Ghrelin as a Promising Therapeutic Option for Cancer Cachexia

Khatib, Mahalaqua Nazli; Gaidhane, Abhay; Gaidhane, Shilpa; Quazi, Zahiruddin Syed

doi:10.1159/000492559

Cited by 45 publications

(29 citation statements)

References 165 publications

(242 reference statements)

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“…Appetite stimulants yield marginal results, and most pharmacologic approaches to cancer cachexia do not yield improvements in lean body mass or physical function. [24][25][26] Similarly, fatigue management requires multimodal intervention, and many patients do not have access to evidence-based approaches because of cost and limited insurance coverage. 27,28 Regarding sleep difficulties, although sometimes managed in the short term with medications, they are best addressed using behavioral interventions, such as cognitive behavioral therapy.…”

Section: Discussionmentioning

confidence: 99%

Symptom Burden, Perceived Control, and Quality of Life Among Patients Living With Multiple Myeloma

Zaleta

Miller

Olson

et al. 2020

Journal of the National Comprehensive Cancer Network

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Background: New therapies for multiple myeloma (MM) have improved survival rates but often expose patients to heightened toxicities and prolonged treatment, leading to increasing complications and side effects. We evaluated the association between symptom burden, perceived control over illness, and quality of life (QoL) among a national sample of patients with MM. Methods: For this observational, cross-sectional study, we used data from the Cancer Experience Registry research initiative to examine symptom- and functioning-related concerns among 289 patients with MM across the illness trajectory. We applied hierarchical multiple linear regression analyses to explore associations between symptom burden and perceived control over illness with QoL indicators: depression, anxiety, and social satisfaction. Results: In our sample, 73% of participants with MM reported currently receiving treatment; 39% experienced relapse; 56% received 1 to 2 autologous transplants, 10% received ≥3 autologous transplants, and 4% received allogeneic and autologous transplants; 30% had not received a stem cell transplant. Average time since diagnosis was 4.4 years. The most highly endorsed concerns included eating and nutrition (61%), physical activity (59%), moving around (56%), fatigue (55%), pain (52%), and sleep (46%). Only 27% believed they had control over their disease, whereas 48% perceived having control over the physical side effects of MM. Approximately one-third of the variance in anxiety and depression and nearly two-thirds of variance in social satisfaction were explained by sociodemographic, clinical, and symptom burden variables. Perceived control over illness significantly predicted depression and anxiety, but not social satisfaction. Our results highlight substantial concern among patients with MM about physical symptoms and function. Additionally, greater symptom burden significantly accounted for poorer QoL, and lower perceived control over illness was linked to depression and anxiety. Conclusions: Patients with MM and survivors experience substantive long-term QoL issues. Together, these findings point to the critical need for comprehensive symptom management, integrated palliative care, and enhancement of social and emotional support for individuals with MM.

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Section: Discussionmentioning

confidence: 99%

Symptom Burden, Perceived Control, and Quality of Life Among Patients Living With Multiple Myeloma

Zaleta

Miller

Olson

et al. 2020

Journal of the National Comprehensive Cancer Network

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“…Due to his orexigenic properties, ghrelin has been evaluated as palliative remedy in CC. Ghrelin is mainly produced and secreted by the stomach and, to a lesser extent, by other organs such as pancreas, lung, liver, muscle, and AT (201). Ghrelin mediates multiple pathways involved in the regulation of body weight, body composition, energy storage and appetite, and regulates energy expenditure (202).…”

Section: Metabolism and Appetite Modulatorsmentioning

confidence: 99%

“…In fact, cachectic murine models and cancer patients with cachexia both usually presented hyper-ghrelinemia, though paradoxically showing loss of appetite. This is probably due to grelin's short half-life, which is nearly 30 min (201,203). In order to solve this issue, more stable ghrelin analogs have been developed as potential therapeutic agents.…”

Section: Metabolism and Appetite Modulatorsmentioning

confidence: 99%

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

2020

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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.

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“…We do know, however, that drugs that increase neurogenesis in the hippocampus can enhance resilience in GHSR KO mice . Future research using ghrelin agonists such as anamorelin, a drug that can cross the blood‐brain barrier and one that is also used for the treatment of cachexia, are needed to determine their potential neuroprotective and neurogenic action.…”

Section: Ghrelin Stress and The Hippocampusmentioning

confidence: 99%

Stress and obesity: The ghrelin connection

Abizaid

2019

J Neuroendocrinology

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Ghrelin is a hormone associated with feeding and energy balance. Not surprisingly, this hormone is secreted in response to acute stressors and it is chronically elevated after exposure to chronic stress in tandem with a number of metabolic changes aimed at attaining homeostatic balance. In the present review, we propose that ghrelin plays a key role in these stress‐induced homeostatic processes. Ghrelin targets the hypothalamus and brain stem nuclei that are part of the sympathetic nervous system to increase appetite and energy expenditure and promote the use of carbohydrates as a source of fuel at the same time as sparing fat. Ghrelin also targets mesolimbic brain regions such as the ventral segmental area and the hippocampus to modulate reward processes, to protect against damage associated with chronic stress, as well as to potentially increase resilience to stress. In all, these data support the notion that ghrelin, similar to corticosterone, is a critical metabolic hormone that is essential for the stress response.

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Ghrelin as a Promising Therapeutic Option for Cancer Cachexia

Cited by 45 publications

References 165 publications

Symptom Burden, Perceived Control, and Quality of Life Among Patients Living With Multiple Myeloma

Symptom Burden, Perceived Control, and Quality of Life Among Patients Living With Multiple Myeloma

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

Stress and obesity: The ghrelin connection

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