Versatility of Cancer Associated Fibroblasts: Commendable Targets for Anti-tumor Therapy

被引:33
作者
Khan, Ghulam Jilany [1 ,2 ,3 ]
Sun, Li [4 ]
Khan, Sara [5 ]
Yuan, Shengtao [3 ]
He Nongyue [1 ]
机构
[1] Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China
[2] Univ Cent Punjab, Fac Pharm, Dept Pharmacol & Therapeut, Lahore, Pakistan
[3] China Pharmaceut Univ, Jiangsu Ctr Pharmacodynam Res & Evaluat, Nanjing 210009, Jiangsu, Peoples R China
[4] China Pharmaceut Univ, Jiangsu Key Lab Drug Screening, Nanjing 210009, Jiangsu, Peoples R China
[5] Univ Punjab PU, Univ Coll Pharm, Lahore, Pakistan
关键词
Tumor microenvironment; hypoxia; synergetic effect; genetic stability; biomarkers; drug resistance; anti immunosupportive; TUMOR-ASSOCIATED FIBROBLASTS; ENDOTHELIAL GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; HUMAN BRAIN-TUMOR; BONE-MARROW; TGF-BETA; BREAST-CANCER; STROMAL FIBROBLASTS; ACTIVATION PROTEIN; EXTRACELLULAR-MATRIX;
D O I
10.2174/1389450119666180219124439
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background and Objective: Tumor growth, development, progression, metastasis, invasion and resistivity against drugs solely depend on the recruitment of surrounding cells, extracellular matrix and Tumor Microenvironment (TME). TME is directly as well as indirectly associated with CancerAssociated Fibroblasts (CAF). The interactions of CAF with tumor surrounding cells, their origination, activation, transformation and ability to recruit other non-tumor cells for the clemency of tumor, are very complex and under active research since long. This study provides an in-depth review of CAF and highlights its potential targets for the regulation of TME as well as discusses current drugs in clinical trials, targeting through CAF. Conclusion: The potential role of CAF in anti-tumor therapy is based on its coherent response against drugs, targeting different tumor sections through these genetically more stable and anti-immunosupportive CAF cells. CAF can be targeted through immunity system; Growth Factors (GF) including Transforming growth factor (TGF), vascular endothelial GF, fibroblast GF, platelet derived GF; and TME elements including hypoxia, carbonic anhydrase, extracellular matrix (ECM). Collectively these features of CAF make it most vulnerable against single as well as combinational, anti-tumor therapy for synergistic or additive effects. Potential activities of CAF, their origination mechanisms and identification of meticulous bio-markers are needed to be investigated further. The rousing facts about them mutually culminate the anticipation of progress towards novel therapeutic establishment against cancer through CAFs that are under progressive research at all levels including, pre-clinical and clinical trials as well as possess much potential to be explored further.
引用
收藏
页码:1573 / 1588
页数:16
相关论文
共 204 条
  • [11] Banales Asurmendi JM, U. S. Patent, Patent No. [14/647,755, 647755]
  • [12] Barcellos-Hoff MH, 2000, CANCER RES, V60, P1254
  • [13] Methylation determines fibroblast activation and fibrogenesis in the kidney
    Bechtel, Wibke
    McGoohan, Scott
    Zeisberg, Elisabeth M.
    Mueller, Gerhard A.
    Kalbacher, Hubert
    Salant, David J.
    Mueller, Claudia A.
    Kalluri, Raghu
    Zeisberg, Michael
    [J]. NATURE MEDICINE, 2010, 16 (05) : 544 - U75
  • [14] Bevacizumab plus irinotecan-, fluorouracil-, and leucovorin-based chemotherapy with concomitant HAART in an HIV-positive patient with metastatic colorectal cancer
    Berretta, Massimiliano
    Lleshi, Arben
    Zanet, Ernesto
    Bearz, Alessandra
    Simonelli, Cecilia
    Fisichella, Rossella
    Nasti, Guglielmo
    Berretta, Salvatore
    Tirelli, Umberto
    [J]. ONKOLOGIE, 2008, 31 (07): : 394 - 397
  • [15] SOM230 (Pasireotide) and Temozolomide Achieve Sustained Control of Tumour Progression and ACTH Secretion in Pituitary Carcinoma with Widespread Metastases
    Bode, H.
    Seiz, M.
    Lammert, A.
    Brockmann, M. A.
    Back, W.
    Hammes, H. -P.
    Thome, C.
    [J]. EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 2010, 118 (10) : 760 - 763
  • [16] Cancer-Associated Fibroblasts Share Characteristics and Protumorigenic Activity with Mesenchymal Stromal Cells
    Borriello, Lucia
    Nakata, Rie
    Sheard, Michael A.
    Fernandez, G. Esteban
    Sposto, Richard
    Malvar, Jemily
    Blavier, Laurence
    Shimada, Hiroyuki
    Asgharzadeh, Shahab
    Seeger, Robert C.
    DeClerck, Yves A.
    [J]. CANCER RESEARCH, 2017, 77 (18) : 5142 - 5157
  • [17] Arousal of Cancer-Associated Stroma: Overexpression of Palladin Activates Fibroblasts to Promote Tumor Invasion
    Brentnall, Teresa A.
    Lai, Lisa A.
    Coleman, Joshua
    Bronner, Mary P.
    Pan, Sheng
    Chen, Ru
    [J]. PLOS ONE, 2012, 7 (01):
  • [18] Targeting leukocyte MMPs and transmigration - Minocycline as a potential therapy for multiple sclerosis
    Brundula, V
    Rewcastle, NB
    Metz, LM
    Bernard, CC
    Yong, VW
    [J]. BRAIN, 2002, 125 : 1297 - 1308
  • [19] Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia
    Burger, J. A.
    Tedeschi, A.
    Barr, P. M.
    Robak, T.
    Owen, C.
    Ghia, P.
    Bairey, O.
    Hillmen, P.
    Bartlett, N. L.
    Li, J.
    Simpson, D.
    Grosicki, S.
    Devereux, S.
    McCarthy, H.
    Coutre, S.
    Quach, H.
    Gaidano, G.
    Maslyak, Z.
    Stevens, D. A.
    Janssens, A.
    Offner, F.
    Mayer, J.
    O'Dwyer, M.
    Hellmann, A.
    Schuh, A.
    Siddiqi, T.
    Polliack, A.
    Tam, C. S.
    Suri, D.
    Cheng, M.
    Clow, F.
    Styles, L.
    James, D. F.
    Kipps, T. J.
    Keating, Michael
    Jen, Jie
    Jindra, Pavel
    Simkovic, Martin
    Braester, Andrei
    Ruchlemer, Rosa
    Foa, Roberto
    Semenzato, Gianpietro
    Hawkins, Timothy
    Atanasio, Carolina Moreno
    Demirkan, Fatih
    Kaynar, Leylagul
    Pylypenko, Halyna
    Fox, Christopher
    Thirman, Michael
    Campbell, Philip
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (25) : 2425 - 2437
  • [20] A perivascular niche for brain tumor stem cells
    Calabrese, Christopher
    Poppleton, Helen
    Kocak, Mehmet
    Hogg, Twala L.
    Fuller, Christine
    Hamner, Blair
    Oh, Eun Young
    Gaber, M. Waleed
    Finklestein, David
    Allen, Meredith
    Frank, Adrian
    Bayazitov, Ildar T.
    Zakharenko, Stanislav S.
    Gajjar, Amar
    Davidoff, Andrew
    Gilbertson, Richard J.
    [J]. CANCER CELL, 2007, 11 (01) : 69 - 82