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

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.

FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?

“…Thereby, CAFs are representing one of the key players in terms of tumor progression and therapeutic response. Adapted with permission from ref [33]…”

“…The transformation to CAFs occurs in concordance with distinct mechanisms including activation, transdifferentiation, mesenchymal transition and recruitment. Adapted with permission from ref [33]…”

First-In-Human Results On The Biodistribution, Pharmacokinetics, And Dosimetry of [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2 in Patients with Various End-stage Cancers

“…The expression of cancer-associated FAP in a broad spectrum of cancers offers an optimal target for various molecular-based FAP inhibitor imaging and therapies [6,7,15] Based on the synthesis of a potent FAP inhibitor UAMC1110 [8, 9], Moon et al, [5] [7]. Though, visual analysis on PTx-[ 177 Lu]Lu-DOTA.SA.SA.FAPi whole-body scan demonstrated a high tumor a nity, early washout of the radiotracer, which was completely eliminated by 48 h p.i.which was the major drawback of the molecule.…”

Fibroblast Activation Protein-α as a Target in the Bench-to-Bedside Diagnosis and Treatment of Tumors: A Narrative Review

“…Therefore, several research groups have explored strategies for treating various tumors by targeting either FAP itself or FAP + CAFs ( Table 2 ). Many tracer drugs that target FAP have shown great clinical promise, not only for diagnosis, but also for treatment ( 131 ).…”