Review ArticleAnorexia–cachexia syndrome in pancreatic cancer: Recent advances and new pharmacological approach
Introduction
Pancreatic ductal adenocarcinoma (PDA) is currently one of the most aggressive gastrointestinal carcinomas accounting for a 5-year survival rate of less than 5% and a death-to-incidence ratio of 0.99 [1].
Despite important treatment progress, the survival rate of patients with PDA has not significantly improved over the last few decades [2]. Close to 90% of PDA have advanced disease at presentation; as a consequence, palliative care is the only treatment option for most of these patients. On the other hand, even when the neoplasm is suitable for resection, surgery offers a five-year survival rate of about 25% [3]. Almost all patients with PDA develop metastases and die from the debilitating metabolic effects of their unrestrained growth. The median survival of patients with locally advanced and metastatic disease is 6–9 months and 3–6 months, respectively [4], [5]. One reason contributing to this high mortality is cancer cachexia, defined as an unintended weight loss of more than 10% in 6 months, which is present in more than 80% of PDA [6], [7], with progressive body fat and muscle tissue wasting with associated worsening of their clinical status, lower quality of life and a high mortality rate.
Over the last few years, important new developments regarding the pathogenesis of pancreatic cancer cachexia have been achieved in order to identify palliative measures in this patient population that could also be cost effective [8]. Knowledge of the mechanisms of cancer anorexia–cachexia syndrome is of great importance to lead to effective therapeutic interventions for several aspects of the syndrome. Nevertheless, cachexia remains a poorly understood process whose mechanisms have received only limited attention from cancer researchers [9]. More clinical research is needed to clarify this important subject [10].
Section snippets
Definition and pathogenesis of anorexia–cachexia in pancreatic cancer
Many patients with advanced cancer undergo a wasting syndrome characterized by anorexia, loss of weight, asthenia, and a poor prognosis, referred to as the “cancer anorexia–cachexia syndrome” (CACS) [11].
In cancer patients, anorexia and cachexia can co-exist; while anorexia is defined as the loss of the desire to eat, which frequently leads to reduced food intake, cachexia is characterized by profound loss (up to 80%) of both adipose tissue and skeletal muscle mass that eventually leads to
Conclusions
Considering the complex clinical picture and the multifactorial pathogenesis of CACS, one single therapy may not be completely successful and its management should address the different causes underlying this clinical event. Many drugs including appetite stimulants, thalidomide, cytokine inhibitors, steroids, nonsteroidal anti-inflammatory drugs, branched-chain amino acids, eicosapentaenoic acid, and antiserotoninergic drugs have been proposed and validated in clinical trials, while others are
Conflict of interests
The authors declare no conflicts of interest.
Financial disclosure
The authors have no financing to disclose.
References (64)
- et al.
Palliative therapy for pancreatic/biliary cancer
Surg Oncol Clin N Am
(2004) - et al.
Palliative surgical management of patients with unresectable pancreatic adenocarcinoma: trends and lessons learned from a large, single institution experience
J Gastrointest Surg
(2011) - et al.
Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival
Cell
(2010) - et al.
Muscle wasting in cancer
Int J Biochem Cell Biol
(2013) - et al.
Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis
Am J Clin Nutr
(2006) - et al.
Understanding and managing cancer cachexia
J Am Coll Surg
(2003) - et al.
Cachexia: a new definition
Clin Nutr
(2008) Dietary and pharmacological management of severe catabolic conditions
Am J Med Sci
(2011)- et al.
Supportive care for patients with pancreatic adenocarcinoma: symptom control and nutrition
Hematol Oncol Clin North Am
(2002) - et al.
Mechanism-based therapeutic approaches to cachexia
Vitam Horm
(2013)
Systematic review of megestrol acetate in the treatment of anorexia–cachexia syndrome
J Pain Symptom Manage
Update on melanocortin interventions for cachexia: progress toward clinical application
Nutrition
Therapeutic action of ghrelin in a mouse model of colitis
Gastroenterology
Exogenous ghrelin modulates release of pro-inflammatory and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways
Surgery
Real-imaging cDNA-AFLP transcript profiling of pancreatic cancer patients: Egr-1 as a potential key regulator of muscle cachexia
BMC Cancer
Chemoprevention strategies for pancreatic cancer
Nat Rev Gatroenteral Hepatol
Surgical options in the management of pancreatic cancer
Minerva Chir
Pancreatic cancer related cachexia: influence on metabolism and correlation to weight loss and pulmonary function
BMC Cancer
Prognosis of advanced pancreatic cancer patients with reference to calorie intake
Nutr Cancer
Supportive and Palliative care of Pancreatic cancer
JOP
Anorexia–Cachexia Syndrome in pancreatic cancer: recent development in research and management
JOP
Cancer anorexia–cachexia syndrome: current issues in research and management
CA Cancer J Clin
Cachexia in cancer patients
Nat Rev Cancer
The cancer anorexia–cachexia syndrome
J Clin Oncol
Changes in dietary intake, body weight, nutritional status, and metabolic rate in a pancreatic cancer patient
Clin Nutr Res
Mechanism of cancer cachexia
Physiol Rev
Cachexia and oxidative stress in cancer: an innovative therapeutic management
Curr Pharm Des
Cancer cachexia: mechanisms and clinical implications
Gastroenterol Res Pract
Review article: anorexia and cachexia in gastrointestinal cancer
Aliment Pharmacol Ther
Cancer anorexia–cachexia syndrome: cytokines and neuropeptides
Curr Opin Clin Nutr Metab Care
Cancer anorexia–cachexia syndrome: are neuropeptides the key?
Cancer Res
Role of β-3 adrenergic receptors in the action of tumour lipid mobilizing factor
Br J Cancer
Cited by (34)
Multimodal survival prediction in advanced pancreatic cancer using machine learning
2022, ESMO OpenCitation Excerpt :It could show its potential in survival risk prediction as part of the mGPS.6 More than 80% of PDAC patients are affected by cancer cachexia, which leads to hypoalbuminemia.39 In our study, we have chosen total serum protein level instead of albumin because of the higher availability in our dataset and could show that it was an independent predictor of survival risk.
How can we better predict the prognosis of patients with pancreatic cancer undergoing surgery using an immune-nutritional scoring system?
2022, Surgery (United States)Citation Excerpt :Cancer cachexia is defined as a multifactor syndrome characterized by a sustained loss of skeletal muscle mass.24 Patients with pancreatic cancer have the highest incidence of cancer cachexia and can experience severe cachexia-related symptoms.25–27 Recent studies have demonstrated that complex tumor–host interactions are involved in the development of cancer cachexia in patients with pancreatic cancer.25,28,29
Modeling pancreatic cancer in mice for experimental therapeutics
2021, Biochimica et Biophysica Acta - Reviews on CancerClinical nutrition in patients with cancer
2020, Present Knowledge in Nutrition: Clinical and Applied Topics in NutritionDisease-free survival following resection in non-ductal periampullary cancers: A retrospective multicenter analysis
2017, International Journal of Surgery