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      Fibroblast activation protein-based theranostics in cancer research: A state-of-the-art review

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          Abstract

          In recent years, quinoline-based fibroblast activation protein (FAP) inhibitors (FAPI) have shown promising results in the diagnosis of cancer and several other diseases, making them the hotspot of much productive research. This review summarizes the literature for the state-of-the-art FAPI-PET imaging for cancer diagnosis compared with fluorodeoxyglucose (FDG)-PET. We also summarize the use of FAPI-PET for therapeutic regimen improvement and fibroblast activation protein (FAP)-targeted molecule modification strategies, as well as preliminary clinical studies regarding FAP-targeted radionuclide therapy. Our qualitative summary of the literature to date can inform future research directions, medical guidelines, and optimal clinical decision-making.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Microenvironmental regulation of tumor progression and metastasis.

            Daniela Quail, Johanna A. Joyce (2013)
            Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
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              The biology and function of fibroblasts in cancer.

              Raghu Kalluri (2016)
              Among all cells, fibroblasts could be considered the cockroaches of the human body. They survive severe stress that is usually lethal to all other cells, and they are the only normal cell type that can be live-cultured from post-mortem and decaying tissue. Their resilient adaptation may reside in their intrinsic survival programmes and cellular plasticity. Cancer is associated with fibroblasts at all stages of disease progression, including metastasis, and they are a considerable component of the general host response to tissue damage caused by cancer cells. Cancer-associated fibroblasts (CAFs) become synthetic machines that produce many different tumour components. CAFs have a role in creating extracellular matrix (ECM) structure and metabolic and immune reprogramming of the tumour microenvironment with an impact on adaptive resistance to chemotherapy. The pleiotropic actions of CAFs on tumour cells are probably reflective of them being a heterogeneous and plastic population with context-dependent influence on cancer.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Theranostics
                Journal ID (iso-abbrev): Theranostics
                Journal ID (publisher-id): thno
                Title: Theranostics
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1838-7640
                Publication date Collection: 2022
                Publication date (Electronic): 9 January 2022
                Volume: 12
                Issue: 4
                Pages: 1557-1569
                Affiliations
                [1 ]Department of Nuclear Medicine and Minnan PET Center, The First Affiliated Hospital of Xiamen University, Xiamen, China
                [2 ]Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China
                [3 ]Department of Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China
                Author notes
                ✉ Corresponding authors: Long Sun: 13178352662@ 123456163.com . Qin Lin: linqin05@ 123456163.com . Haojun Chen: leochen0821@ 123456foxmail.com ; ORCID ID: 0000-0002-9101-8884.

                # Contributed equally to this work

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                Publisher ID: thnov12p1557
                DOI: 10.7150/thno.69475
                PMC ID: 8825585
                PubMed ID: 35198057
                SO-VID: b2db25ae-f330-40ad-baaa-f0f26684433f
                Copyright © © The author(s)
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                Date received : 26 November 2021
                Date accepted : 29 December 2021
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular medicine
                Keywords: cancer-associated fibroblasts (caf),fibroblast activation protein (fap),targeted radionuclide therapy,pet/ct,cancer management
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: cancer-associated fibroblasts (caf), fibroblast activation protein (fap), targeted radionuclide therapy, pet/ct, cancer management

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