Special Issue "The Role of Autophagy in Cancer Progression and Drug Resistance"

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

Deadline for manuscript submissions: 30 September 2019

Special Issue Editor

Guest Editor
Dr. Steffan T. Nawrocki

Department of Medicine, Division of Translational and Regenerative Medicine, University of Arizona Cancer Center, Tucson, AZ 85724, USA
Website | E-Mail
Interests: autophagy, experimental cancer therapeutics, oncolytic virus therapy, endoplasmic reticular stress, anticancer drug resistance

Special Issue Information

Dear Colleagues,

Autophagy is an evolutionarily conserved lysosome-mediated protein degradation process that functions to turnover organelles and proteins with long half-lives. This role of autophagy suppresses tumor formation via the elimination of defective pre-malignant cells and maintains bioenergetic homeostasis under stress conditions including hypoxia and nutrient deprivation. However, autophagy may also promote cancer progression and drug resistance in established diseases via the generation of alternative sources of energy through nutrient recycling. Despite having diverse mechanisms of action, many frontline anticancer agents ultimately shut down conventional metabolic pathways because of the cellular stress that they impose and, thus, stimulate autophagy. Importantly, pharmacological or genetic inhibition of autophagy significantly enhances the anticancer activity of many different forms of cancer therapeutics. On the basis of these collective findings, it appears that inhibition of autophagy is a promising novel approach with broad applications in cancer therapy. We welcome articles focused on autophagy and its roles in cancer progression and drug resistance.

Dr. Steffan T. Nawrocki
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 1800 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

  • autophagy
  • lysosome
  • protein degradation
  • drug resistance
  • cancer
  • cell survival
  • cell metabolism
  • mTOR
  • combination therapy

Published Papers (1 paper)

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Research

Open AccessArticle Immunohistochemical Expression of Autophagy-Related Proteins in Advanced Tubular Gastric Adenocarcinomas and Its Implications
Cancers 2019, 11(3), 389; https://doi.org/10.3390/cancers11030389
Received: 25 February 2019 / Revised: 13 March 2019 / Accepted: 15 March 2019 / Published: 19 March 2019
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Abstract
In neoplastic conditions, autophagy may act as a tumor suppressor avoiding the accumulation of damaged proteins and organelles or as a mechanism of cell survival promoting the tumor growth. Although ultrastructural analysis has been considered the traditional method to identify autophagy, some proteins [...] Read more.
In neoplastic conditions, autophagy may act as a tumor suppressor avoiding the accumulation of damaged proteins and organelles or as a mechanism of cell survival promoting the tumor growth. Although ultrastructural analysis has been considered the traditional method to identify autophagy, some proteins such as microtubule-associated protein 1 light chain 3 (LC3A/B), Beclin-1 and activating molecule in Beclin-1-regulated autophagy protein-1 (AMBRA-1) may be considered as markers of autophagy-assisted cancerogenesis. Herein, we analyzed a cohort of advanced tubular gastric adenocarcinomas by the abovementioned immunohistochemical antisera; through immunohistochemistry, autophagy (A-IHC) is diagnosed when at least two out of the three proteins are positive in the samples. Immunostaining for LC3A/B, Beclin-1, and AMBRA-1 was exclusively found in neoplastic elements, but not in surrounding stromal cells. In detail, LC3A/B and Beclin 1 were expressed both in the cytoplasm and in the nucleus of the cancer cells, while AMBRA-1 was preferentially localized in the nucleus, mainly in high grade cases. LC3A/B, Beclin 1, and AMBRA-1 expression were positive in 18 (56.2%), 17 (53.1%), and 12 (37.5%) cases, respectively. The sensibility and specificity of LC3A/B and Beclin-1 ranged from 81.25% to 93.75%, with high efficiency (90.63%) for Beclin-1. Moreover, the ultrastructural autophagic index (AI) was also available in all cases. All high-grade cases documented a Ki-67 labelling index (LI) ≥ 30%, even if three low-grade cases revealed a high Ki-67 value; p53 positivity was encountered in 21/32 (65.62%) of cases, independently of the tumor grade. A statistically significant correlation among A-IHC and clinicopathological parameters such as grade, stage, clinical course, Ki-67 LI and AI was revealed. Univariate analysis documented a significant p-value for the same autophagic variables. Additionally, multivariate survival analysis identified the grade, AI and A-IHC as independent significant variables. Finally, the overall survival curves of all cases of gastric tubular adenocarcinoma were greatly dependent on A-IHC. Therefore, we suggest that autophagic-related proteins might be considered promising predictive prognostic factors of advanced gastric cancer. Further investigations may be required to determine whether new targeted therapies should be addressed to autophagy-related proteins. Full article
(This article belongs to the Special Issue The Role of Autophagy in Cancer Progression and Drug Resistance)
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