Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials

Abstract

Background: Elucidation of mechanisms regulating bone metastasis has progressed significantly in recent years and this has translated to many new therapeutic options for patients with bone metastatic cancers. However, the rapid rate of progress in both the basic science literature and therapies undergoing clinical trials makes staying abreast with current developments challenging. This review seeks to provide an update on the current state of the science in bone metastasis research and give a snap shot of therapies in clinical trials for bone metastatic cancer.

Main body: Bone metastasis represents a difficult to treat clinical scenario due to pain, increased fracture risk, decreased quality of life and diminished overall survival outcomes. Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. This osteotropism was first described by Stephen Paget nearly 100 years ago as the 'seed and soil' hypothesis. Once cancer cells arrive at the bone they encounter a variety of cells native to the bone microenvironment which contribute to the establishment of bone metastatic lesions. In the first part of this review, the 'seed and soil' hypothesis is revisited while emphasizing recent developments in understanding the impact of native bone microenvironment cells on the metastatic process. Next, approved therapies for treating bone metastasis at the systemic level as well as those that target the bone microenvironment are discussed and current National Comprehensive Cancer Network (NCCN) guidelines relating to treatment of bone metastases are summarized. Finally, all open interventional clinical trials for therapies relating to treatment of bone metastasis have been complied and categorized.

Conclusion: Understanding the recent advancements in bone metastasis research is important for continued development of novel bone targeted therapies. The plethora of ongoing clinical trials will hopefully translate into improved treatments options for patients suffering from bone metastatic cancers.

Keywords: Bone metastasis; Clinical trials; Therapies.

Fig. 1

Depiction of the seed and soil hypothesis. The most commonly bone metastatic cancers are thyroid, lung, breast, renal, prostate, and multiple myeloma. The bone microenvironment can be viewed as the soil and contains multiple entities that impact cancer cell survival and establishment of bone lesions. The metastatic process involves: (A) Primary tumor, (B) Angiogenesis, (C) Local invasion and intravasation, (D) Dissemination via circulation, (E) Extravasation, and (F) Colonization of a metastatic site (bone). Components of the bone microenvironment include: endothelial cells, osteocytes, stromal cells, adipose cells, osteoclasts, osteoblasts, T cells, B cells, and the chemical structure of the bone