Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials

Advani, Shailesh; Advani, Pragati G.; VonVille, Helena M.; Jafri, Syed Hasan Raza

doi:10.1186/s12885-018-5080-4

Cited by 96 publications

(92 citation statements)

References 51 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In particular, the identification of several endogenous factors functioning as mediators of CC and the uncovering of their relative mechanisms of action has led to the achievement of important frontiers in this field of oncology. This has allowed the development of potential effective pharmacological agents for the clinical management of this metabolic syndrome (31). Intriguingly, we now know that several of these effectors share the same or similar metabolic effects, and that most often they exhibit synergic effects when administered together.…”

Section: Mediators Of Cc: What Have We Learned From In Vitro and In Vmentioning

confidence: 99%

Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options

2020

View full text Add to dashboard Cite

Cancer cachexia (CC) is a multifactorial syndrome characterized by systemic inflammation, uncontrolled weight loss and dramatic metabolic alterations. This includes myofibrillar protein breakdown, increased lipolysis, insulin resistance, elevated energy expediture, and reduced food intake, hence impairing the patient's response to anti-cancer therapies and quality of life. While a decade ago the syndrome was considered incurable, over the most recent years much efforts have been put into the study of such disease, leading to the development of potential therapeutic strategies. Several important improvements have been reached in the management of CC from both the diagnostic-prognostic and the pharmacological viewpoint. However, given the heterogeneity of the disease, it is impossible to rely only on single variables to properly treat patients presenting this metabolic syndrome. Moreover, the cachexia symptoms are strictly dependent on the type of tumor, stage and the specific patient's response to cancer therapy. Thus, the attempt to translate experimentally effective therapies into the clinical practice results in a great challenge. For this reason, it is of crucial importance to further improve our understanding on the interplay of molecular mechanisms implicated in the onset and progression of CC, giving the opportunity to develop new effective, safe pharmacological treatments. In this review we outline the recent knowledge regarding cachexia mediators and pathways involved in skeletal muscle (SM) and adipose tissue (AT) loss, mainly from the experimental cachexia standpoint, then retracing the unimodal treatment options that have been developed to the present day.

show abstract

Section: Mediators Of Cc: What Have We Learned From In Vitro and In Vmentioning

confidence: 99%

Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options

2020

View full text Add to dashboard Cite

show abstract

“…Studies over the past few decades have identified several mediators of cancer cachexia; however, none of the drugs designed to target these preclinical candidates showed efficacy in clinical trials for the treatment of cancer-associated cachexia in many cancer types, including PDAC [20]. To address the challenges associated with identifying and targeting the mediators of cancer cachexia, our laboratory recently demonstrated that the metal ion transporter Slc39a14 (Zip14) is upregulated in cachectic muscles in the context of metastatic colon, lung, and breast cancers.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia

Shakri

Zhong

et al. 2019

Cancers

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type in which the mortality rate approaches the incidence rate. More than 85% of PDAC patients experience a profound loss of muscle mass and function, known as cachexia. PDAC patients with this condition suffer from decreased tolerance to anti-cancer therapies and often succumb to premature death due to respiratory and cardiac muscle wasting. Yet, there are no approved therapies available to alleviate cachexia. We previously found that upregulation of the metal ion transporter, Zip14, and altered zinc homeostasis are critical mediators of cachexia in metastatic colon, lung, and breast cancer models. Here, we show that a similar mechanism is likely driving the development of cachexia in PDAC. In two independent experimental metastasis models generated from the murine PDAC cell lines, Pan02 and FC1242, we observed aberrant Zip14 expression and increased zinc ion levels in cachectic muscles. Moreover, in advanced PDAC patients, high levels of ZIP14 in muscles correlated with the presence of cachexia. These studies underscore the importance of altered ZIP14 function in PDAC-associated cachexia development and highlight a potential therapeutic opportunity for improving the quality of life and prolonging survival in PDAC patients.

show abstract

“…In addition, other agents have already reached clinical trials, such as myostatin inhibitors [120], the appetite stimulant megestrol acetate [121], testosterone [122], antimyostatin antibody [123], and monoclonal antibody (MABp1) [124], showing the influence of these drugs in different aspects of the spectrum of cancer cachexia. Recently, a combination of drugs to treat patients with cancer cachexia has been tested [125]. On the other hand, some compounds, including thalidomide, produced side effects that may outweigh their potential benefits [126].…”

Section: Treatment Perspectivementioning

confidence: 99%

Cancer Cachexia and Related Metabolic Dysfunction

Fonseca

Farkaš

Dora

et al. 2020

IJMS

View full text Add to dashboard Cite

Cancer cachexia is a complex multifactorial syndrome marked by a continuous depletion of skeletal muscle mass associated, in some cases, with a reduction in fat mass. It is irreversible by nutritional support alone and affects up to 74% of patients with cancer—dependent on the underlying type of cancer—and is associated with physical function impairment, reduced response to cancer-related therapy, and higher mortality. Organs, like muscle, adipose tissue, and liver, play an important role in the progression of cancer cachexia by exacerbating the pro- and anti-inflammatory response initially activated by the tumor and the immune system of the host. Moreover, this metabolic dysfunction is produced by alterations in glucose, lipids, and protein metabolism that, when maintained chronically, may lead to the loss of skeletal muscle and adipose tissue. Although a couple of drugs have yielded positive results in increasing lean body mass with limited impact on physical function, a single therapy has not lead to effective treatment of this condition. Therefore, a multimodal intervention, including pharmacological agents, nutritional support, and physical exercise, may be a reasonable approach for future studies to better understand and prevent the wasting of body compartments in patients with cancer cachexia.

show abstract

Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials

Cited by 96 publications

References 51 publications

Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options

Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options

Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia

Cancer Cachexia and Related Metabolic Dysfunction

Contact Info

Product

Resources

About