Project: Acidic microenvironment as atarget for cancerassociated bone pain

Acronym ACIDinCIBP (Reference Number: ELAC2015/T07-0713)
Duration 01/01/2017 - 01/01/2020
Project Topic Cancer associated bone pain (CIBP) is a common event in patients with advanced disease with bone metastases (BM), significantly impairing their quality of life. Treatment options are limited and mainly based on the use of opioids. These are only partially effective, however, and their use is constantly associated with significant patient discomfort. Local acidosis is a wellknown cause of pain due to the stimulation of nociceptors that innervate bone and express acidsensing ion channels, and CIBP elicited by acidity is not targeted by current therapies. In BM, local acidosis occurs as a consequence of acidification of lysosomes of bone resorbing osteoclasts and of tumor cells with high glycolitic activity due to the Warburg effect. The acidic microenvironment of BM can cause pain by promoting a direct acidsensing neuronal stimulation coupled with hyperalgesia that derives from the acidinducedinflammatory reaction at the tumor site. We have preliminary found that local acidosis induces the release of inflammatory mediators by tumorassociated stromal cells via activation of the NFkB pathway, and that vacuolar ATPase blockers, such as omeprazole, strongly and significantly reduce pain in preclinical in vivo models of CIBP.
Network ERANet-LAC
Call 2nd Joint Call on Research and Innovation

Project partner

Number Name Role Country
1 Consejo Nacional de Investigaciones Científicas y Técnicas Partner Argentina
2 Istituto Ortopedico Rizzoli Coordinator Italia
3 Policlinico di Modena Partner Italia
4 Universidade Estadual de Londrina Partner Brasil
5 University Hospital of Muenster Partner Germany