Cancer cachexia: the molecular mechanisms

Abstract

Cancer cachexia is a syndrome characterised by a marked weight loss, anorexia, asthenia and anaemia. In fact, many patients who die with advanced cancer suffer from cancer cachexia. The cachectic state is invariably associated with the presence and growth of the tumour and leads to a malnutrition status due to the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumour and the host leads to an accelerated starvation state which promotes severe metabolic disturbances in the host, including hypermetabolism which leads to an increased energetic inefficiency. Although, the search for the cachectic factor(s) started a long time ago, and although many scientific and economic efforts have been devoted to its discovery, we are still a long way from knowing the whole truth. The main aim of the present review is to summarise and evaluate the different catabolic mediators (both humoural and tumoural) involved in cancer cachexia since they may represent targets for future promising clinical investigations.

Introduction

Perhaps the most common manifestation of advanced malignant disease is the development of cancer cachexia. Indeed, cachexia occurs in the majority of cancer patients before death, and according to Warren it is responsible for the deaths of 22% of cancer patients [1]. The abnormalities associated with cancer cachexia include anorexia, weight loss, muscle loss and atrophy, anaemia and alterations in carbohydrate, lipid and protein metabolism (see [2] for a review). The degree of cachexia is inversely correlated with the survival time of the patient and it always implies a poor prognosis [3]. Perhaps one of the most relevant characteristics of cachexia is that of asthenia (or lack of muscular strength), which reflects the great muscle wasting that takes place in the cachectic cancer patient. Asthenia is also characterized by a general weakness as well as physical and mental fatigue. In addition, lean body mass depletion is one of the main trends of cachexia, and it involves not only skeletal muscle but it also affects cardiac proteins, resulting in important alterations in heart performance.