Cachexia, a severe wasting syndrome, affects up to 90% of patients with cancer and causes significant morbidity and mortality worldwide. Patients with cachexia suffer from weight loss, anorexia, sarcopenia, and behavioural changes that eventually lead to death. Given its incidence and prevalence, its negative impact on prognosis and quality of life, and the consequent poor tolerance/response to treatment, cachexia is a major global public health burden. In the first chapter of my thesis, I analyse the usage of ketogenic diets (KD) containing high levels of fats as adjuvant therapies in end-stages of cancer that are associated with cachexia. Metabolism of fats through non-enzymatic lipid peroxidation is a recognized source of highly reactive and mutagenic molecules: lipid peroxidation products (LPPs). The biosynthetic pathway of corticosterone, the main regulator of metabolic stress, and the pathway for detoxification of LPPs require NADPH as cofactor but their biochemical interdependency has not been explored. Using two murine models of cancer-associated cachexia, I demonstrate that KD slows down tumour growth but accelerates onset of cachexia in tumour-bearing mice. Reduced tumour size results from accumulation of LPPs, saturation of the GSH detoxifying pathway and ferroptotic death of cancer cells. Moreover, systemic redox state imbalance in KD-fed tumour-bearing mice causes NADPH depletion and primary hypoadrenalism. Dexamethasone treatment delays the onset of cachexia and extends the survival of tumour-bearing mice fed with KD compared to untreated tumour-bearing mice on either KD or standard feeding by improving metabolic homeostasis and utilization of nutritional substrates. Thus, lack of appropriate corticosterone synthesis during cachexia leads to metabolic maladaptation and an inability to use energy sources in mice fed KD. Dexamethasone administration to KD fed mice improves tissue preservation, energy expenditure and survival while preserving reduced tumour growth. In the second chapter I describe neutrophilia as an early event during cancer progression. Transcriptomic and metabolic assessment reveals that neutrophils in tumour-bearing animals utilize aerobic glycolysis, similar to cancer cells. Although pharmacological inhibition of aerobic glycolysis slows down tumour growth in tumour-bearing mice, it precipitates cachexia. This negative effect may be explained by the 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. These findings provide insight into early events during cancer progression to cachexia, with implications for therapy. Lastly, I discuss preliminary data on other potential research avenues in the context of cancer cachexia. These includes understanding the underlying mechanisms behind the behavioural changes observed in cancer that are mediated by the nervous system, the investigation of sexual dimorphism and genetic background with regards to susceptibility to cachexia, disentangling the specific role of interleukin-6 in the metabolic reprogramming associated with cachexia, and the host’s metabolic response to caloric restriction. My results demonstrate that the host response is an important determinant of cancer outcome and argue for the absolute necessity of a combined analysis regarding the effects of candidate cancer treatments on both the tumour and the host.