The landscape of cancer cachexia in advanced non-small cell lung cancer: a narrative review

Abstract

Background and objective: Cancer cachexia presents with weight loss, anorexia, and fatigue and worsens the prognosis and quality of life of cancer patients. We aimed to summarize the current relevant discourse in the literature about cancer cachexia in the setting of non-small cell lung carcinoma and the possible current and future treatments.

Methods: We conduct a narrative review of the literature on the landscape of cancer cachexia in the context of non-small cell lung cancer, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances.

Key content and findings: The need for appropriate intervention for cancer cachexia is increasing as the prognosis of patients with advanced non-small cell lung cancer is improving with advances in treatment. Tumor cells play a role in the pathogenesis of cachexia, where they release factors that elicit the production of inflammatory cytokines by the immune system resulting in decreased appetite, abnormal energy metabolism, and skeletal muscle degeneration. Comorbid chronic lung diseases are associated with pulmonary cachexia and sarcopenia and commonly occur in the context of lung cancer, further contributing to the increased incidence of cachexia in patients with lung cancer. Currently, a ghrelin-like agonist, anamorelin, is approved for the treatment of cancer cachexia and is used in clinical practice in Japan. The role that nutritional and exercise therapies can play as added treatments must be further explored.

Conclusions: Cancer cachexia remains a poorly understood phenomenon, and awareness must be raised through educational activities for health care providers and patient family members. In addition, new therapeutics targeting cancer cachexia, such as GDF-15 antibodies, are in development, and further progress is expected.

Keywords: Cancer cachexia; anamorelin; immune-checkpoint inhibitor; non-small cell lung cancer.

Figure 1

The history of cancer cachexia and anti-non-small cell lung cancer therapy. With the progress of non-small cell lung cancer drug therapy, overcoming cancer cachexia, a poor prognostic factor for advanced cancer, has become the next major challenge. The definitions and diagnostic criteria of “cachexia” and “cancer cachexia” were established in 2006 and 2011, respectively. Research aimed at the development of cancer cachexia treatment methods has progressed, and in 2021, the world’s first ghrelin-like drug with anti-cancer cachexia action, “anamorelin”, was launched in Japan. NSCLC, non-small cell lung cancer.

Figure 2

The role of multiple factors associated with cancer cachexia. (A) The relationship between cancer cachexia and multiple organs. These diverse factors, such as GDF-15, IL-6, ghrelin, and leptin, cause cachexia pathology by acting on systemic organs, such as the skeletal muscle, adipocytes, brain, liver, bone, and pancreas, myocardium, and gastrointestinal tract. (B) Lung cancer, pulmonary disease, and cachexia. It has been speculated that one of the reasons for the high incidence of cachexia in lung cancer is related to its occurrence secondary to chronic lung diseases, such as COPD or IPF, in addition to the rate of disease progression of advanced cancer. GDF-15, growth differentiation factor-15; PTHrP, parathyroid hormone-related peptide; MDSCs, myeloid-derived suppressor cells; IL-6, interleukin-6; COPD, chronic obstructive pulmonary disease; IPF, idiopathic pulmonary fibrosis.