Examining the metastatic niche: targeting the microenvironment.
Some of the most common cancer types, including breast cancer, prostate cancer, and lung cancer, show a predilection to metastasize to bone. The molecular basis of this preferential growth of cancer cells in the bone microenvironment has been an area of active investigation. Although the precise molecular mechanisms underlying this process remain to be elucidated, it is now increasingly being recognized that the unique characteristics of the bone niche provide homing signals to cancer cells, and create a microenvironment conducive for the cancer cells to colonize. Concomitantly, cancer cells release several regulatory factors that result in abnormal bone destruction and/or formation. This complex bidirectional interplay between tumor cells and bone microenvironment establishes a "vicious cycle" that leads to a selective growth advantage for the cancer cells. The molecular insights gained on the underpinnings of bone metastasis in recent years have also provided us with avenues to devise innovative approaches for therapeutic intervention. The goal of this review is to describe our current understanding of molecular pathophysiology of cancer metastases to bone, as well as its therapeutic implications.
Indiana University, Gatch Clinical Building, Room 459, 541 N Clinical Dr, Indianapolis, IN 46202-5111, USA. tguise@iupui.edu
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D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000145:classification / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D016723:Bone Remodeling / Q000235:genetics / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000145:classification / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D055153:Stem Cell Niche / Q000378:metabolism / Q000473:pathology*; D059016:Tumor Microenvironment / Q000187:drug effects
D000970:Antineoplastic Agents