Purpose of Review Majority of patients with solid and hematologic cancers associated with osteolytic bone disease suffer from severe uncontrollable bone pain. Treatment of bone pain is an important goal in the management of these cancer patients. However, our understanding of the mechanism underlying cancer-associated bone pain (CABP) is limited and current treatments for CABP are ineffective and unsatisfactory. In this review, the pathophysiology of CABP will be discussed with a special focus on cancer-created acidic bone microenvironment as a potential therapeutic target. Recent Findings Recent accumulating findings that sensory nerves (SNs) densely innervate bone suggest that CABP can be induced as a consequence of SN activation by the pathologic changes in bone microenvironment. Cancer cells proliferating in bone secrete protons and lactate resulting from the Warburg effect, creating acidic bone microenvironment. In parallel, cancer in bone increases and activates osteoclasts, which release protons to degrade bone minerals, also making bone microenvironment acidic. The acidic bone microenvironment sensitizes and excites bone-innervating SNs to evoke CABP via upregulation and activation of the acid-sensing nociceptors such as ASIC3 and TRPV1 expressed on SNs. Blockade of the creation of the acidic bone microenvironment and/or interruption of the activation of these nociceptors decrease
Current Molecular Biology Reports – Springer Journals
Published: Mar 22, 2018
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