Regulation of Tumor Progression and Metastasis by Bone Marrow-Derived Microenvironments

Home Biomarkers of the Tumor Microenvironment Chapter Regulation of Tumor Progression and Metastasis by Bone Marrow-Derived Microenvironments Divya Ramchandani, Tyler P. El Rayes, Dingcheng Gao, Nasser K. Altorki, Thomas R. Cox, Janine T. Erler & Vivek Mittal Chapter First Online: 13 July 2022 968 Accesses Abstract Activating mutations in driver oncogenes and loss-of-function mutations in tumor suppressor genes contribute to tumor progression and metastasis. Accordingly, therapies targeting key tumor cell intrinsic signaling pathways are being used in clinical trials, and some have met FDA approval. However, these treatments benefit only a small proportion of patients harboring key driver mutations and acquired resistance to these therapies presents a major impediment to effective treatment. More recently, the contribution of the tumor microenvironment (TME) has been an area of active investigation and has begun to provide critical insights into carcinogenesis. The host stromal cells in the TME co-evolve with tumors and contribute to carcinogenesis in several ways. Among the host cells, bone marrow (BM)-derived cells constitute a significant fraction and directly contribute to proliferation, invasion, intravasation, extravasation, and outgrowth at the metastatic site. While the tumor reprogrammed BM cells constitute attractive targets for anti-cancer therapy, recent studies have also begun to unravel their role as prognostic and predictive molecular markers of the disease. In this chapter, we will focus on recent advances and emerging concepts of the contribution of BM-derived cells in various steps of primary tumor progression and the metastatic cascade (Fig. 14.1) and discuss future directions in the context of novel diagnostic and therapeutic opportunities.