Tumors are complex, highly heterogeneous diseases that place an enormous burden on the world's healthcare systems. Updating understanding of tumor initiation and progression is critical and the current breakthrough lies in cancer neuroscience, which focuses on the crosstalk between neural components and tumors. Neuropeptides are a class of highly potent peptides, that perform the physiological functions of neurotransmitters, neuromodulators, and endocrine hormones. Currently, many studies have shown that many cellular components of the tumor microenvironment express neuropeptides and their receptors and that neuropeptides may play an important role in their cellular communication. In addition, neuropeptides and their receptors affect cancer hallmarks such as proliferation, invasion and metastasis, angiogenesis, immune escape, metabolic reprogramming, and others. More importantly, neuropeptides may also affect some tumor comorbidities such as insomnia, depression, anorexia, cancer pain, and others. Targeting neuropeptides in combination with new therapeutic strategies may significantly advance anti-tumor therapy, not only for treating the tumor itself but also for improving the patient's quality of life.

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs, which is mediated by cancer cachexia factors. Cancer cachexia factors, being the general name of inflammatory factors, circulating proteins, metabolites, and microRNA secreted by tumor or host cells, play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia. Cancer cachexia factors are also a potential target for the diagnosis and treatment. The pathogenesis of cachexia is unclear and no clear effective treatment is available. Thus, the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed. From the point of signal communication between organs mediated by cancer cachexia factors, finding a deeper understanding of the pathogenesis, diagnosis, and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment. This review begins with cancer cachexia factors released during the interaction between tumor and host cells, and provides a comprehensive summary of the pathogenesis, diagnosis, and treatment for cancer cachexia, along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors. This summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.