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

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