Multifarious Targets and Recent Developments in the Therapeutics for the Management of Bone Cancer Pain

Bone cancer pain (BCP) is a distinct pain state showing characteristics of both neuropathic and inflammatory pain. On average, almost 46% of cancer patients exhibit BCP with numbers flaring up to as high as 76% for terminally ill patients. Patients suffering from BCP experience a compromised quality of life, and the unavailability of effective therapeutics makes this a more devastating condition. In every individual cancer patient, the pain is driven by different mechanisms at different sites. The mechanisms behind the manifestation of BCP are very complex and poorly understood, which creates a substantial barrier to drug development. Nevertheless, some of the key mechanisms involved have been identified and are being explored further to develop targeted molecules. Developing a multitarget approach might be beneficial in this case as the underlying mechanism is not fixed and usually a number of these pathways are simultaneously dysregulated. In this review, we have discussed the role of recently identified novel modulators and mechanisms involved in the development of BCP. They include ion channels and receptors involved in sensing alteration of temperature and acidic microenvironment, immune system activation, sodium channels, endothelins, protease-activated receptors, neurotrophins, motor proteins mediated trafficking of glutamate receptor, and some bone-specific mechanisms. Apart from this, we have also discussed some of the novel approaches under preclinical and clinical development for the treatment of bone cancer pain.