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Therapeutic Drugs And Drug Delivery Systems Targeting Stromal Cells For Cancer Therapy: A Review

Zhaohuan Li, Zengjuan Zheng, Chenglei Li, Zhi-peng Li, Jing-liang Wu, B. Zhang
Published 2020 · Medicine

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Abstract Tumour microenvironment provides the ‘soil’ for tumour growth. Besides tumour cells, there are also numbers of stromal cells, extracellular matrix and other components in the tumour microenvironment. In the past years, kinds of ligands and markers specifically high-expressed on the surface of the tumour stromal cells have been explored, which can be used as the therapeutic targets for cancer treatment. Recently, the antitumor drugs by targeting stromal cells, including small-molecular inhibitor and large-molecular monoclonal antibody, have been widely discovered and applied in clinic attributed to their specific targeting ability. Moreover, the targeted drug delivery system also paid more and more attentions due to their desired profiles in increased accumulation at tumour sites, enhanced antitumor ability and less toxicity and side effects. Therefore, it is of great significance to find and construct drug delivery systems targeting tumour stromal cells. In this review, we discussed the widely recognised therapeutic targets on tumour stromal cells, besides, the current status on the targeting drugs as well as the drug delivery systems were also highlighted.
This paper references
10.1158/1078-0432.CCR-07-0588
Cancer Vaccines: Moving Beyond Current Paradigms
J. Schlom (2007)
10.18632/ONCOTARGET.2998
Classification of current anticancer immunotherapies
L. Galluzzi (2014)
10.1039/c7md00391a
Cancer nanomedicine: from PDGF targeted drug delivery.
C. Rejeeth (2017)
10.1002/adma.201404715
Peptide assembly integration of fibroblast-targeting and cell-penetration features for enhanced antitumor drug delivery.
T. Ji (2015)
10.7150/thno.14858
The Smart Drug Delivery System and Its Clinical Potential
Dong Liu (2016)
10.1016/j.semcancer.2012.02.002
Differentiation and gene expression profile of tumor-associated macrophages.
A. Schmieder (2012)
10.1016/j.coi.2011.12.009
Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity.
Suzanne L. Topalian (2012)
10.1111/j.1600-065X.2009.00770.x
CD28 and CTLA‐4 coreceptor expression and signal transduction
C. Rudd (2009)
10.1158/1535-7163.MCT-14-0983
PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy
S. Patel (2015)
10.1016/J.COPBIO.2004.10.005
Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs.
D. Felnerova (2004)
10.1002/jps.24290
Replacing heme with paclitaxel to prepare drug-loaded globin nanoassembles for CD163 targeting.
Zhengjie Meng (2015)
A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer.
A. Scott (2003)
10.1208/s12249-019-1385-0
Dual-Ligand Modification of PEGylated Liposomes Used for Targeted Doxorubicin Delivery to Enhance Anticancer Efficacy
Cong Li (2019)
10.1093/cid/ciy175
Serious Infections in Patients Receiving Ibrutinib for Treatment of Lymphoid Cancer
Tilly A Varughese (2018)
10.1038/bjc.2013.768
Cancer-associated fibroblasts induce epithelial–mesenchymal transition of breast cancer cells through paracrine TGF-β signalling
Y. Yu (2014)
10.1186/1478-811X-9-18
Interaction of tumor cells with the microenvironment
H. Ungefroren (2011)
10.1111/j.1349-7006.2007.00704.x
Understanding tumor endothelial cell abnormalities to develop ideal anti‐angiogenic therapies
K. Hida (2008)
10.1021/acs.molpharmaceut.9b00261
Targeted Delivery of Zoledronate to Tumor-Associated Macrophages for Cancer Immunotherapy.
Xinlong Zang (2019)
10.1124/JPET.105.084145
Role of Tyrosine Kinase Inhibitors in Cancer Therapy
A. Arora (2005)
10.1016/S0304-4165(02)00319-7
The mannose receptor family.
L. East (2002)
10.1038/nrc3627
VEGF targets the tumour cell
H. L. Goel (2013)
10.1111/cts.12648
Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma
S. Pisano (2019)
10.1172/JCI76094
Targeting cancer with kinase inhibitors.
S. Gross (2015)
10.1021/acs.bioconjchem.9b00206
Development of a Cross-Reactive Monoclonal Antibody for Detecting the Tumor Stroma.
Hallie M Hintz (2019)
10.18632/oncotarget.20244
CD163 as a novel target gene of STAT3 is a potential therapeutic target for gastric cancer
Zhenguo Cheng (2017)
10.1002/adma.201705436
Dimeric Drug Polymeric Micelles with Acid-Active Tumor Targeting and FRET-Traceable Drug Release.
Xing Guo (2018)
10.3109/1061186X.2015.1051049
Nanocarriers for cancer-targeted drug delivery
P. Kumari (2016)
10.1002/ijc.27506
Tumor‐promoting macrophages induce the expression of the macrophage‐specific receptor CD163 in malignant cells
Maciej Bogdan Maniecki (2012)
10.1016/j.canlet.2008.10.037
Metastasis promoter S100A4 is a potentially valuable molecular target for cancer therapy.
G. Sherbet (2009)
10.1517/17425247.2013.729576
Theranostic liposomes for cancer diagnosis and treatment: current development and pre-clinical success
M. Muthu (2013)
10.1016/S1470-2045(15)70054-9
Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.
N. Rizvi (2015)
10.1002/smll.201702994
Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for Synergism of Photothermal Therapy and Chemotherapy.
Yi Wang (2018)
10.1016/j.pmatsci.2019.100599
Multifunctional nanoplatforms for subcellular delivery of drugs in cancer therapy
Xing Guo (2020)
10.2741/3613
Cancer associated fibroblasts (CAFs) in tumor microenvironment.
F. Xing (2010)
10.1016/j.semcancer.2010.04.005
Selectins promote tumor metastasis.
H. Läubli (2010)
10.1016/B978-0-12-386503-8.00006-5
Role of the VEGF/VEGFR axis in cancer biology and therapy.
A. Rapisarda (2012)
10.1158/1078-0432.CCR-18-0566
FDA's Approval of the First Biosimilar to Bevacizumab
S. Casak (2018)
10.1158/0008-5472.CAN-12-0122
Tumor microenvironment complexity: emerging roles in cancer therapy.
M. Swartz (2012)
10.1007/s00109-013-1021-5
The metastasis-promoting roles of tumor-associated immune cells
H. A. Smith (2013)
10.1007/s00262-014-1576-1
Modulation of the myeloid compartment of the immune system by angiogenic- and kinase inhibitor-targeted anti-cancer therapies
C. Castelli (2014)
10.1158/1078-0432.CCR-16-0663
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma
Meredith K. Chuk (2017)
10.1016/j.lfs.2015.02.025
P-selectin enhances growth and metastasis of mouse mammary tumors by promoting regulatory T cell infiltration into the tumors.
T. Nasti (2015)
10.1016/j.nano.2019.02.015
Integrin-targeted AmpRGD sunitinib liposomes as integrated antiangiogenic tools.
F. Bianchini (2019)
10.1021/nn800072t
Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery.
M. Liong (2008)
10.7150/thno.19365
Strategies for Preparing Albumin-based Nanoparticles for Multifunctional Bioimaging and Drug Delivery
F. An (2017)
10.1002/jcp.26094
Mesenchymal stem cells: A new platform for targeting suicide genes in cancer
Rana Moradian Tehrani (2018)
10.5732/cjc.012.10280
Small interfering RNA-based molecular therapy of cancers
W. Guo (2013)
10.1021/ja5122809
Enhanced NIR radiation-triggered hyperthermia by mitochondrial targeting.
H. S. Jung (2015)
10.1158/0008-5472.CAN-11-2994
Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages.
K. Movahedi (2012)
10.1016/j.fitote.2010.05.001
Applications of novel drug delivery system for herbal formulations.
Ajazuddin (2010)
10.1080/21691401.2017.1376675
Recent advances in co-delivery systems based on polymeric nanoparticle for cancer treatment
M. Afsharzadeh (2018)
10.1186/1471-2407-11-245
FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells
H. Lee (2010)
10.1038/nature12626
Influence of tumour micro-environment heterogeneity on therapeutic response
Melissa R. Junttila (2013)
10.1111/1523-1747.EP12338501
Genes encoding structural proteins of epidermal cornification and S100 calcium-binding proteins form a gene complex ("epidermal differentiation complex") on human chromosome 1q21.
D. Mischke (1996)
10.3390/ijms20040840
Targeting Tumor Microenvironment for Cancer Therapy
C. Roma-Rodrigues (2019)
10.1038/nm.3394
Microenvironmental regulation of tumor progression and metastasis
Daniela F. Quail (2013)
10.1016/j.colsurfb.2014.12.041
Nanotechnological carriers for cancer chemotherapy: the state of the art.
M. Estanqueiro (2015)
10.1007/S11912-007-0007-2
Pazopanib: A novel multitargeted tyrosine kinase inhibitor
G. Sonpavde (2007)
10.1016/j.tcb.2014.12.006
Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance.
L. Seguin (2015)
10.1016/S1535-6108(03)00089-8
PDGF receptors as cancer drug targets.
K. Pietras (2003)
10.1038/nrc2748
Integrins in cancer: biological implications and therapeutic opportunities
J. S. Desgrosellier (2010)
10.1002/anie.201506262
Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer‐Associated Fibroblast Activation
T. Ji (2016)
10.1158/1078-0432.CCR-15-0600
FDA Approval Summary: Ramucirumab for Gastric Cancer
S. Casak (2015)
10.1016/j.jconrel.2016.09.014
Comprehensively priming the tumor microenvironment by cancer-associated fibroblast-targeted liposomes for combined therapy with cancer cell-targeted chemotherapeutic drug delivery system.
B. Chen (2016)
10.1016/j.biopha.2017.10.058
The role of pazopanib on tumour angiogenesis and in the management of cancers: A review.
Dinesh Kumar Chellappan (2017)
10.1038/nm0302-193
Integrin-mediated death: An explanation of the integrin-knockout phenotype?
David A. Cheresh (2002)
10.18632/oncotarget.20160
Tenascin-C induces migration and invasion through JNK/c-Jun signalling in pancreatic cancer
J. Cai (2017)
10.1634/theoncologist.2015-0507
FDA Approval Summary: Nivolumab for the Treatment of Metastatic Non-Small Cell Lung Cancer With Progression On or After Platinum-Based Chemotherapy
D. Kazandjian (2016)
10.1007/s11307-017-1048-z
Validation of Bevacizumab Therapy Effect on Colon Cancer Subtypes by Using Whole Body Imaging in Mice
I. Vuletic (2017)
10.1038/nrc3236
Antibody therapy of cancer
Andrew M. Scott (2012)
10.1007/s10585-015-9723-4
Fibroblast activation protein increases metastatic potential of fibrosarcoma line HT1080 through upregulation of integrin-mediated signaling pathways
S. Baird (2015)
10.1038/s41573-018-0004-1
Turning foes to friends: targeting cancer-associated fibroblasts
Xueman Chen (2018)
10.1007/s12032-010-9515-2
High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation
Chuan-Yong Mu (2011)
10.1517/13543780902997928
Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer
R. Madan (2009)
10.1016/j.cell.2009.12.046
Autocrine VEGF Signaling Synergizes with EGFR in Tumor Cells to Promote Epithelial Cancer Development
Beate M Lichtenberger (2010)
10.2217/fon.15.52
Nivolumab: targeting PD-1 to bolster antitumor immunity.
J. Brahmer (2015)
10.1016/j.ajg.2017.05.013
Dendritic cell-based cancer immunotherapy for pancreatic cancer.
W. Li (2018)
10.1093/jnci/djs033
Therapeutic cancer vaccines: current status and moving forward.
J. Schlom (2012)
10.2147/IJN.S103556
Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity
Y. Liu (2016)
10.1634/theoncologist.2014-0465
Targeting Angiogenesis in Cancer Therapy: Moving Beyond Vascular Endothelial Growth Factor.
Y. Zhao (2015)
10.7150/thno.30716
Exosomes from M1-Polarized Macrophages Enhance Paclitaxel Antitumor Activity by Activating Macrophages-Mediated Inflammation
P. Wang (2019)
10.3390/ijms20092256
Activated Fibroblast Program Orchestrates Tumor Initiation and Progression; Molecular Mechanisms and the Associated Therapeutic Strategies
G. Yoshida (2019)
10.1155/2014/180549
Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy
Warangkana Lohcharoenkal (2014)
10.1016/j.molmed.2013.05.002
Multifarious functions of PDGFs and PDGFRs in tumor growth and metastasis.
Y. Cao (2013)
10.3109/21691401.2014.998830
The use of nanoparticles as a promising therapeutic approach in cancer immunotherapy
M. Hosseini (2016)
10.1200/JCO.2012.42.7906
Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.
R. Advani (2013)
10.1186/s40425-018-0321-2
Ipilimumab induced digital vasculitis
Amrita Padda (2018)
10.1016/j.drudis.2015.07.008
Small-molecule kinase inhibitors: an analysis of FDA-approved drugs.
P. Wu (2016)
10.1634/theoncologist.2012-0044
FDA approval summary: sunitinib for the treatment of progressive well-differentiated locally advanced or metastatic pancreatic neuroendocrine tumors.
G. Blumenthal (2012)
10.1016/j.jconrel.2010.08.027
To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery.
F. Danhier (2010)
10.1021/acs.nanolett.6b04150
Protein Nanocage Mediated Fibroblast-Activation Protein Targeted Photoimmunotherapy To Enhance Cytotoxic T Cell Infiltration and Tumor Control.
Zipeng Zhen (2017)
10.3892/ijo.2010.861
Selective inhibition of PDGFR by imatinib elicits the sustained activation of ERK and downstream receptor signaling in malignant glioma cells.
Yucui Dong (2011)
10.1016/j.ijpharm.2017.03.034
Targeted delivery of epirubicin to tumor-associated macrophages by sialic acid-cholesterol conjugate modified liposomes with improved antitumor activity.
Songlei Zhou (2017)
10.1016/j.nano.2015.10.001
A tenascin C targeted nanoliposome with navitoclax for specifically eradicating of cancer-associated fibroblasts.
B. Chen (2016)
10.18632/oncotarget.13220
Lung tissue remodelling in MCT-induced pulmonary hypertension: a proposal for a novel scoring system and changes in extracellular matrix and fibrosis associated gene expression
M. Franz (2016)
10.1016/j.ctrv.2015.11.003
Lenvatinib: Role in thyroid cancer and other solid tumors.
M. Cabanillas (2016)
10.1158/2326-6066.CIR-13-0127
PD-L1 Expression in Triple-Negative Breast Cancer
E. A. Mittendorf (2014)
10.1016/j.semcancer.2008.03.004
Macrophage polarization in tumour progression.
A. Sica (2008)
10.2147/OTT.S189391
Ponatinib: a novel multi-tyrosine kinase inhibitor against human malignancies
Fiona D. H. Tan (2019)
10.1615/CRITREVIMMUNOL.V30.I6.30
Endothelial cells as key determinants of the tumor microenvironment: interaction with tumor cells, extracellular matrix and immune killer cells.
S. Chouaib (2010)
10.1007/s10555-007-9101-z
The selectin–selectin ligand axis in tumor progression
I. Witz (2007)
10.1093/carcin/bgp248
MMP13 as a stromal mediator in controlling persistent angiogenesis in skin carcinoma.
Wiltrud Lederle (2010)
10.1080/1061186X.2018.1519029
Stimuli-responsive nanoscale drug delivery systems for cancer therapy
L. Li (2019)
10.3390/cancers11020189
Tumor-Associated Macrophages Induce Endocrine Therapy Resistance in ER+ Breast Cancer Cells
Andrés M. Castellaro (2019)
10.1056/NEJMoa1215637
Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.
J. Byrd (2013)
10.2174/138920109787315088
Targeting the tumor stroma in cancer therapy.
K. Anton (2009)
10.1039/C6TB01823H
Peptide functionalized targeting liposomes: for nanoscale drug delivery towards angiogenesis.
Q. Han (2016)
10.1155/2014/357027
Imatinib: A Breakthrough of Targeted Therapy in Cancer
N. Iqbal (2014)
10.1182/blood-2008-10-186585
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes.
H. Läubli (2009)
10.1016/0888-7543(95)80005-7
Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium-binding protein family.
B. Schäfer (1995)
10.1186/s40364-019-0159-x
Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm
Kan Yin (2019)
10.1016/j.biomaterials.2017.10.012
Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy.
Tian Tian (2018)
10.1097/HJH.0000000000002067
Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation.
Patricio Araos (2019)
10.1146/annurev-pharmtox-010715-103633
RNA Interference (RNAi)-Based Therapeutics: Delivering on the Promise?
Maggie L. Bobbin (2016)
10.1158/1078-0432.CCR-14-2225
FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia
R. A. de Claro (2015)
10.1101/SQB.2005.70.007
The fibroblastic coconspirator in cancer progression.
M. Egeblad (2005)
10.2217/fon.15.322
Axitinib for the treatment of metastatic renal cell carcinoma.
Hiral Parekh (2016)
10.1038/nri2744
Monoclonal antibodies: versatile platforms for cancer immunotherapy
L. Weiner (2010)
10.3109/1061186X.2015.1073295
Nanomedicine and cancer immunotherapy – targeting immunosuppressive cells
Fernando Torres Andón (2015)
10.3109/1061186X.2014.921925
Polymeric micelles for pH-responsive delivery of cisplatin
M. Shahin (2014)
10.1158/2326-6066.CIR-15-0044
CTLA-4 Blockade Synergizes Therapeutically with PARP Inhibition in BRCA1-Deficient Ovarian Cancer
T. Higuchi (2015)
10.1038/ni.2703
Innate and adaptive immune cells in the tumor microenvironment
T. Gajewski (2013)
10.1159/000069863
Stromal Antigen Targeting by a Humanised Monoclonal Antibody: An Early Phase II Trial of Sibrotuzumab in Patients with Metastatic Colorectal Cancer
R. Hofheinz (2003)
10.1016/j.febslet.2004.05.022
A mechanism of impaired mobility of oligodendrocyte progenitor cells by tenascin C through modification of wnt signaling
Y. Kakinuma (2004)
10.1016/j.biomaterials.2014.05.091
Quantitative control of active targeting of nanocarriers to tumor cells through optimization of folate ligand density.
Zhaomin Tang (2014)
10.1080/10611860600809112
Liposomes as targeted drug delivery systems in the treatment of breast cancer
G. Sharma (2006)
10.1080/21691401.2016.1178136
Application of nanostructured drug delivery systems in immunotherapy of cancer: a review
Nahideh Asadi (2017)
10.3390/ijms16035254
Development of Small RNA Delivery Systems for Lung Cancer Therapy
Y. Fujita (2015)
10.1159/000484102
Long-Term Imatinib Treatment for Patients with Unresectable or Recurrent Gastrointestinal Stromal Tumors
K. Ogata (2018)
10.1016/j.biomaterials.2013.11.083
A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy.
Y. Tian (2014)
10.1093/jb/mvs136
Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases.
M. Shibuya (2013)
10.1038/nrd1381
Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer
N. Ferrara (2004)
10.1016/j.jconrel.2011.06.004
Inorganic nanoparticles for cancer imaging and therapy.
Huang-Chiao Huang (2011)
10.1016/j.semcdb.2009.11.017
Origin and function of tumor stroma fibroblasts.
Georgia Xouri (2010)
10.1080/1061186X.2019.1648478
Role of therapeutic agents on repolarisation of tumour-associated macrophage to halt lung cancer progression
Hibah M Aldawsari (2019)
10.1021/acs.molpharmaceut.7b00649
Nuclear and Fluorescent Labeled PD-1-Liposome-DOX-64Cu/IRDye800CW Allows Improved Breast Tumor Targeted Imaging and Therapy.
Y. Du (2017)
10.1016/j.it.2014.12.001
Confusing signals: Recent progress in CTLA-4 biology
L. Walker (2015)
10.1039/C3TB21238F
Liposome-like Nanostructures for Drug Delivery.
W. Gao (2013)
10.1080/21691401.2019.1687501
AuNPs as an important inorganic nanoparticle applied in drug carrier systems
W. Li (2019)
10.1021/acs.molpharmaceut.6b01068
Vitamin E Succinate-Grafted-Chitosan Oligosaccharide/RGD-Conjugated TPGS Mixed Micelles Loaded with Paclitaxel for U87MG Tumor Therapy.
Yanzuo Chen (2017)



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