Special Issue "The Role of Src Kinase Family in Cancer"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 May 2020).

Special Issue Editor

Prof. Dr. Silvia Schenone
Website
Guest Editor
Department of Pharmacy, Università degli Studi di Genova, 16126 Genova, Italy
Interests: cancer; tyrosine kinases; serine-threonine kinases; kinase inhibitors; small molecules; organic synthesis; ADME studies; drug formulations
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Special Issue Information

Dear Colleagues,

The involvement of many tyrosine kinases in cancers has been strongly demonstrated. These enzymes include receptor or transmembrane kinases and cytoplasmic or non-receptor kinases. Src family kinases (SFKs) are the biggest class of non-receptor tyrosine kinases, and consist of nine highly homologous members.

SFKs regulate multiple signal transduction pathways which are involved in cell growth, proliferation, differentiation, migration, and apoptosis, in addition to playing important roles in angiogenesis. All these functions are altered in cancer. It has been widely demonstrated that while SFK activities are strictly regulated in healthy cells, some SFK members are overexpressed and/or hyperactivated in many solid and hematological cancers and are promoting factors for the development of metastatic cancer phenotypes.

Many biological roles have been demonstrated for SFKs. Src, which was the first SFK identified and is the most-studied enzyme belonging to this family, provides a well-known case-in-point.

The Src inhibitors dasatinib, bosutinib, and ponatinib, which also target other similar kinases, have been approved for chronic myeloid leukemia treatment, while other compounds, including saracatinib, are in clinical trials for their potential applications in many tumors. Other SFK inhibitors are being developed and are in preclinical studies.

This Special Issue is devoted to investigations that highlight further roles played by SFKs in cancer development, and studies that will lead to new potentially useful SFK inhibitors that could improve specific anticancer therapies.

Prof. Dr. Silvia Schenone
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 papers will be 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. Cancers 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 2000 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

  • Src family kinases
  • cell pathways
  • cancer therapy
  • kinase inhibitors

Published Papers (3 papers)

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Research

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Open AccessArticle
The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma
Cancers 2019, 11(11), 1644; https://doi.org/10.3390/cancers11111644 - 25 Oct 2019
Abstract
Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage [...] Read more.
Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage solid tumors, including head and neck squamous cell carcinomas (HNSCC). Adequate selection and stratification of patients who may respond to and benefit from anti-SRC therapies is therefore needed to guide clinical trials and treatment efficacy. This study investigates the prognostic significance of active SRC expression in a homogeneous cohort of 122 human papillomavirus (HPV)-negative, surgically treated HNSCC patients. Immunohistochemical evaluation of the active form of SRC by means of anti-SRC Clone 28 monoclonal antibody was specifically performed and subsequently correlated with clinical data. The expression of p-SRC (Tyr419), total SRC, and downstream SRC effectors was also analyzed. Our results uncovered striking differences in the prognostic relevance of SRC expression in HNSCC patients depending on the tumor site. Active SRC expression was found to significantly associate with advanced disease stages, presence of lymph node metastasis, and tumor recurrences in patients with laryngeal tumors, but not in the pharyngeal subgroup. Multivariate Cox analysis further revealed active SRC expression as an independent predictor of cancer-specific mortality in patients with laryngeal carcinomas. Concordantly, expression of p-SRC (Tyr419) and the SRC substrates focal adhesion kinase (FAK) and the Arf GTPase-activating protein ASAP1 also showed specific associations with poor prognosis in the larynx. These findings could have important implications in ongoing Src family kinase (SFK)-based clinical trials, as these new criteria could help to improve patient selection and develop biomarker-stratified trials. Full article
(This article belongs to the Special Issue The Role of Src Kinase Family in Cancer)
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Review

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Open AccessReview
The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)
Cancers 2020, 12(6), 1361; https://doi.org/10.3390/cancers12061361 (registering DOI) - 26 May 2020
Abstract
The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because [...] Read more.
The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src–YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted. Full article
(This article belongs to the Special Issue The Role of Src Kinase Family in Cancer)
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Open AccessReview
Regulation of Src Family Kinases during Colorectal Cancer Development and Its Clinical Implications
Cancers 2020, 12(5), 1339; https://doi.org/10.3390/cancers12051339 - 23 May 2020
Abstract
Src family kinases (SFKs) are non-receptor kinases that play a critical role in the pathogenesis of colorectal cancer (CRC). The expression and activity of SFKs are upregulated in patients with CRC. Activation of SFKs promotes CRC cell proliferation, metastases to other organs and [...] Read more.
Src family kinases (SFKs) are non-receptor kinases that play a critical role in the pathogenesis of colorectal cancer (CRC). The expression and activity of SFKs are upregulated in patients with CRC. Activation of SFKs promotes CRC cell proliferation, metastases to other organs and chemoresistance, as well as the formation of cancer stem cells (CSCs). The enhanced expression level of Src is associated with decreased survival in patients with CRC. Src-mediated regulation of CRC progression involves various membrane receptors, modulators, and suppressors, which regulate Src activation and its downstream targets through various mechanisms. This review provides an overview of the current understanding of the correlations between Src and CRC progression, with a special focus on cancer cell proliferation, invasion, metastasis and chemoresistance, and formation of CSCs. Additionally, this review discusses preclinical and clinical strategies to improve the therapeutic efficacy of drugs targeting Src for treating patients with CRC. Full article
(This article belongs to the Special Issue The Role of Src Kinase Family in Cancer)
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