Cancer-Associated Fibroblasts as Players in Cancer Development and Progression and Their Role in Targeted Radionuclide Imaging and Therapy

SIMPLE SUMMARY: The tumour microenvironment contains a unique population of cells, of complex origin and diverse functionality, known as Cancer associated fibroblasts (CAFs). In recent years there has been a growing interest in targeting CAFs to aid cancer diagnosis and therapy. Amongst the approaches utilized so far, targeting Fibroblast activation protein (FAP) has shown a lot of promise. In this review, we will focus on our current knowledge of the biology of CAFs as well as theranostic applications that will enhance cancer diagnosis and therapy in cancers carrying a distinct CAF signature. ABSTRACT: Cancer Associated Fibroblasts (CAFs) form a major component of the tumour microenvironment, they have a complex origin and execute diverse functions in tumour development and progression. As such, CAFs constitute an attractive target for novel therapeutic interventions that will aid both diagnosis and treatment of various cancers. There are, however, a few limitations in reaching successful translation of CAF targeted interventions from bench to bedside. Several approaches targeting CAFs have been investigated so far and a few CAF-targeting tracers have successfully been developed and applied. This includes tracers targeting Fibroblast Activation Protein (FAP) on CAFs. A number of FAP-targeting tracers have shown great promise in the clinic. In this review, we summarize our current knowledge of the functional heterogeneity and biology of CAFs in cancer. Moreover, we highlight the latest developments towards theranostic applications that will help tumour characterization, radioligand therapy and staging in cancers with a distinct CAF population.