Tumors are complex tissues that consist of stromal cells, such as fibroblasts, immune cells and mesenchymal stem cells, as well as non-cellular components, in addition to neoplastic cells. Increasingly, there is evidence to suggest that these non-neoplastic cell components support cancer initiation, progression and metastasis and that their ablation or reprogramming can inhibit tumor growth. Our understanding of the activities of different parts of the tumor stroma in advancing cancer has been improved by the use of scaffold and matrix-based 3D systems originally developed for regenerative medicine. Additionally, drug delivery systems made from synthetic and natural biomaterials deliver drugs to kill stromal cells or reprogram the microenvironment for tumor inhibition. In this article, we review the impact of 3D tumor models in increasing our understanding of tumorigenesis. We also discuss how different drug delivery systems aid in the reprogramming of tumor stroma for cancer treatment.

Bone metastases are common complications of solid tumors, particularly those of the prostate, breast, and lungs. Bone metastases can lead to painful and devastating skeletal-related events (SREs), such as pathological fractures and nerve compressions. Despite advances in treatment for cancers in general, options for bone metastases remain inadequate and generally palliative. Anticancer drugs (chemotherapy and radiopharmaceuticals) do not achieve therapeutic concentrations in the bone and are associated with dose-limiting side effects to healthy tissues. Nanomedicines, with their tunable characteristics, have the potential to improve drug targeting to bone metastases while decreasing side effects for their effective treatment. In this review, we present the current state of the art for nanomedicines to treat bone metastases. We also discuss new treatment modalities enhanced by nanomedicine and their effects on SREs and disease progression.