Targeting cancer-induced skeletal damage: a holistic approach to understanding pathophysiology, mechanisms, and management solutions

Abstract

Cancer's insidious reach extends far beyond its initial site, particularly manifesting in the skeleton, where it precipitates a spectrum of pathological conditions ranging from bone metastases and cachexia to primary bone cancers. This review highlights the critical impact of cancer on skeletal health, including the development of bone metastases, cachexia, and primary bone cancers, underscoring the importance of understanding the complex interaction between cancer and the bones. It emphasizes the global burden of cancer and its skeletal complications, which severely affect quality of life. The article reviews the prevalence of bone metastases in various cancers, such as breast, prostate, lung, renal cancers, and multiple myeloma, and stresses the need for targeted treatments. It also discusses the mechanisms behind tumor spread to bones and the systemic effects of cancer, including reduced bone mineral density and increased fracture risk, even without direct bone invasion. The challenges posed by primary bone cancers, which are rarer but highly aggressive, are also examined, highlighting the role of genetics and molecular research in treatment development. The review calls for a multidisciplinary approach to manage the severe symptoms of cancer-induced bone damage and explores the potential of personalized medicine to improve treatment outcomes. It concludes by advocating for continued research and collaboration to develop more precise and personalized therapies for cancer-related bone issues, aiming to improve the lives of those affected.

Keywords: Bone neoplasms; bone density; cachexia; neoplasm metastasis; osteoporosis; therapeutics.

Figure 1

Cancer-induced bone damage: epidemiology, pathophysiology, clinical manifestations, and diagnosis. Created by Figdraw.com (https://www.figdraw.com).

Figure 2

Mechanisms and signaling pathways of cancer-induced skeletal damage. BMPs, Bone Morphogenetic Proteins; IL-1β, Interleukin-1 beta; IGF, Insulin-like Growth Factors; OPG, osteoprotegerin; PTHrP, Parathyroid Hormone-related Protein; NF-κB, Nuclear Factor kappa-light-chain-enhancer of activated B cells; RANKL, Receptor Activator for Nuclear Factor κB Ligand; RANK, Receptor Activator for Nuclear Factor Κb; TNF-α, Tumor Necrosis Factor-alpha; TGF-β, Transforming Growth Factor-beta. Created by Figdraw.com (https://www.figdraw.com).