Advances in the molecular pharmacology of bone and cancer‐related bone diseases

This article is part of a themed issue on The molecular pharmacology bone and cancer-related diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc Over recent years, our understanding mechanisms that drive disorders has dramatically increased, supported by advances technology facilitate dissection cellular crosstalk underpins disease pathogenesis. translated to clinic, with new treatment modalities emerging, alongside research efforts optimise existing therapies. BJP focussing diseases arose from conference held at St Catherine's College Oxford 2018 entitled “The 8th International Workshop Advances Molecular Pharmacology Therapeutics Bone Other Musculoskeletal Diseases” “Cancer Society Meeting.” contains number in-depth review across spectrum basic science through patient care, all addressing key musculoskeletal research. Osteoporosis one most prevalent society, worldwide impact more than 200 million patients, who suffer reduced mass fractures. Pharmacological approaches target either resorption, formation, or both. These different action result clinical responses. For example, greater response mineral density (BMD) observed patients severe osteoporosis receiving treatments stimulate formation such as parathyroid hormone romosozumab (anti-sclerostin antibody) compared anti-resorptives, bisphosphonates denosumab (anti-RANKL antibody). Bente Langdahl (2021) provides comprehensive overview currently available for discusses unmet medical needs move towards personalised optimised approach achieve maximum benefit. skeletal malignancies, cancer-induced major feature, increasing fracture risk causing pain solid tumour metastases, breast prostate cancer metastases. In haematological malignancy multiple myeloma, osteolytic exacerbated suppression formation. effect, majority present disease, anti-resorptives can be effective prevent further loss but unable repair loss. As such, an improved targeting osteoblast are imperative. elegantly discussed Marino et al. (2021), describing underlying dysregulated current followed detailed discussion potential anabolic agents novel emerging preclinical setting show promise translation clinic. challenge repairing lesions area context have huge effect quality life. One driving known hormone-related protein. protein expressed late-stage cells up-regulate RANKL drives component disease. Interestingly, recently, been found roles including protective early role dormancy. Mechanistic studies identified mechanisms, involving canonical signalling parathyroid-1 receptors, non-canonical, mediated distinct domains. Martin Johnson provide these stages, so expanding traditional way thinking opening up avenues molecule. metastases ultimately fatal, metastatic progression vital develop therapeutic approaches. Non-coding RNAs represent and, while they were first 1990s, their importance biological regulators not recognised until 2000s. There evidence demonstrate non-coding (including long ncRNAs, microRNAs, circular RNAs) remodelling metastasis, Puppo (2021). Furthermore, only targets also biomarkers. ability predict those greatest fatal challenging prognostic incredibly exciting. Primary tumours, osteosarcoma, chondrosarcoma, Ewings sarcoma, rare, high morbidity mortality rate, largely consisting surgical resection chemotherapy. emergence anti-cancer immunotherapy revolutionised many cancers, immunotherapies primary tumours. Heymann discuss immune system tumours evidence. They highlight challenges remain, low immunogenicity paediatric providing rationale features pain, areas address. Bisphosphonates well anti-resorptive agents, widely used there both animal models efficacy. However, exploit remain unclear. Thomas Tzschentke describes anti-nociceptive analgesic effects bisphosphonates, action. Aligned this, Sliepen investigate nociceptin/orphanin FQ receptor agonists, demonstrating pain. use decades evident throughout editorial, studied classes drugs It exciting see being explored areas, improving efficacy power stems least bone-homing ability. contrast, micro-environment therapies, resulting drug toxicities limited efficacies. Combining offers alleviate challenges, exploiting unique properties bisphosphonates. Such design strategies described Sun raising revolutionise Notably, it always case community maximises discoveries, rapid ideas pharmacological diseases, facilitated collaborative meetings cross-cutting disciplines, where shared discussed. future looks promising, authors declare no conflicts interest.