How does antiangiogenic therapy increase the aggressiveness of tumors?

Antiangiogenic therapy is a promising strategy against solid tumors. This therapy inhibits the formation of new blood vessels in tumors, thereby reducing the oxygen and nutrient supply to prevent further tumor growth and spreading. However, this therapeutic strategy has some limitations, as it is often accompanied by increased tumor aggressiveness in form of invasion and metastasis. Understanding the biological and molecular basis of tumor malignization is a key aspect to predict how and when antiangiogenic therapy is likely to work. And most importantly, to improve its effectiveness and extend patient survival.

Cancer cells do not only form a tumor mass of mutated and uncontrollably dividing cells. In fact, they are part of a complex ecosystem consisting of different cell types that work and communicate together within an extracellular matrix that holds and protects them. This whole set of cells and complex molecules is what we call the tumor microenvironment.

Tumor initiation, progression, and malignization highly depend on the interaction with these microenvironmental components, and one of the main actors in this ecosystem is angiogenesis, the formation of blood vessels. Felix Peix and Oriol Casanovas, group leader of the IDIBELL and ICO Tumor Angiogenesis research group, have just published an article in the journal Seminars in Cancer Biology that reviews everything known about the remodeling of the tumor microenvironment by antiangiogenic therapy and how this could instigate tumor aggressiveness.

The article reviews how antiangiogenics induce hypoxia, mechanical stress, and acidification of the tumor microenvironment, and how all these changes are detected by surface receptors of tumor cells. As a result, tumor cells react to changes in the environment and activate some type of defense mechanism to adapt.

Felix Peix and Oriol Casanovas declare: “Targeting these multiple receptors and sensors of cancer cells might represent an effective treatment that prevents the formation of malignant side effects of antiangiogenic therapy.”

The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).