic entry, leading to genomic instability and ultimately cell death. Full article
Show Figures

Figure 1

Review

Jump to: Research

Review
Ibrutinib in the Treatment of Solid Tumors: Current State of Knowledge and Future Directions
Cells 2022, 11(8), 1338; https://doi.org/10.3390/cells11081338 - 14 Apr 2022
Cited by 2 | Viewed by 838
Abstract
Bruton’s Tyrosine Kinase (BTK) is considered crucial in the activation and survival of both physiological and malignant B-cells. In recent years, ibrutinib, an oral BTK inhibitor, became a breakthrough therapy for hematological malignancies, such as chronic lymphocytic. However, ibrutinib’s feasibility might not end [...] Read more.
Bruton’s Tyrosine Kinase (BTK) is considered crucial in the activation and survival of both physiological and malignant B-cells. In recent years, ibrutinib, an oral BTK inhibitor, became a breakthrough therapy for hematological malignancies, such as chronic lymphocytic. However, ibrutinib’s feasibility might not end there. Several other kinases with established involvement with solid malignancies (i.e., EGFR, HER2) have been found to be inhibited by this agent. Recent discoveries indicate that BTK is a potential anti-solid tumor therapy target. Consequently, ibrutinib, a BTK-inhibitor, has been studied as a therapeutic option in solid malignancies. While most preclinical studies indicate ibrutinib to be an effective therapeutic option in some specific indications, such as NSCLC and breast cancer, clinical trials contradict these observations. Nevertheless, while ibrutinib failed as a monotherapy, it might become an interesting part of a multidrug regime: not only has a synergism between ibrutinib and other compounds, such as trametinib or dactolisib, been observed in vitro, but this BTK inhibitor has also been established as a radio- and chemosensitizer. This review aims to describe the milestones in translating BTK inhibitors to solid tumors in order to understand the future potential of this agent better. Full article
Show Figures

Figure 1

Back to TopTop