Abstract
Simple SummaryThe 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.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.
Highlights
Cancer remains the second leading cause of death in the world [1], despite major improvements in diagnosis and therapy
Necessary to evaluate the importance of Cancer Associated Fibroblasts (CAFs) biology and its various functions in cancer to identify specific subsets of the CAF populations that could constitute a springboard for more precise treatments
The majority of efforts so far were only focused on targeting the cancer cells and even though highly abundant, CAFs have long been ignored in these efforts
Summary
Cancer remains the second leading cause of death in the world [1], despite major improvements in diagnosis and therapy This is partly because most of the developed therapeutics are targeting tumour cells ignoring the surrounding tumour microenvironment (TME) [2]. A subpopulation of fibroblasts called cancer associated fibroblasts (CAFs) These cells often constitute a major component in the TME, creating the “ground” in which the tumour cells can grow [7]. Others suggest that a distinct CAF subpopulation, known as myofibroblasts (myCAFs), can have a more tumour-restraining role [8] It is necessary to evaluate the importance of CAF biology and its various functions in cancer to identify specific subsets of the CAF populations that could constitute a springboard for more precise treatments. Even though extensively studied in vitro, the CAF population remains largely uncharacterized in regards to its origin, biology, and subtypes [11], presenting phenotypic heterogeneity and functional diversity [12]
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