|Table of Contents|

Research progress on the tumor-promoting effects of cancer-associated fibroblasts and their targeted therapy

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 16
Page:
3156-3160
Research Field:
Publishing date:

Info

Title:
Research progress on the tumor-promoting effects of cancer-associated fibroblasts and their targeted therapy
Author(s):
ZENG Ruiqi1HE Weiyang2ZENG Tiebing1CHEN Xiaobin1
1.Department of Urology,the Second People's Hospital of Yibin,Sichuan Yibin 644000,China;2.Department of Urology,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China.
Keywords:
tumor microenvironmentcancer-associated fibroblaststumor targeted therapyimmunotherapy
PACS:
R730.5
DOI:
10.3969/j.issn.1672-4992.2024.16.034
Abstract:
Tumor microenvironment (TME) plays a great role in promoting the occurrence,development and treatment resistance of tumors.Among all the interstitial cells in TME,cancer-associated fibroblasts (CAFs) are the most abundant,which have powerful functions of promoting tumor angiogenesis,interstitial remodeling,drug resistance and immunosuppression.In this article,we focus on the recent advances in targeted therapy of CAFs in terms of their cellular origin,tumor-promoting mechanism and specificity,in order to provide reference for the research of new anti-tumor therapy targeting CAFs.

References:

[1] LUO H,XIA X,HUANG LB,et al.Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment[J].Nat Commun,2022,13(1):6619.
[2] ZHANG H,YUE X,CHEN Z,et al.Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment:new opportunities in cancer immunotherapy and advances in clinical trials[J].Mol Cancer 2023,22(1):159.
[3] LAVIE D,BEN-SHMUEL A,EREZ N,et al.Cancer-associated fibroblasts in the single-cell era[J].Nat Cancer,2022,3(7):793-807.
[4] CHEN Y,MCANDREWS KM,KALLURI R.Clinical and therapeutic relevance of cancer-associated fibroblasts[J].Nat Rev Clin Oncol,2021,18(12):792-804.
[5] 张世杰,蒋进勋,王启灵,等.肿瘤相关成纤维细胞在肿瘤中的研究进展[J].现代肿瘤医学,2023,31(22):4267-4272. ZHANG SJ,JIANG JX,WANG QN,et al.Research progress of tumor-associated fibroblasts in tumors[J].Modern Oncology,2023,31(22):4267-4272.
[6] SAHAI E,ASTSATUROV I,CUKIERMAN E,et al.A framework for advancing our understanding of cancer-associated fibroblasts[J].Nat Rev Cancer,2020,20(3):174-186.
[7] FIORI ME,DI FRANCO S,VILLANOVA L,et al.Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance[J].Mol Cancer,2019,18(1):70.
[8] WATABE T,TAKAHASHI K,PIETRAS K,et al.Roles of TGF-beta signals in tumor microenvironment via regulation of the formation and plasticity of vascular system[J].Semin Cancer Biol,2023,92:130-138.
[9] VAN DEN BULK J,DE MIRANDA N,TEN DIJKE P.Therapeutic targeting of TGF-beta in cancer:hacking a master switch of immune suppression[J].Clin Sci (Lond),2021,135(1):35-52.
[10] WU J,JING X,DU Q,et al.Disruption of the clock component Bmal1 in mice promotes cancer metastasis through the PAI-1-TGF-beta-myoCAF-dependent mechanism[J].Adv Sci (Weinh),2023,10(24):e2301505.
[11] ZHANG H,CHEN J,BAI J,et al.Single dual-specific anti-PD-L1/TGF-beta antibody synergizes with chemotherapy as neoadjuvant treatment for pancreatic ductal adenocarcinoma:a preclinical experimental study[J].Int J Surg,2024,110(5):2679-2691.
[12] KOBAYASHI M,FUJIWARA K,TAKAHASHI K,et al.Transforming growth factor-beta-induced secretion of extracellular vesicles from oral cancer cells evokes endothelial barrier instability via endothelial-mesenchymal transition[J].Inflamm Regen,2022,42(1):38.
[13] CHUNG JY,CHAN MK,LI JS,et al.TGF-beta signaling:From tissue fibrosis to tumor microenvironment[J].Int J Mol Sci,2021,22(14):7575.
[14] DAUER P,ZHAO X,GUPTA VK,et al.Inactivation of cancer-associated-fibroblasts disrupts oncogenic signaling in pancreatic cancer cells and promotes its regression[J].Cancer Res,2018,78(5):1321-1333.
[15] MIAO L,LIU Q,LIN CM,et al.Targeting tumor-associated fibroblasts for therapeutic delivery in desmoplastic tumors[J].Cancer Res,2017,77(3):719-731.
[16] ZHAO Y,JIA Y,WANG J,et al.circNOX4 activates an inflammatory fibroblast niche to promote tumor growth and metastasis in NSCLC via FAP/IL-6 axis[J].Mol Cancer,2024,23(1):47.
[17] ZHAO L,CHEN J,PANG Y,et al.Fibroblast activation protein-based theranostics in cancer research:A state-of-the-art review[J].Theranostics,2022,12(4):1557-1569.
[18] ROY J,HETTIARACHCHI SU,KAAKE M,et al.Design and validation of fibroblast activation protein alpha targeted imaging and therapeutic agents[J].Theranostics,2020,10(13):5778-5789.
[19] SYED M,FLECHSIG P,LIERMANN J,et al.Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers[J].Eur J Nucl Med Mol Imaging,2020,47(12):2836-2845.
[20] FABRE M,FERRER C,DOMINGUEZ-HORMAETXE S,et al.OMTX705,a novel FAP-targeting ADC demonstrates activity in chemotherapy and pembrolizumab-resistant solid tumor models[J].Clin Cancer Res,2020,26(13):3420-3430.
[21] LOUREIRO LR,HOFFMANN L,NEUBER C,et al.Immunotheranostic target modules for imaging and navigation of UniCAR T-cells to strike FAP-expressing cells and the tumor microenvironment[J].J Exp Clin Cancer Res,2023,42(1):341.
[22] KAHOUNOVA Z,KURFURSTOVA D,BOUCHAL J,et al.The fibroblast surface markers FAP,anti-fibroblast,and FSP are expressed by cells of epithelial origin and may be altered during epithelial-to-mesenchymal transition[J].Cytometry A,2018,93(9):941-951.
[23] NURMIK M,ULLMANN P,RODRIGUEZ F,et al.In search of definitions:Cancer-associated fibroblasts and their markers[J].Int J Cancer,2020,146(4):895-905.
[24] MUCHLINSKA A,NAGEL A,POPEDA M,et al.Alpha-smooth muscle actin-positive cancer-associated fibroblasts secreting osteopontin promote growth of luminal breast cancer[J].Cell Mol Biol Lett,2022,27(1):45.
[25] LAI SW,CHENG YC,KIU KT,et al.PROX1 interaction with alpha-SMA-rich cancer-associated fibroblasts facilitates colorectal cancer progression and correlates with poor clinical outcomes and therapeutic resistance[J].Aging (Albany NY),2024,16(2):1620-1639.
[26] WANG Z,HAN S,XU K,et al.alpha-SMA(+) cancer-associated fibroblasts increased tumor enhancement ratio on contrast-enhanced multidetector-row computed tomography in stages Ⅰ-Ⅲ colon cancer[J].J Gastroenterol Hepatol,2023,38(12):2111-2121.
[27]OZDEMIR BC,PENTCHEVA-HOANG T,CARSTENS JL,et al.Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival[J].Cancer Cell,2015,28(6):831-833.
[28] PATEL AK,VIPPARTHI K,THATIKONDA V,et al.A subtype of cancer-associated fibroblasts with lower expression of alpha-smooth muscle actin suppresses stemness through BMP4 in oral carcinoma[J].Oncogenesis,2018,7(10):78.
[29] SU S,CHEN J,YAO H,et al.CD10(+)GPR77(+) cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness[J].Cell,2018,172(4):841-856 e816.
[30] ZHAO Z,ZHU Y.FAP,CD10,and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer[J].BMC Cancer,2023,23(1):507.
[31]TONG Y,ZHAO Z,ZHANG J,et al.High expressions of CD10,FAP and GPR77 in CAFs are associated with chemoresistance and worse prognosis in gastric cancer[J].Front Oncol,2022,12:984817.
[32] BARRETT R,PURE E.Cancer-associated fibroblasts:key determinants of tumor immunity and immunotherapy[J].Curr Opin Immunol,2020,64:80-87.
[33] ZHANG A,QIAN Y,YE Z,et al.Cancer-associated fibroblasts promote M2 polarization of macrophages in pancreatic ductal adenocarcinoma[J].Cancer Med,2017,6(2):463-470.
[34] LI L,WEN Q,DING R.Therapeutic targeting of VEGF and/or TGF-beta to enhance anti-PD-(L)1 therapy:The evidence from clinical trials[J].Front Oncol,2022,12:905520.
[35] HUANG TX,TAN XY,HUANG HS,et al.Targeting cancer-associated fibroblast-secreted WNT2 restores dendritic cell-mediated antitumour immunity[J].Gut,2022,71(2):333-344.
[36] UNTERLEUTHNER D,NEUHOLD P,SCHWARZ K,et al.Cancer-associated fibroblast-derived WNT2 increases tumor angiogenesis in colon cancer[J].Angiogenesis,2020,23(2):159-177.
[37]陶明珠,胡书娅,郭庆喜,等.肝细胞癌组织中肿瘤相关成纤维细胞与血管生成拟态的相关性及临床意义[J].现代肿瘤医学,2019,27(23):4234-4237. TAO MZ,HU SY,GUO QX,et al.Correlation between cancer associated fibroblasts and vasculogenic mimicry in hepatocellular carcinoma and its clinical significance[J].Modern Oncology,2019,27(23):4234-4237.
[38]HUANG T,LI F,CHENG X,et al.Wnt inhibition sensitizes PD-L1 blockade therapy by overcoming bone marrow-derived myofibroblasts-mediated immune resistance in tumors[J].Front Immunol,2021,12:619209.
[39] PAOLILLO M,SCHINELLI S.Extracellular matrix alterations in metastatic processes[J].Int J Mol Sci,2019,20(19):4947.
[40] CISZEWSKI WM,WAWRO ME,SACEWICZ-HOFMAN I,et al.Cytoskeleton reorganization in endmt-the role in cancer and fibrotic diseases[J].Int J Mol Sci,2021,22(21):11607.
[41]LI DK,CHEN XR,WANG LN,et al.Exosomal HMGA2 protein from EBV-positive NPC cells destroys vascular endothelial barriers and induces endothelial-to-mesenchymal transition to promote metastasis[J].Cancer Gene Ther,2022,29(10):1439-1451.
[42]LANG J,ZHAO X,QI Y,et al.Reshaping prostate tumor microenvironment to suppress metastasis via cancer-associated fibroblast inactivation with peptide-assembly-based nanosystem[J].ACS Nano,2019,13(11):12357-12371.

Memo

Memo:
-
Last Update: 1900-01-01