No abstract

Cachexia is a major characteristic of multiple non-malignant diseases, advanced and metastatic cancers and it is highly prevalent in pancreatic cancer, affecting almost 70%–80% of the patients. Cancer cachexia is a multifactorial condition accompanied by compromised appetite and changes in body composition, i.e., loss of fat. It is associated with lower effectiveness of treatment, compromised quality of life, and higher mortality. Understanding the complex pathways underlying the pathophysiology of cancer cachexia, new therapeutic targets will be unraveled. The interplay between tumor and host factors, such as cytokines, holds a central role in cachexia pathophysiology. Cytokines are possibly responsible for anorexia, hypermetabolism, muscle proteolysis, and apoptosis. In particular, cachexia in pancreatic cancer might be the result of the surgical removal of pancreas parts. In recent years, many studies have been carried out to identify an effective treatment algorithm for cachexia. Choosing the most appropriate treatment, the clinical effect and the risk of adverse effects should be taken under consideration. The purpose of this review is to highlight the pathophysiological mechanisms as well as the current ways of cachexia treatment in the pharmaceutical and the nutrition field.

Autophagy as a primary homeostatic and catabolic process is responsible for the degradation and recycling of proteins and cellular components. The mechanism of autophagy has a crucial role in several cellular functions and its dysregulation is associated with tumorigenesis, tumor–stroma interactions, and resistance to cancer therapy. A growing body of evidence suggests that autophagy is also a key regulator of the tumor microenvironment and cellular immune response in different types of cancer, including colorectal cancer (CRC). Furthermore, autophagy is responsible for initiating the immune response especially when it precedes cell death. However, the role of autophagy in CRC and the tumor microenvironment remains controversial. In this review, we identify the role of autophagy in tumor microenvironment regulation and the specific mechanism by which autophagy is implicated in immune responses during CRC tumorigenesis and the context of anticancer therapy.

No abstract

The emergence of cancer immunotherapy has already shown some remarkable results, having changed the treatment strategy in clinical practice for solid tumors. Despite these promising long-term responses, patients seem to lack the ability to respond to immune checkpoint inhibitors, thus demonstrating a primary resistance to immunotherapy. Moreover, a significant number of patients who initially respond to treatment eventually acquire resistance to immunotherapy. Both resistance mechanisms are a result of a complex interaction among different molecules, pathways, and cellular processes. Several resistance mechanisms, such as tumor microenvironment modification, autophagy, genetic and epigenetic alterations, tumor mutational burden, neo-antigens, and modulation of gut microbiota have already been identified, while more continue to be uncovered. In this review, we discuss the latest milestones in the field of immunotherapy, resistance mechanisms against this type of therapy as well as putative therapeutic strategies to overcome resistance in solid tumors.