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Cancer-Associated Cachexia

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 40958

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Dr. Maria Rohm

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Guest Editor

Institute for Diabetes and Cancer, Helmholtz Zentrum München – German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg 85764, Germany
Interests: cachexia; Cancer Metabolism; cancer-related death

Dr. Swarnali Acharyya

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Guest Editor

1. Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, NY 10032, USA
2. Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA
Interests: cancer Cachexia; drug resistance; cancer metastasis; metastatic breast cancer and lung cancer

Dr. Pauline Morigny

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Co-Guest Editor

Institute for Diabetes and Cancer, Helmholtz Zentrum Munich, Ingolstädter Landstraβe 1, 85764 Neuherberg, Germany
Interests: cachexia; Cancer Metabolism; cancer-related death

Special Issue Information

Dear Colleagues

Many types of cancer are associated with cachexia, a multifactorial wasting disease that weakens the body, perturbs quality of life, and minimizes the success of underlying tumor treatment and, ultimately, survival. Body wasting is largely attributed to a loss of skeletal muscle and adipose tissue mass, but cachexia is a multiorgan disease that also affects other tissues including the liver, heart, brain, and gastrointestinal tract as well as the immune system. This occurs as a result of anorexia and metabolic malfunction induced either directly or indirectly by the tumor. It has been estimated that 80% of metastatic cancers exhibit features of cachexia, with muscle mass and/or function loss. The highest incidences of cachexia have been observed in patients with pancreatic, gastrointestinal, and lung cancers.

In addition to pro-inflammatory cytokines (most prominently, TNFα and IL6, which are well-established cachexia-inducing factors), more recent studies have identified novel mediators of cachexia which are secreted either directly by the tumor or mediate wasting through interorgan crosstalk. Among these are members of the TGFβ family (myostatin, activin A), IFNγ, LIF, ZAG, and many more new candidates linked to metabolism. Increased lipolysis in adipose tissue and proteolysis in skeletal muscle account for the majority of the weight loss, but the importance of liver acute-phase response, cardiac atrophy, and metaflammation is becoming increasingly evident.

Despite our growing knowledge of the causes and consequences of cachexia in recent years, we are still lacking efficient treatment strategies to counteract wasting.

Overall, we still need to deepen our understanding of the molecular principles of energy loss in cachexia as well as the factors promoting body wasting in the context of cancer progression and metabolism. Likewise, identifying specific biomarkers which enable us to detect and treat cachexia at an early stage would greatly improve our chances of efficiently treating this disease. This Special Issue “Cancer-Associated Cachexia” is therefore dedicated to highlighting recent advances in understanding and targeting wasting mechanisms in cancer.

Dr. Maria Rohm
Dr. Swarnali Acharyya
Dr. Pauline Morigny
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. Cancers 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 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

Cachexia
Wasting
Energy metabolism
Tumor-secreted factors
Adipose tissue
Skeletal muscle
Novel targets

Published Papers (11 papers)

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23 pages, 2769 KiB

Open AccessArticle

Apelin Resistance Contributes to Muscle Loss during Cancer Cachexia in Mice

by Andrea David Re Cecconi, Mara Barone, Mara Forti, Martina Lunardi, Alfredo Cagnotto, Mario Salmona, Davide Olivari, Lorena Zentilin, Andrea Resovi, Perla Persichitti, Dorina Belotti, Federica Palo, Nobuyuki Takakura, Hiroyasu Kidoya and Rosanna Piccirillo

Cancers 2022, 14(7), 1814; https://doi.org/10.3390/cancers14071814 - 2 Apr 2022

Cited by 3 | Viewed by 3152

Abstract

Cancer cachexia consists of dramatic body weight loss with rapid muscle depletion due to imbalanced protein homeostasis. We found that the mRNA levels of apelin decrease in muscles from cachectic hepatoma-bearing rats and three mouse models of cachexia. Furthermore, apelin expression inversely correlates with MuRF1 in muscle biopsies from cancer patients. To shed light on the possible role of apelin in cachexia in vivo, we generated apelin 13 carrying all the last 13 amino acids of apelin in D isomers, ultimately extending plasma stability. Notably, apelin D-peptides alter cAMP-based signaling in vitro as the L-peptides, supporting receptor binding. In vitro apelin 13 protects myotube diameter from dexamethasone-induced atrophy, restrains rates of degradation of long-lived proteins and MuRF1 expression, but fails to protect mice from atrophy. D-apelin 13 given intraperitoneally for 13 days in colon adenocarcinoma C26-bearing mice does not reduce catabolic pathways in muscles, as it does in vitro. Puzzlingly, the levels of circulating apelin seemingly deriving from cachexia-inducing tumors, increase in murine plasma during cachexia. Muscle electroporation of a plasmid expressing its receptor APJ, unlike apelin, preserves myofiber area from C26-induced atrophy, supporting apelin resistance in vivo. Altogether, we believe that during cachexia apelin resistance occurs, contributing to muscle wasting and nullifying any possible peptide-based treatment. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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21 pages, 3191 KiB

Open AccessArticle

Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia

by Michele Petruzzelli, Miriam Ferrer, Martijn J. Schuijs, Sam O. Kleeman, Nicholas Mourikis, Zoe Hall, David Perera, Shwethaa Raghunathan, Michele Vacca, Edoardo Gaude, Michael J. Lukey, Duncan I. Jodrell, Christian Frezza, Erwin F. Wagner, Ashok R. Venkitaraman, Timotheus Y. F. Halim and Tobias Janowitz

Cancers 2022, 14(4), 963; https://doi.org/10.3390/cancers14040963 - 15 Feb 2022

Cited by 9 | Viewed by 3681

Abstract

An elevated neutrophil–lymphocyte ratio negatively predicts the outcome of patients with cancer and is associated with cachexia, the terminal wasting syndrome. Here, using murine model systems of colorectal and pancreatic cancer we show that neutrophilia in the circulation and multiple organs, accompanied by extramedullary hematopoiesis, is an early event during cancer progression. Transcriptomic and metabolic assessment reveals that neutrophils in tumor-bearing animals utilize aerobic glycolysis, similar to cancer cells. Although pharmacological inhibition of aerobic glycolysis slows down tumor growth in C26 tumor-bearing mice, it precipitates cachexia, thereby shortening the overall survival. This negative effect may be explained by our observation that acute depletion of neutrophils in pre-cachectic mice impairs systemic glucose homeostasis secondary to altered hepatic lipid processing. Thus, changes in neutrophil number, distribution, and metabolism play an adaptive role in host metabolic homeostasis during cancer progression. Our findings provide insight into early events during cancer progression to cachexia, with implications for therapy. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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15 pages, 11337 KiB

Open AccessArticle

Skeletal Muscle Depletion and Major Postoperative Complications in Locally-Advanced Head and Neck Cancer: A Comparison between Ultrasound of Rectus Femoris Muscle and Neck Cross-Sectional Imaging

by Andrea Galli, Michele Colombo, Carmine Prizio, Giulia Carrara, Francesca Lira Luce, Pier Luigi Paesano, Giovanna Della Vecchia, Leone Giordano, Stefano Bondi, Michele Tulli, Davide Di Santo, Aurora Mirabile, Francesco De Cobelli and Mario Bussi

Cancers 2022, 14(2), 347; https://doi.org/10.3390/cancers14020347 - 11 Jan 2022

Cited by 10 | Viewed by 1750

Abstract

Skeletal muscle mass (SMM) depletion has been validated in many surgical fields as independent predictor of complications through cross-sectional imaging. We evaluated SMM depletion in a stage III-IV head and neck cancer cohort, comparing the accuracy of CT/MRI at C3 level with ultrasound (US) of rectus femoris muscle (RF) in terms of prediction of major complications. Patients submitted to surgery were recruited from 2016 to 2021. SMM was estimated on CT/MRI by calculating the sum of the cross-sectional area (CSA) of the sternocleidomastoid and paravertebral muscles at C3 level and its height-indexed value (cervical skeletal muscle index, CSMI) and on US by computing the CSA of RF. Specific thresholds were defined for both US and CT/MRI according to ROC curve in terms of best prediction of 30-day major complications to detect sarcopenic subjects (40–53%). Sixty-five patients completed the study. At univariate analysis, major complications were associated to lower RF CSA, lower CSA at C3 level and lower CSMI, together with previous radiotherapy, higher ASA score and higher modified frailty index (mFI). At multivariate analysis RF CSA (OR 7.07, p = 0.004), CSA at C3 level (OR 6.74, p = 0.005) and CSMI (OR 4.02, p = 0.025) were confirmed as independent predictors in three different models including radiotherapy, ASA score and mFI. This analysis proved the value of SMM depletion as predictor of major complications in a head and neck cancer cohort, either defined on cross-sectional imaging at C3 or on US of RF. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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21 pages, 6849 KiB

Open AccessArticle

Aging Aggravates Cachexia in Tumor-Bearing Mice

by Julia Geppert, Alina A. Walth, Raúl Terrón Expósito, Doris Kaltenecker, Pauline Morigny, Juliano Machado, Maike Becker, Estefania Simoes, Joanna D. C. C. Lima, Carolin Daniel, Mauricio Berriel Diaz, Stephan Herzig, Marilia Seelaender and Maria Rohm

Cancers 2022, 14(1), 90; https://doi.org/10.3390/cancers14010090 - 24 Dec 2021

Cited by 9 | Viewed by 4753

Abstract

Background: Cancer is primarily a disease of high age in humans, yet most mouse studies on cancer cachexia are conducted using young adolescent mice. Given that metabolism and muscle function change with age, we hypothesized that aging may affect cachexia progression in mouse models. Methods: We compare tumor and cachexia development in young and old mice of three different strains (C57BL/6J, C57BL/6N, BALB/c) and with two different tumor cell lines (Lewis Lung Cancer, Colon26). Tumor size, body and organ weights, fiber cross-sectional area, circulating cachexia biomarkers, and molecular markers of muscle atrophy and adipose tissue wasting are shown. We correlate inflammatory markers and body weight dependent on age in patients with cancer. Results: We note fundamental differences between mouse strains. Aging aggravates weight loss in LLC-injected C57BL/6J mice, drives it in C57BL/6N mice, and does not influence weight loss in C26-injected BALB/c mice. Glucose tolerance is unchanged in cachectic young and old mice. The stress marker GDF15 is elevated in cachectic BALB/c mice independent of age and increased in old C57BL/6N and J mice. Inflammatory markers correlate significantly with weight loss only in young mice and patients. Conclusions: Aging affects cachexia development and progression in mice in a strain-dependent manner and influences the inflammatory profile in both mice and patients. Age is an important factor to consider for future cachexia studies. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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17 pages, 3069 KiB

Open AccessArticle

Bile Acid Dysregulation Is Intrinsically Related to Cachexia in Tumor-Bearing Mice

by Morgane M. Thibaut, Justine Gillard, Adeline Dolly, Martin Roumain, Isabelle A. Leclercq, Nathalie M. Delzenne, Giulio G. Muccioli and Laure B. Bindels

Cancers 2021, 13(24), 6389; https://doi.org/10.3390/cancers13246389 - 20 Dec 2021

Cited by 6 | Viewed by 2931

Abstract

Bile acids exert diverse actions on host metabolism and immunity through bile acid-activated receptors, including Takeda G protein-coupled receptor 5 (TGR5). We have recently evidenced an alteration in bile acids in cancer cachexia, an inflammatory and metabolic syndrome contributing to cancer death. This current study aims to further explore the links emerging between bile acids and cancer cachexia. First, we showed that bile flow is reduced in cachectic mice. Next, comparing mice inoculated with cachexia-inducing and with non-cachexia-inducing C26 colon carcinoma cells, we demonstrated that alterations in the bile acid pathways and profile are directly associated with cachexia. Finally, we performed an interventional study using ursodeoxycholic acid (UDCA), a compound commonly used in hepatobiliary disorders, to induce bile acid secretion and decrease inflammation. We found that UDCA does not improve hepatic inflammation and worsens muscle atrophy in cachectic mice. This exacerbation of the cachectic phenotype upon UDCA was accompanied by a decreased TGR5 activity, suggesting that TGR5 agonists, known to reduce inflammation in several pathological conditions, could potentially counteract cachectic features. This work brings to light major evidence sustaining the emerging links between bile acids and cancer cachexia and reinforces the interest in studying bile acid-activated receptors in this context. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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13 pages, 1113 KiB

Open AccessArticle

Activation of the Complement System in Patients with Cancer Cachexia

by Min Deng, Rianne D. W. Vaes, Annemarie A. J. H. M. van Bijnen, Steven W. M. Olde Damink and Sander S. Rensen

Cancers 2021, 13(22), 5767; https://doi.org/10.3390/cancers13225767 - 17 Nov 2021

Cited by 5 | Viewed by 2180

Abstract

Systemic inflammation is thought to underlie many of the metabolic manifestations of cachexia in cancer patients. The complement system is an important component of innate immunity that has been shown to contribute to metabolic inflammation. We hypothesized that systemic inflammation in patients with cancer cachexia was associated with complement activation. Systemic C3a levels were higher in cachectic patients with inflammation (n = 23, C-reactive protein (CRP) ≥ 10 mg/L) as compared to patients without inflammation (n = 26, CRP < 10 mg/L) or without cachexia (n = 13) (medians 102.4 (IQR 89.4–158.0) vs. 81.4 (IQR 47.9–124.0) vs. 61.6 (IQR 46.8–86.8) ng/mL, respectively, p = 0.0186). Accordingly, terminal complement complex (TCC) concentrations gradually increased in these patient groups (medians 2298 (IQR 2022–3058) vs. 1939 (IQR 1725–2311) vs. 1805 (IQR 1552–2569) mAU/mL, respectively, p = 0.0511). C3a and TCC concentrations were strongly correlated (r_s = 0.468, p = 0.0005). Although concentrations of C1q and mannose-binding lectin did not differ between groups, C1q levels were correlated with both C3a and TCC concentrations (r_s = 0.394, p = 0.0042 and r_s = 0.300, p = 0.0188, respectively). In conclusion, systemic inflammation in patients with cancer cachexia is associated with the activation of key effector complement factors. The correlations between C1q and C3a/TCC suggest that the classical complement pathway could play a role in complement activation in patients with pancreatic cancer. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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15 pages, 37173 KiB

Open AccessArticle

MRI-Determined Psoas Muscle Fat Infiltration Correlates with Severity of Weight Loss during Cancer Cachexia

by Lisa Patzelt, Daniela Junker, Jan Syväri, Egon Burian, Mingming Wu, Olga Prokopchuk, Ulrich Nitsche, Marcus R. Makowski, Rickmer F. Braren, Stephan Herzig, Mauricio Berriel Diaz and Dimitrios C. Karampinos

Cancers 2021, 13(17), 4433; https://doi.org/10.3390/cancers13174433 - 2 Sep 2021

Cited by 7 | Viewed by 3148

Abstract

Purpose: To evaluate the suitability of psoas and erector spinae muscle proton density fat fraction (PDFF) and fat volume as biomarkers for monitoring cachexia severity in an oncological cohort, and to evaluate regional variances in muscle parameters over time. Methods: In this prospective study, 58 oncological patients were examined by a 3 T MRI receiving between one and five scans. Muscle volume and PDFF were measured, segmentation masks were divided into proximal, middle and distal muscle section. Results: A regional variation of fat distribution in erector spinae muscle at baseline was found (p < 0.01). During follow-ups significant relative change of muscle parameters was observed. Relative maximum change of erector spinae muscle showed a significant regional variation. Correlation testing with age as a covariate revealed significant correlations for baseline psoas fat volume (r = −0.55, p < 0.01) and baseline psoas PDFF (r = −0.52, p = 0.02) with maximum BMI change during the course of the disease. Conclusion: In erector spinae muscles, a regional variation of fat distribution at baseline and relative maximum change of muscle parameters was observed. Our results indicate that psoas muscle PDFF and fat volume could serve as MRI-determined biomarkers for early risk stratification and disease monitoring regarding progression and severity of weight loss in cancer cachexia. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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14 pages, 1282 KiB

Open AccessArticle

Association between Skeletal Muscle Loss and the Response to Neoadjuvant Chemotherapy for Breast Cancer

by Byung Min Lee, Yeona Cho, Jun Won Kim, Sung Gwe Ahn, Jee Hung Kim, Hei Cheul Jeung, Joon Jeong and Ik Jae Lee

Cancers 2021, 13(8), 1806; https://doi.org/10.3390/cancers13081806 - 9 Apr 2021

Cited by 7 | Viewed by 4328

Abstract

There are no means to predict patient response to neoadjuvant chemotherapy (NAC); the impact of skeletal muscle loss on the response to NAC remains undefined. We investigated the association between response to chemotherapy and skeletal muscle loss in breast cancer patients. Patients diagnosed with invasive breast cancer who were treated with NAC, surgery, and radiotherapy were analyzed. We quantified skeletal muscle loss using pre-NAC and post-NAC computed tomography scans. The response to treatment was determined using the Response Evaluation Criteria in Solid Tumors. We included 246 patients in this study (median follow-up, 28.85 months). The median age was 48 years old (interquartile range 42–54) and 115 patients were less than 48 years old (46.7%). Patients showing a complete or partial response were categorized into the responder group (208 patients); the rest were categorized into the non-responder group (38 patients). The skeletal muscle mass cut-off value was determined using a receiver operating characteristic curve; it showed areas under the curve of 0.732 and 0.885 for the pre-NAC and post-NAC skeletal muscle index (p < 0.001 for both), respectively. Skeletal muscle loss and cancer stage were significantly associated with poor response to NAC in locally advanced breast cancer patients. Accurately measuring muscle loss to guide treatment and delaying muscle loss through various interventions would help enhance the response to NAC and improve clinical outcomes. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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20 pages, 3681 KiB

Open AccessArticle

Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy-Induced Cachexia

by Riccardo Ballarò, Patrizia Lopalco, Valentina Audrito, Marc Beltrà, Fabrizio Pin, Roberto Angelini, Paola Costelli, Angela Corcelli, Andrea Bonetto, Hazel H. Szeto, Thomas M. O’Connell and Fabio Penna

Cancers 2021, 13(4), 850; https://doi.org/10.3390/cancers13040850 - 18 Feb 2021

Cited by 32 | Viewed by 4848

Abstract

Objective: Cachexia is a complex metabolic syndrome frequently occurring in cancer patients and exacerbated by chemotherapy. In skeletal muscle of cancer hosts, reduced oxidative capacity and low intracellular ATP resulting from abnormal mitochondrial function were described. Methods: The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not. Results: Mitochondrial dysfunction in C26-bearing (C26) mice associated with alterations of cardiolipin fatty acid chains. Selectively targeting cardiolipin with SS-31 partially counteracted body wasting and prevented the reduction of glycolytic myofiber area. SS-31 prompted muscle mitochondrial succinate dehydrogenase (SDH) activity and rescued intracellular ATP levels, although it was unable to counteract mitochondrial protein loss. Progressively increased dosing of SS-31 to C26 OXFU mice showed transient (21 days) beneficial effects on body and muscle weight loss before the onset of a refractory end-stage condition (28 days). At day 21, SS-31 prevented mitochondrial loss and abnormal autophagy/mitophagy. Skeletal muscle, liver and plasma metabolomes were analyzed, showing marked energy and protein metabolism alterations in tumor hosts. SS-31 partially modulated skeletal muscle and liver metabolome, likely reflecting an improved systemic energy homeostasis. Conclusions: The results suggest that targeting mitochondrial function may be as important as targeting protein anabolism/catabolism for the prevention of cancer cachexia. With this in mind, prospective multi-modal therapies including SS-31 are warranted. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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10 pages, 899 KiB

Open AccessArticle

Association between Growth Differentiation Factor-15 (GDF-15) Serum Levels, Anorexia and Low Muscle Mass among Cancer Patients

by Alessio Molfino, Maria Ida Amabile, Giovanni Imbimbo, Veronica Rizzo, Federica Pediconi, Carlo Catalano, Alessandra Emiliani, Roberta Belli, Cesarina Ramaccini, Claudia Parisi, Giuseppe Nigri and Maurizio Muscaritoli

Cancers 2021, 13(1), 99; https://doi.org/10.3390/cancers13010099 - 31 Dec 2020

Cited by 25 | Viewed by 2711

Abstract

The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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17 pages, 1838 KiB

Open AccessReview

Neural Mechanisms of Cancer Cachexia

by Brennan Olson, Parham Diba, Tetiana Korzun and Daniel L. Marks

Cancers 2021, 13(16), 3990; https://doi.org/10.3390/cancers13163990 - 7 Aug 2021

Cited by 20 | Viewed by 5706

Abstract

Nearly half of cancer patients suffer from cachexia, a metabolic syndrome characterized by progressive atrophy of fat and lean body mass. This state of excess catabolism decreases quality of life, ability to tolerate treatment and eventual survival, yet no effective therapies exist. Although the central nervous system (CNS) orchestrates several manifestations of cachexia, the precise mechanisms of neural dysfunction during cachexia are still being unveiled. Herein, we summarize the cellular and molecular mechanisms of CNS dysfunction during cancer cachexia with a focus on inflammatory, autonomic and neuroendocrine processes and end with a discussion of recently identified CNS mediators of cachexia, including GDF15, LCN2 and INSL3. Full article

(This article belongs to the Special Issue Cancer-Associated Cachexia)

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