Special Issue "Cancer Cachexia"

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

Deadline for manuscript submissions: 31 July 2019

Special Issue Editors

Guest Editor
Dr. Teresa A. Zimmers

Department of Surgery, Indiana University School of Medicine; Indiana University Purdue University Indianapolis Center for Cachexia Research, Innovation, and Therapy; Indiana University Simon Cancer Center; Richard Roudebush VAMC. IN USA
Website | E-Mail
Interests: pancreatic cancer; muscle atrophy; cancer cachexia; symptom science; cancer metabolism
Guest Editor
Dr. Richard Skipworth

Clinical Surgery, University of Edinburgh, Royal infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, United Kingdom
Website | E-Mail
Interests: cancer cachexia; muscle wasting; esophagogastric cancer; surgery; clinical trials

Special Issue Information

Dear Colleagues,

Cachexia is an underappreciated cause of cancer patient morbidity and mortality. It is associated with an impaired response to treatment, increased risk of treatment-related complications, decreased quality of life, and shortened survival. Key clinical components of the cachexia syndrome include wasting of peripheral tissues (namely, skeletal muscle and adipose tissue), primary anorexia, alterations in circulating neuroendocrine hormones, and induction of a systemic inflammatory response. Cachexia is driven by tumor-derived mediators that signal to disrupt host immunity and metabolism. Much progress has been made in the past 20 years in identifying molecular and cellular mediators of cancer cachexia. Major questions remain, however, particularly in understanding tumor–organ crosstalk, in identifying key nodes upstream of known cytokine cascades and inflammation, and in defining targetable end organ responses to cachexia-causing tumors. Additionally, understanding the link between metabolic dysregulation of cachexia and immune suppression could improve the efficacy of immunotherapy.

Despite increased understanding of pathological mechanisms of cachexia and a considerable uptick in anticachexia trials, there is still no effective approved therapy that can prevent or reverse cancer cachexia. Although certain ghrelin analogs and selective androgen receptor modulators have shown to be beneficial in terms of increasing patient lean body mass, these trials have been unable to demonstrate an associated gain in patient functional status. Trial methodology has improved with consensus definitions for clinical cachexia and the use of body composition analysis via diagnostic imaging modalities. However, further improvements in trial methodology, including the identification of early biomarkers, the accommodation of multimodal treatment regimens, and the development of robust coprimary endpoints, are required.

This Special Issue of Cancers will highlight the current state-of-the-art in cachexia biology and develop our understanding of the complexity of this syndrome. Research articles and review articles reporting basic science, translational studies, and clinical studies are all encouraged.

Dr. Teresa A. Zimmers
Dr. Richard Skipworth
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 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.

Published Papers (2 papers)

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Research

Open AccessArticle Chronic Treatment with Multi-Kinase Inhibitors Causes Differential Toxicities on Skeletal and Cardiac Muscles
Cancers 2019, 11(4), 571; https://doi.org/10.3390/cancers11040571 (registering DOI)
Received: 14 February 2019 / Revised: 12 April 2019 / Accepted: 18 April 2019 / Published: 23 April 2019
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Abstract
Despite recent progress, chemotherapy remains the preferred treatment for cancer. We have shown a link between anticancer drugs and the development of cachexia, i.e., body wasting accompanied by muscle loss. The multi-kinase inhibitors (MKIs) regorafenib and sorafenib, used as second-line treatment for solid [...] Read more.
Despite recent progress, chemotherapy remains the preferred treatment for cancer. We have shown a link between anticancer drugs and the development of cachexia, i.e., body wasting accompanied by muscle loss. The multi-kinase inhibitors (MKIs) regorafenib and sorafenib, used as second-line treatment for solid tumors, are frequently accompanied by several side effects, including loss of muscle mass and strength. In the present study we aimed to investigate the molecular mechanisms associated with the occurrence of muscle toxicities in in vivo conditions. Hence, we treated 8-week old healthy CD2F1 male mice with MKIs for up to six weeks and observed decreased skeletal and cardiac muscle mass, consistent with muscle weakness. Modulation of ERK1/2 and GSK3β, as well as increased expression of markers of autophagy, previously associated with muscle atrophy conditions, were shown in skeletal muscle upon treatment with either drug. MKIs also promoted cardiac abnormalities consistent with reduced left ventricular mass, internal diameter, posterior wall thickness and stroke volume, despite unchanged overall function. Notably, different signaling pathways were affected in the heart, including reduced expression of mitochondrial proteins, and elevated AKT, GSK3β, mTOR, MEK1/2 and ERK1/2 phosphorylation. Combined, our data demonstrate detrimental effects on skeletal and cardiac muscle in association with chronic administration of MKIs, although different mechanisms would seem to contribute to the cachectic phenotype in the two tissues. Full article
(This article belongs to the Special Issue Cancer Cachexia)
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Open AccessArticle Moderate Exercise Improves Experimental Cancer Cachexia by Modulating the Redox Homeostasis
Cancers 2019, 11(3), 285; https://doi.org/10.3390/cancers11030285
Received: 27 January 2019 / Revised: 20 February 2019 / Accepted: 23 February 2019 / Published: 28 February 2019
PDF Full-text (4291 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cachexia is a debilitating syndrome that complicates the management of cancer patients. Muscle wasting, one of the main features of cachexia, is associated with hyper-activation of protein degradative pathways and altered mitochondrial function that could both result from impaired redox homeostasis. This study [...] Read more.
Cachexia is a debilitating syndrome that complicates the management of cancer patients. Muscle wasting, one of the main features of cachexia, is associated with hyper-activation of protein degradative pathways and altered mitochondrial function that could both result from impaired redox homeostasis. This study aimed to investigate the contribution of oxidative stress to cancer-induced cachexia in the presence or in the absence of moderate exercise training. Mice bearing the colon C26 carcinoma, either sedentary or exercised, were used. The former showed muscle wasting and redox imbalance, with the activation of an antioxidant response and with upregulation of markers of proteasome-dependent protein degradation and autophagy. Moderate exercise was able to relieve muscle wasting and prevented the loss of muscle strength; such a pattern was associated with reduced levels of Reactive Oxygen Species (ROS), carbonylated proteins and markers of autophagy and with improved antioxidant capacity. The muscle of sedentary tumor hosts also showed increased levels of molecular markers of mitophagy and reduced mitochondrial mass. Conversely, exercise in the C26 hosts led to increased mitochondrial mass. In conclusion, moderate exercise could be an effective non-pharmacological approach to prevent muscle wasting in cancer patients, decreasing muscle protein catabolism and oxidative stress and preserving mitochondria. Full article
(This article belongs to the Special Issue Cancer Cachexia)
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Graphical abstract

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