The prevalence of cancer is expected to increase. Thus, the need
for effective anti-cancer therapy is increasing. The progression of aggressive cancer occurs via angiogenesis and metastasis making these processes important targets for the development of anti-cancer drugs. However, recent studies have raised the concern that selective inhibition of angiogenesis results in a switch towards increased tumour growth and cell spreading. Annexin A2 plays a role in the development of a number of different cancers and chemotherapy resistance. Moreover, it is often regarded as a marker for aggressive cancer types, consequently emerging as a promising target for anti-cancer therapy. Annexin A2, a multifunctional protein, is involved in several processes associated with cell migration such as angiogenesis and metastasis. Furthermore, Annexin A2 plays a role in the transport and translation of specific mRNAs, such as its cognate mRNA. Since Annexin A2 is involved in both angiogenesis and metastasis it may provide an ideal target for simultaneous inhibition of both processes. Also, increased plasma levels of Annexin A2 have also been associated with stimulation of the immune system and therefore also related to immune therapy of cancer. Thus, it is of great interest to obtain a compound that may increase the expression of Annexin A2 only temporarily. Prohibitins interact with Annexin A2 and the activities of the multifunctional prohibitins are regulated by flavaglines, which are natural compounds. These compounds relieve the resistance to cancer chemotherapies and display a strong cytotoxicity that is specific to cancer cells. Prof. Désaubry in France is an expert on prohibitins and flavaglines, as well as other prohibitin ligands while Prof. Vedeler in Norway is an expert on Annexin A2 including its mRNA-binding properties.By joining efforts, we aim at modulating the expression and/or activity of Annexin A2 by using the prohibitins and flavaglines.