Please confirm you are human (Sign Up for free to never see this)
← Back to Search
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
Save to my Library
Download PDFAnalyze on Scholarcy
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
Cancer Vaccines: Moving Beyond Current Paradigms
J. Schlom (2007)
Classification of current anticancer immunotherapies
L. Galluzzi (2014)
Cancer nanomedicine: from PDGF targeted drug delivery.
C. Rejeeth (2017)
Peptide assembly integration of fibroblast-targeting and cell-penetration features for enhanced antitumor drug delivery.
T. Ji (2015)
The Smart Drug Delivery System and Its Clinical Potential
Dong Liu (2016)
Differentiation and gene expression profile of tumor-associated macrophages.
A. Schmieder (2012)
Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity.
Suzanne L. Topalian (2012)
CD28 and CTLA‐4 coreceptor expression and signal transduction
C. Rudd (2009)
PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy
S. Patel (2015)
Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs.
D. Felnerova (2004)
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)
Dual-Ligand Modification of PEGylated Liposomes Used for Targeted Doxorubicin Delivery to Enhance Anticancer Efficacy
Cong Li (2019)
Serious Infections in Patients Receiving Ibrutinib for Treatment of Lymphoid Cancer
Tilly A Varughese (2018)
Cancer-associated fibroblasts induce epithelial–mesenchymal transition of breast cancer cells through paracrine TGF-β signalling
Y. Yu (2014)
Interaction of tumor cells with the microenvironment
H. Ungefroren (2011)
Understanding tumor endothelial cell abnormalities to develop ideal anti‐angiogenic therapies
K. Hida (2008)
Targeted Delivery of Zoledronate to Tumor-Associated Macrophages for Cancer Immunotherapy.
Xinlong Zang (2019)
Role of Tyrosine Kinase Inhibitors in Cancer Therapy
A. Arora (2005)
The mannose receptor family.
L. East (2002)
VEGF targets the tumour cell
H. L. Goel (2013)
Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma
S. Pisano (2019)
Targeting cancer with kinase inhibitors.
S. Gross (2015)
Development of a Cross-Reactive Monoclonal Antibody for Detecting the Tumor Stroma.
Hallie M Hintz (2019)
CD163 as a novel target gene of STAT3 is a potential therapeutic target for gastric cancer
Zhenguo Cheng (2017)
Dimeric Drug Polymeric Micelles with Acid-Active Tumor Targeting and FRET-Traceable Drug Release.
Xing Guo (2018)
Nanocarriers for cancer-targeted drug delivery
P. Kumari (2016)
Tumor‐promoting macrophages induce the expression of the macrophage‐specific receptor CD163 in malignant cells
Maciej Bogdan Maniecki (2012)
Metastasis promoter S100A4 is a potentially valuable molecular target for cancer therapy.
G. Sherbet (2009)
Theranostic liposomes for cancer diagnosis and treatment: current development and pre-clinical success
M. Muthu (2013)
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)
Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for Synergism of Photothermal Therapy and Chemotherapy.
Yi Wang (2018)
Multifunctional nanoplatforms for subcellular delivery of drugs in cancer therapy
Xing Guo (2020)
Cancer associated fibroblasts (CAFs) in tumor microenvironment.
F. Xing (2010)
Selectins promote tumor metastasis.
H. Läubli (2010)
Role of the VEGF/VEGFR axis in cancer biology and therapy.
A. Rapisarda (2012)
FDA's Approval of the First Biosimilar to Bevacizumab
S. Casak (2018)
Tumor microenvironment complexity: emerging roles in cancer therapy.
M. Swartz (2012)
The metastasis-promoting roles of tumor-associated immune cells
H. A. Smith (2013)
Modulation of the myeloid compartment of the immune system by angiogenic- and kinase inhibitor-targeted anti-cancer therapies
C. Castelli (2014)
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma
Meredith K. Chuk (2017)
P-selectin enhances growth and metastasis of mouse mammary tumors by promoting regulatory T cell infiltration into the tumors.
T. Nasti (2015)
Integrin-targeted AmpRGD sunitinib liposomes as integrated antiangiogenic tools.
F. Bianchini (2019)
Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery.
M. Liong (2008)
Strategies for Preparing Albumin-based Nanoparticles for Multifunctional Bioimaging and Drug Delivery
F. An (2017)
Mesenchymal stem cells: A new platform for targeting suicide genes in cancer
Rana Moradian Tehrani (2018)
Small interfering RNA-based molecular therapy of cancers
W. Guo (2013)
Enhanced NIR radiation-triggered hyperthermia by mitochondrial targeting.
H. S. Jung (2015)
Nanobody-based targeting of the macrophage mannose receptor for effective in vivo imaging of tumor-associated macrophages.
K. Movahedi (2012)
Applications of novel drug delivery system for herbal formulations.
Recent advances in co-delivery systems based on polymeric nanoparticle for cancer treatment
M. Afsharzadeh (2018)
FAP-overexpressing fibroblasts produce an extracellular matrix that enhances invasive velocity and directionality of pancreatic cancer cells
H. Lee (2010)
Influence of tumour micro-environment heterogeneity on therapeutic response
Melissa R. Junttila (2013)
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)
Targeting Tumor Microenvironment for Cancer Therapy
C. Roma-Rodrigues (2019)
Microenvironmental regulation of tumor progression and metastasis
Daniela F. Quail (2013)
Nanotechnological carriers for cancer chemotherapy: the state of the art.
M. Estanqueiro (2015)
Pazopanib: A novel multitargeted tyrosine kinase inhibitor
G. Sonpavde (2007)
Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance.
L. Seguin (2015)
PDGF receptors as cancer drug targets.
K. Pietras (2003)
Integrins in cancer: biological implications and therapeutic opportunities
J. S. Desgrosellier (2010)
Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer‐Associated Fibroblast Activation
T. Ji (2016)
FDA Approval Summary: Ramucirumab for Gastric Cancer
S. Casak (2015)
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)
The role of pazopanib on tumour angiogenesis and in the management of cancers: A review.
Dinesh Kumar Chellappan (2017)
Integrin-mediated death: An explanation of the integrin-knockout phenotype?
David A. Cheresh (2002)
Tenascin-C induces migration and invasion through JNK/c-Jun signalling in pancreatic cancer
J. Cai (2017)
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)
Validation of Bevacizumab Therapy Effect on Colon Cancer Subtypes by Using Whole Body Imaging in Mice
I. Vuletic (2017)
Antibody therapy of cancer
Andrew M. Scott (2012)
Fibroblast activation protein increases metastatic potential of fibrosarcoma line HT1080 through upregulation of integrin-mediated signaling pathways
S. Baird (2015)
Turning foes to friends: targeting cancer-associated fibroblasts
Xueman Chen (2018)
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)
Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer
R. Madan (2009)
Autocrine VEGF Signaling Synergizes with EGFR in Tumor Cells to Promote Epithelial Cancer Development
Beate M Lichtenberger (2010)
Nivolumab: targeting PD-1 to bolster antitumor immunity.
J. Brahmer (2015)
Dendritic cell-based cancer immunotherapy for pancreatic cancer.
W. Li (2018)
Therapeutic cancer vaccines: current status and moving forward.
J. Schlom (2012)
Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity
Y. Liu (2016)
Targeting Angiogenesis in Cancer Therapy: Moving Beyond Vascular Endothelial Growth Factor.
Y. Zhao (2015)
Exosomes from M1-Polarized Macrophages Enhance Paclitaxel Antitumor Activity by Activating Macrophages-Mediated Inflammation
P. Wang (2019)
Activated Fibroblast Program Orchestrates Tumor Initiation and Progression; Molecular Mechanisms and the Associated Therapeutic Strategies
G. Yoshida (2019)
Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy
Warangkana Lohcharoenkal (2014)
Multifarious functions of PDGFs and PDGFRs in tumor growth and metastasis.
Y. Cao (2013)
The use of nanoparticles as a promising therapeutic approach in cancer immunotherapy
M. Hosseini (2016)
Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.
R. Advani (2013)
Ipilimumab induced digital vasculitis
Amrita Padda (2018)
Small-molecule kinase inhibitors: an analysis of FDA-approved drugs.
P. Wu (2016)
FDA approval summary: sunitinib for the treatment of progressive well-differentiated locally advanced or metastatic pancreatic neuroendocrine tumors.
G. Blumenthal (2012)
To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery.
F. Danhier (2010)
Protein Nanocage Mediated Fibroblast-Activation Protein Targeted Photoimmunotherapy To Enhance Cytotoxic T Cell Infiltration and Tumor Control.
Zipeng Zhen (2017)
Selective inhibition of PDGFR by imatinib elicits the sustained activation of ERK and downstream receptor signaling in malignant glioma cells.
Yucui Dong (2011)
Targeted delivery of epirubicin to tumor-associated macrophages by sialic acid-cholesterol conjugate modified liposomes with improved antitumor activity.
Songlei Zhou (2017)
A tenascin C targeted nanoliposome with navitoclax for specifically eradicating of cancer-associated fibroblasts.
B. Chen (2016)
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)
Lenvatinib: Role in thyroid cancer and other solid tumors.
M. Cabanillas (2016)
PD-L1 Expression in Triple-Negative Breast Cancer
E. A. Mittendorf (2014)
Macrophage polarization in tumour progression.
A. Sica (2008)
Ponatinib: a novel multi-tyrosine kinase inhibitor against human malignancies
Fiona D. H. Tan (2019)
Endothelial cells as key determinants of the tumor microenvironment: interaction with tumor cells, extracellular matrix and immune killer cells.
S. Chouaib (2010)
The selectin–selectin ligand axis in tumor progression
I. Witz (2007)
MMP13 as a stromal mediator in controlling persistent angiogenesis in skin carcinoma.
Wiltrud Lederle (2010)
Stimuli-responsive nanoscale drug delivery systems for cancer therapy
L. Li (2019)
Tumor-Associated Macrophages Induce Endocrine Therapy Resistance in ER+ Breast Cancer Cells
Andrés M. Castellaro (2019)
Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.
J. Byrd (2013)
Targeting the tumor stroma in cancer therapy.
K. Anton (2009)
Peptide functionalized targeting liposomes: for nanoscale drug delivery towards angiogenesis.
Q. Han (2016)
Imatinib: A Breakthrough of Targeted Therapy in Cancer
N. Iqbal (2014)
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes.
H. Läubli (2009)
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)
Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm
Kan Yin (2019)
Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy.
Tian Tian (2018)
Dendritic cells are crucial for cardiovascular remodeling and modulate neutrophil gelatinase-associated lipocalin expression upon mineralocorticoid receptor activation.
Patricio Araos (2019)
RNA Interference (RNAi)-Based Therapeutics: Delivering on the Promise?
Maggie L. Bobbin (2016)
FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia
R. A. de Claro (2015)
The fibroblastic coconspirator in cancer progression.
M. Egeblad (2005)
Axitinib for the treatment of metastatic renal cell carcinoma.
Hiral Parekh (2016)
Monoclonal antibodies: versatile platforms for cancer immunotherapy
L. Weiner (2010)
Nanomedicine and cancer immunotherapy – targeting immunosuppressive cells
Fernando Torres Andón (2015)
Polymeric micelles for pH-responsive delivery of cisplatin
M. Shahin (2014)
CTLA-4 Blockade Synergizes Therapeutically with PARP Inhibition in BRCA1-Deficient Ovarian Cancer
T. Higuchi (2015)
Innate and adaptive immune cells in the tumor microenvironment
T. Gajewski (2013)
Stromal Antigen Targeting by a Humanised Monoclonal Antibody: An Early Phase II Trial of Sibrotuzumab in Patients with Metastatic Colorectal Cancer
R. Hofheinz (2003)
A mechanism of impaired mobility of oligodendrocyte progenitor cells by tenascin C through modification of wnt signaling
Y. Kakinuma (2004)
Quantitative control of active targeting of nanocarriers to tumor cells through optimization of folate ligand density.
Zhaomin Tang (2014)
Liposomes as targeted drug delivery systems in the treatment of breast cancer
G. Sharma (2006)
Application of nanostructured drug delivery systems in immunotherapy of cancer: a review
Nahideh Asadi (2017)
Development of Small RNA Delivery Systems for Lung Cancer Therapy
Y. Fujita (2015)
Long-Term Imatinib Treatment for Patients with Unresectable or Recurrent Gastrointestinal Stromal Tumors
K. Ogata (2018)
A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy.
Y. Tian (2014)
Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases.
M. Shibuya (2013)
Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer
N. Ferrara (2004)
Inorganic nanoparticles for cancer imaging and therapy.
Huang-Chiao Huang (2011)
Origin and function of tumor stroma fibroblasts.
Georgia Xouri (2010)
Role of therapeutic agents on repolarisation of tumour-associated macrophage to halt lung cancer progression
Hibah M Aldawsari (2019)
Nuclear and Fluorescent Labeled PD-1-Liposome-DOX-64Cu/IRDye800CW Allows Improved Breast Tumor Targeted Imaging and Therapy.
Y. Du (2017)
Confusing signals: Recent progress in CTLA-4 biology
L. Walker (2015)
Liposome-like Nanostructures for Drug Delivery.
W. Gao (2013)
AuNPs as an important inorganic nanoparticle applied in drug carrier systems
W. Li (2019)
Vitamin E Succinate-Grafted-Chitosan Oligosaccharide/RGD-Conjugated TPGS Mixed Micelles Loaded with Paclitaxel for U87MG Tumor Therapy.
Yanzuo Chen (2017)
This paper is referenced by
Preparation, physicochemical characterization and anti-fungal evaluation of Amphotericin B-Loaded PLGA-PEG-Galactosamine nanoparticles
Ghobad Mohammadi (2020)