Molecular Mechanisms and Emerging Therapeutic Targets of Triple-Negative Breast Cancer Metastasis

Ferlay, 2013, Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012, Eur J Cancer, 49, 1374, 10.1016/j.ejca.2012.12.027

Siegel, 2017, cancer statistics, 2017, CA Cancer J Clin, 67, 7, 10.3322/caac.21387

Polyak, 2011, Heterogeneity in breast cancer, J Clin Invest, 121, 3786, 10.1172/JCI60534

Carlson, 2009, Breast cancer. clinical practice guidelines in oncology, J Natl Compr Canc Netw, 7, 122, 10.6004/jnccn.2009.0012

Buzdar, 2009, Role of biologic therapy and chemotherapy in hormone receptor- and HER2-positive breast cancer, Ann Oncol, 20, 993, 10.1093/annonc/mdn739

Slamon, 2001, Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2, N Engl J Med, 344, 783, 10.1056/NEJM200103153441101

Anders, 2009, Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer, Clin Breast Cancer, 9, S73, 10.3816/CBC.2009.s.008

Hu, 2006, The molecular portraits of breast tumors are conserved across microarray platforms, BMC Genomics, 7, 96, 10.1186/1471-2164-7-96

2012, Comprehensive molecular portraits of human breast tumours, Nature, 490, 61, 10.1038/nature11412

De Abreu, 2013, The emerging role of the molecular diagnostics laboratory in breast cancer personalized medicine, Am J Pathol, 183, 1075, 10.1016/j.ajpath.2013.07.002

Perou, 2011, Molecular stratification of triple-negative breast cancers, Oncologist, 16, 61, 10.1634/theoncologist.2011-S1-61

Rakha, 2008, Are triple-negative and basal-like breast cancer synonymous?, Clin Cancer Res, 14, 618, 10.1158/1078-0432.CCR-07-1943

Rouzier, 2005, Breast cancer molecular subtypes respond differently to preoperative chemotherapy, Clin Cancer Res, 11, 5678, 10.1158/1078-0432.CCR-04-2421

Lehmann, 2016, Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection, PLoS One, 11, e0157368, 10.1371/journal.pone.0157368

Rangel, 2016, Developmental signaling pathways regulating mammary stem cells and contributing to the etiology of triple-negative breast cancer, Breast Cancer Res Treat, 156, 211, 10.1007/s10549-016-3746-7

2005, Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials, Lancet, 365, 1687, 10.1016/S0140-6736(05)66544-0

Ovcaricek, 2011, Triple negative breast cancer – prognostic factors and survival, Radiol Oncol, 45, 46, 10.2478/v10019-010-0054-4

Nguyen, 2007, Genetic determinants of cancer metastasis, Nat Rev Genet, 8, 341, 10.1038/nrg2101

Giancotti, 2013, Mechanisms governing metastatic dormancy and reactivation, Cell, 155, 750, 10.1016/j.cell.2013.10.029

Valastyan, 2011, Tumor metastasis: molecular insights and evolving paradigms, Cell, 147, 275, 10.1016/j.cell.2011.09.024

De Craene, 2013, Regulatory networks defining EMT during cancer initiation and progression, Nat Rev Cancer, 13, 97, 10.1038/nrc3447

Ferrari-Amorotti, 2014, Suppression of invasion and metastasis of triple-negative breast cancer lines by pharmacological or genetic inhibition of slug activity, Neoplasia, 16, 1047, 10.1016/j.neo.2014.10.006

Tran, 2014, Transient SNAIL1 expression is necessary for metastatic competence in breast cancer, Cancer Res, 74, 6330, 10.1158/0008-5472.CAN-14-0923

Yang, 2004, Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis, Cell, 117, 927, 10.1016/j.cell.2004.06.006

Choi, 2017, LOXL4 knockdown enhances tumor growth and lung metastasis through collagen-dependent extracellular matrix changes in triple-negative breast cancer, Oncotarget, 8, 11977, 10.18632/oncotarget.14450

Papageorgis, 2010, Smad signaling is required to maintain epigenetic silencing during breast cancer progression, Cancer Res, 70, 968, 10.1158/0008-5472.CAN-09-1872

Taylor, 2013, Upregulated WAVE3 expression is essential for TGF-beta-mediated EMT and metastasis of triple-negative breast cancer cells, Breast Cancer Res Treat, 142, 341, 10.1007/s10549-013-2753-1

Cheung, 2015, Role of epithelial-mesenchymal transition markers in triple-negative breast cancer, Breast Cancer Res Treat, 152, 489, 10.1007/s10549-015-3485-1

Jang, 2015, Expression of epithelial-mesenchymal transition-related markers in triple-negative breast cancer: ZEB1 as a potential biomarker for poor clinical outcome, Hum Pathol, 46, 1267, 10.1016/j.humpath.2015.05.010

Fischer, 2015, Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance, Nature, 527, 472, 10.1038/nature15748

Ye, 2017, Upholding a role for EMT in breast cancer metastasis, Nature, 547, E1, 10.1038/nature22816

Klein, 2009, Parallel progression of primary tumours and metastases, Nat Rev Cancer, 9, 302, 10.1038/nrc2627

Kang, 2003, A multigenic program mediating breast cancer metastasis to bone, Cancer Cell, 3, 537, 10.1016/S1535-6108(03)00132-6

Muller, 2001, Involvement of chemokine receptors in breast cancer metastasis, Nature, 410, 50, 10.1038/35065016

Liang, 2005, Silencing of CXCR4 blocks breast cancer metastasis, Cancer Res, 65, 967, 10.1158/0008-5472.967.65.3

Orimo, 2005, Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion, Cell, 121, 335, 10.1016/j.cell.2005.02.034

Masuda, 2015, ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling, Sci Rep, 5, 9170, 10.1038/srep09170

Rattanasinchai, 2017, MLK3 regulates FRA-1 and MMPs to drive invasion and transendothelial migration in triple-negative breast cancer cells, Oncogenesis, 6, e345, 10.1038/oncsis.2017.44

Chen, 2012, MLK3 regulates paxillin phosphorylation in chemokine-mediated breast cancer cell migration and invasion to drive metastasis, Cancer Res, 72, 4130, 10.1158/0008-5472.CAN-12-0655

Adorno, 2009, A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis, Cell, 137, 87, 10.1016/j.cell.2009.01.039

Papageorgis, 2015, Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung metastasis, Breast Cancer Res, 17, 98, 10.1186/s13058-015-0607-y

Su, 2010, TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs, Nature, 467, 986, 10.1038/nature09459

Chen, 2012, LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker, Nat Med, 18, 1511, 10.1038/nm.2940

Wang, 2015, FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer, Breast Cancer Res, 17, 30, 10.1186/s13058-015-0531-1

Jiang, 2016, SSBP1 suppresses TGFbeta-driven epithelial-to-mesenchymal transition and metastasis in triple-negative breast cancer by regulating mitochondrial retrograde signaling, Cancer Res, 76, 952, 10.1158/0008-5472.CAN-15-1630

Jiang, 2015, Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-beta/SMAD signaling, Oncotarget, 6, 16352, 10.18632/oncotarget.3877

Jin, 2012, TIEG1 inhibits breast cancer invasion and metastasis by inhibition of epidermal growth factor receptor (EGFR) transcription and the EGFR signaling pathway, Mol Cell Biol, 32, 50, 10.1128/MCB.06152-11

Douma, 2004, Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB, Nature, 430, 1034, 10.1038/nature02765

Tsai, 2017, Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer, PLoS One, 12, e0178173, 10.1371/journal.pone.0178173

Wenzel, 2010, Inhibition of metastasis in a murine 4T1 breast cancer model by liposomes preventing tumor cell-platelet interactions, Clin Exp Metastasis, 27, 25, 10.1007/s10585-009-9299-y

Gay, 2011, Contribution of platelets to tumour metastasis, Nat Rev Cancer, 11, 123, 10.1038/nrc3004

Padua, 2008, TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4, Cell, 133, 66, 10.1016/j.cell.2008.01.046

DeJong, 2007, Reactive oxygen species detoxification by catalase is a major determinant of fecundity in the mosquito Anopheles gambiae, Proc Natl Acad Sci U S A, 104, 2121, 10.1073/pnas.0608407104

Wright, 2017, CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation, Proc Natl Acad Sci U S A, 114, E6556, 10.1073/pnas.1703791114

Larkins, 2006, Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression, BMC Cancer, 6, 181, 10.1186/1471-2407-6-181

Singh, 2007, COX-2 involvement in breast cancer metastasis to bone, Oncogene, 26, 3789, 10.1038/sj.onc.1210154

Tian, 2017, Cyclooxygenase-2 regulates TGFbeta-induced cancer stemness in triple-negative breast cancer, Sci Rep, 7, 40258, 10.1038/srep40258

Park, 2007, NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF, Nat Med, 13, 62, 10.1038/nm1519

Acharyya, 2012, A CXCL1 paracrine network links cancer chemoresistance and metastasis, Cell, 150, 165, 10.1016/j.cell.2012.04.042

Minn, 2005, Genes that mediate breast cancer metastasis to lung, Nature, 436, 518, 10.1038/nature03799

Harris, 2012, Increased vascularity and spontaneous metastasis of breast cancer by hedgehog signaling mediated upregulation of cyr61, Oncogene, 31, 3370, 10.1038/onc.2011.496

Dey, 2010, Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis, Cancer Res, 70, 4151, 10.1158/0008-5472.CAN-09-4479

Chen, 2010, Migrastatin analogues target fascin to block tumour metastasis, Nature, 464, 1062, 10.1038/nature08978

Al-Alwan, 2011, Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules, PLoS One, 6, e27339, 10.1371/journal.pone.0027339

Gupta, 2007, ID genes mediate tumor reinitiation during breast cancer lung metastasis, Proc Natl Acad Sci U S A, 104, 19506, 10.1073/pnas.0709185104

Fong, 2003, Id-1 as a molecular target in therapy for breast cancer cell invasion and metastasis, Proc Natl Acad Sci U S A, 100, 13543, 10.1073/pnas.2230238100

Tominaga, 2017, Addiction to the IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells, Oncogene, 36, 1276, 10.1038/onc.2016.293

Wee, 2015, IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel, Nat Commun, 6, 8746, 10.1038/ncomms9746

Dong, 2017, Tumor LDH-A expression and serum LDH status are two metabolic predictors for triple negative breast cancer brain metastasis, Sci Rep, 7, 6069, 10.1038/s41598-017-06378-7

Vergara, 2013, Comparative proteome profiling of breast tumor cell lines by gel electrophoresis and mass spectrometry reveals an epithelial mesenchymal transition associated protein signature, Mol Biosyst, 9, 1127, 10.1039/c2mb25401h

Boucharaba, 2004, Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer, J Clin Invest, 114, 1714, 10.1172/JCI22123

Okita, 2017, The transcription factor MAFK induces EMT and malignant progression of triple-negative breast cancer cells through its target GPNMB, Sci Signal, 10, eaak9397, 10.1126/scisignal.aak9397

Blomme, 2017, Myoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer, Oncogene, 36, 2116, 10.1038/onc.2016.369

Granados-Principal, 2015, Inhibition of iNOS as a novel effective targeted therapy against triple-negative breast cancer, Breast Cancer Res, 17, 25, 10.1186/s13058-015-0527-x

Azzam, 2013, Triple negative breast cancer initiating cell subsets differ in functional and molecular characteristics and in gamma-secretase inhibitor drug responses, EMBO Mol Med, 5, 1502, 10.1002/emmm.201302558

Weber, 2015, Osteopontin mediates an MZF1-TGF-beta1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer, Oncogene, 34, 4821, 10.1038/onc.2014.410

Mi, 2009, RNA aptamer blockade of osteopontin inhibits growth and metastasis of MDA-MB231 breast cancer cells, Mol Ther, 17, 153, 10.1038/mt.2008.235

Chen, 2016, Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer, Nature, 533, 493, 10.1038/nature18268

Paul, 2014, PKClambda/iota signaling promotes triple-negative breast cancer growth and metastasis, Cell Death Differ, 21, 1469, 10.1038/cdd.2014.62

Ponente, 2017, PML promotes metastasis of triple-negative breast cancer through transcriptional regulation of HIF1A target genes, JCI Insight, 2, e87380, 10.1172/jci.insight.87380

Malanchi, 2011, Interactions between cancer stem cells and their niche govern metastatic colonization, Nature, 481, 85, 10.1038/nature10694

Lambert, 2016, Tumor cell-derived periostin regulates cytokines that maintain breast cancer stem cells, Mol Cancer Res, 14, 103, 10.1158/1541-7786.MCR-15-0079

Yin, 1999, TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development, J Clin Invest, 103, 197, 10.1172/JCI3523

Taipaleenmaki, 2016, Antagonizing miR-218-5p attenuates Wnt signaling and reduces metastatic bone disease of triple negative breast cancer cells, Oncotarget, 7, 79032, 10.18632/oncotarget.12593

Kamalati, 2000, Expression of the BRK tyrosine kinase in mammary epithelial cells enhances the coupling of EGF signalling to PI 3-kinase and Akt, via erbB3 phosphorylation, Oncogene, 19, 5471, 10.1038/sj.onc.1203931

Ito, 2016, PTK6 inhibition suppresses metastases of triple-negative breast cancer via SNAIL-dependent E-cadherin regulation, Cancer Res, 76, 4406, 10.1158/0008-5472.CAN-15-3445

Wiegmans, 2014, Rad51 supports triple negative breast cancer metastasis, Oncotarget, 5, 3261, 10.18632/oncotarget.1923

Nasser, 2015, RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment, Cancer Res, 75, 974, 10.1158/0008-5472.CAN-14-2161

Jones, 2006, Regulation of cancer cell migration and bone metastasis by RANKL, Nature, 440, 692, 10.1038/nature04524

Nasser, 2012, S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways, Cancer Res, 72, 604, 10.1158/0008-5472.CAN-11-0669

Valiente, 2014, Serpins promote cancer cell survival and vascular co-option in brain metastasis, Cell, 156, 1002, 10.1016/j.cell.2014.01.040

Savagner, 1997, The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition, J Cell Biol, 137, 1403, 10.1083/jcb.137.6.1403

Kim, 2014, Slug promotes survival during metastasis through suppression of puma-mediated apoptosis, Cancer Res, 74, 3695, 10.1158/0008-5472.CAN-13-2591

Dhasarathy, 2011, The transcription factors snail and slug activate the transforming growth factor-beta signaling pathway in breast cancer, PLoS One, 6, e26514, 10.1371/journal.pone.0026514

Cano, 2000, The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression, Nat Cell Biol, 2, 76, 10.1038/35000025

Kim, 2016, EGF induces epithelial-mesenchymal transition through phospho-Smad2/3-Snail signaling pathway in breast cancer cells, Oncotarget, 7, 85021, 10.18632/oncotarget.13116

He, 2016, Suppression of Spry1 inhibits triple-negative breast cancer malignancy by decreasing EGF/EGFR mediated mesenchymal phenotype, Sci Rep, 6, 23216, 10.1038/srep23216

Bos, 2009, Genes that mediate breast cancer metastasis to the brain, Nature, 459, 1005, 10.1038/nature08021

Tang, 2003, TGF-beta switches from tumor suppressor to prometastatic factor in a model of breast cancer progression, J Clin Invest, 112, 1116, 10.1172/JCI18899

Kang, 2005, Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway, Proc Natl Acad Sci U S A, 102, 13909, 10.1073/pnas.0506517102

Oskarsson, 2011, Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs, Nat Med, 17, 867, 10.1038/nm.2379

Howe, 2003, Twist is up-regulated in response to Wnt1 and inhibits mouse mammary cell differentiation, Cancer Res, 63, 1906

Lu, 2011, VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging alpha4beta1-positive osteoclast progenitors, Cancer Cell, 20, 701, 10.1016/j.ccr.2011.11.002

Chen, 2011, Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs, Cancer Cell, 20, 538, 10.1016/j.ccr.2011.08.025

Jang, 2015, Blockade of Wnt/beta-catenin signaling suppresses breast cancer metastasis by inhibiting CSC-like phenotype, Sci Rep, 5, 12465, 10.1038/srep12465

Dey, 2013, Wnt signaling in triple negative breast cancer is associated with metastasis, BMC Cancer, 13, 537, 10.1186/1471-2407-13-537

Geyer, 2011, beta-Catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation, Mod Pathol, 24, 209, 10.1038/modpathol.2010.205

Di Franco, 2016, DeltaNp63 drives metastasis in breast cancer cells via PI3K/CD44v6 axis, Oncotarget, 7, 54157, 10.18632/oncotarget.11022

Ozturk, 2016, SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis, Proc Natl Acad Sci U S A, 113, 638, 10.1073/pnas.1514663113

Montagner, 2012, SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors, Nature, 487, 380, 10.1038/nature11207

Shen, 2015, Metabolic reprogramming in triple-negative breast cancer through Myc suppression of TXNIP, Proc Natl Acad Sci U S A, 112, 5425, 10.1073/pnas.1501555112

Chen, 2015, MiR-373 drives the epithelial-to-mesenchymal transition and metastasis via the miR-373-TXNIP-HIF1alpha-TWIST signaling axis in breast cancer, Oncotarget, 6, 32701, 10.18632/oncotarget.4702

Gunasinghe, 2012, Mesenchymal-epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer, Cancer Metastasis Rev, 31, 469, 10.1007/s10555-012-9377-5

Gregory, 2008, The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1, Nat Cell Biol, 10, 593, 10.1038/ncb1722

Dykxhoorn, 2009, miR-200 enhances mouse breast cancer cell colonization to form distant metastases, PLoS One, 4, e7181, 10.1371/journal.pone.0007181

Mundy, 2002, Metastasis to bone: causes, consequences and therapeutic opportunities, Nat Rev Cancer, 2, 584, 10.1038/nrc867

De Cock, 2016, Inflammation triggers Zeb1-dependent escape from tumor latency, Cancer Res, 76, 6778, 10.1158/0008-5472.CAN-16-0608

Wong, 2011, Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation, Proc Natl Acad Sci U S A, 108, 16369, 10.1073/pnas.1113483108

Bosch, 2010, Triple-negative breast cancer: molecular features, pathogenesis, treatment and current lines of research, Cancer Treat Rev, 36, 206, 10.1016/j.ctrv.2009.12.002

Okuma, 2017, BRCA Gene Mutations and Poly(ADP-Ribose) Polymerase Inhibitors in Triple-Negative Breast Cancer, Adv Exp Med Biol, 1026, 271, 10.1007/978-981-10-6020-5_13

Tutt, 2010, Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial, Lancet, 376, 235, 10.1016/S0140-6736(10)60892-6

Dent, 2013, Phase I trial of the oral PARP inhibitor olaparib in combination with paclitaxel for first- or second-line treatment of patients with metastatic triple-negative breast cancer, Breast Cancer Res, 15, R88, 10.1186/bcr3484

Gucalp, 2013, Cancer Research: Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer, Clin Cancer Res, 19, 5505, 10.1158/1078-0432.CCR-12-3327

Gelmon, 2012, Targeting triple-negative breast cancer: optimising therapeutic outcomes, Ann Oncol, 23, 2223, 10.1093/annonc/mds067

Locatelli, 2017, Phase I study of the gamma secretase inhibitor PF-03084014 in combination with docetaxel in patients with advanced triple-negative breast cancer, Oncotarget, 8, 2320, 10.18632/oncotarget.13727

Chen, 2017, Elements of cancer immunity and the cancer-immune set point, Nature, 541, 321, 10.1038/nature21349

Zou, 2016, PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations, Sci Transl Med, 8, 328rv4, 10.1126/scitranslmed.aad7118

Bianchini, 2016, Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease, Nat Rev Clin Oncol, 13, 674, 10.1038/nrclinonc.2016.66

Walker, 2001, The complexities of breast cancer desmoplasia, Breast Cancer Res, 3, 143, 10.1186/bcr287

Jain, 2014, The role of mechanical forces in tumor growth and therapy, Annu Rev Biomed Eng, 16, 321, 10.1146/annurev-bioeng-071813-105259

Gkretsi, 2015, Remodeling components of the tumor microenvironment to enhance cancer therapy, Front Oncol, 5, 214, 10.3389/fonc.2015.00214

Takai, 2016, Targeting the cancer-associated fibroblasts as a treatment in triple-negative breast cancer, Oncotarget, 7, 82889, 10.18632/oncotarget.12658

Polydorou, 2017, Pirfenidone normalizes the tumor microenvironment to improve chemotherapy, Oncotarget, 8, 24506, 10.18632/oncotarget.15534

Papageorgis, 2017, Tranilast-induced stress alleviation in solid tumors improves the efficacy of chemo- and nanotherapeutics in a size-independent manner, Sci Rep, 7, 46140, 10.1038/srep46140

Chauhan, 2013, Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels, Nat Commun, 4, 2516, 10.1038/ncomms3516

Diop-Frimpong, 2011, Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors, Proc Natl Acad Sci U S A, 108, 2909, 10.1073/pnas.1018892108