Improving therapeutic resistance: beginning with targeting the tumor microenvironment

References

• Gould CM, Courtneidge SA. Regulation of invadopodia by the tumor microenvironment. Cell Adh Migr. 2014;8(3):226–235.
   PubMed Web of Science ®Google Scholar
• Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989;8(2):98–101.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA, Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.
   Google Scholar
• Räsänen K, Vaheri A. Activation of fibroblasts in cancer stroma. Exp Cell Res. 2010;316(17):2713–2722.
   PubMed Web of Science ®Google Scholar
• Anderberg C, Pietras K. On the origin of cancer-associated fibroblasts. Cell Cycle. 2009;8(10):1461–1462.
   PubMed Web of Science ®Google Scholar
• Tao L, Huang G, Song H, et al. Cancer associated fibroblasts: an essential role in the tumor microenvironment. Oncol Lett. 2017;14(3):2611–2620.
   PubMed Web of Science ®Google Scholar
• Öhlund D, Handly-Santana A, Biffi G, et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med. 2017;214(3):579–596.
   PubMed Web of Science ®Google Scholar
• Izumi D, Ishimoto T, Miyake K, et al. CXCL12/CXCR4 activation by cancer-associated fibroblasts promotes integrin β1 clustering and invasiveness in gastric cancer. Int J Cancer. 2016;138(5):1207–1219.
   PubMed Web of Science ®Google Scholar
• Das M, Law S. Role of tumor microenvironment in cancer stem cell chemoresistance and recurrence. Int J Biochem Cell Biol. 2018;103:115–124.
   PubMed Web of Science ®Google Scholar
• Nagasaki T, Hara M, Nakanishi H, et al. Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour-stroma interaction. Br J Cancer. 2014;110(2):469–478.
   PubMed Web of Science ®Google Scholar
• Zhou W, Xu G, Wang Y, et al. Oxidative stress induced autophagy in cancer associated fibroblast enhances proliferation and metabolism of colorectal cancer cells. Cell Cycle. 2017;16(1):73–81.
   PubMed Web of Science ®Google Scholar
• Sanford-Crane H, Abrego J, Sherman MH. Fibroblasts as modulators of local and systemic cancer metabolism. Cancers (Basel). 2019;11(5):619.
   Web of Science ®Google Scholar
• Butler JM, Kobayashi H, Rafii S. Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors. Nat Rev Cancer. 2010;10(2):138–146.
   PubMed Web of Science ®Google Scholar
• Akiyama K, Ohga N, Hida Y, et al. Tumor endothelial cells acquire drug resistance by MDR1 up-regulation via VEGF signaling in tumor microenvironment. Am J Pathol. 2012;180(3):1283–1293.
   PubMed Web of Science ®Google Scholar
• Hida K, Maishi N, Annan DA. Contribution of tumor endothelial cells in cancer progression. Int J Mol Sci. 2018;19(5):1272.
   PubMed Web of Science ®Google Scholar
• Ribeiro Franco PI, Rodrigues AP, de Menezes LB, et al. Tumor microenvironment components: allies of cancer progression. Pathol Res Pract. 2020;216(1):152729.
   PubMed Web of Science ®Google Scholar
• Abbasi MM, Mehdipour M, Monfaredan A, et al. Hesa-A down-regulates erb/b2 oncogene expression and improves outcome of oral carcinoma in a rat model. Asian Pac J Cancer Prev. 2015;16(16):6947–6951.
   PubMedGoogle Scholar
• Birbrair A. Pericyte biology: development, homeostasis, and disease. Adv Exp Med Biol. 2018;1109:1–3.
   PubMed Web of Science ®Google Scholar
• Chen Z, Xu XH, Hu J. Role of pericytes in angiogenesis: focus on cancer angiogenesis and anti-angiogenic therapy. Neoplasma. 2016;63(2):173–182.
   PubMed Web of Science ®Google Scholar
• Fridman WH, Pages F, Sautes-Fridman C, et al. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298–306.
   PubMed Web of Science ®Google Scholar
• Jain RK. Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell. 2014;26(5):605–622.
   PubMed Web of Science ®Google Scholar
• Cook J, Hagemann T. Tumour-associated macrophages and cancer. Curr Opin Pharmacol. 2013;13(4):595–601.
   PubMed Web of Science ®Google Scholar
• Sica A, Larghi P, Mancino A, et al. Macrophage polarization in tumour progression. Semin Cancer Biol. 2008;18(5):349–355.
   PubMed Web of Science ®Google Scholar
• Mantovani A, Marchesi F, Malesci A, et al. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017;14(7):399–416.
   PubMed Web of Science ®Google Scholar
• Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942–949.
   PubMed Web of Science ®Google Scholar
• Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889–896.
   PubMed Web of Science ®Google Scholar
• Jeong H, Hwang I, Kang SH, et al. Tumor-associated macrophages as potential prognostic biomarkers of invasive breast cancer. J Breast Cancer. 2019;22(1):38–51.
   PubMed Web of Science ®Google Scholar
• Yu M, Guan R, Hong W, et al. Prognostic value of tumor-associated macrophages in pancreatic cancer: a meta-analysis. Cancer Manag Res. 2019;11:4041–4058.
   PubMed Web of Science ®Google Scholar
• Rakaee M, Busund LR, Jamaly S, et al. Prognostic value of macrophage phenotypes in resectable non-small cell lung cancer assessed by multiplex immunohistochemistry. Neoplasia. 2019;21(3):282–293.
   PubMed Web of Science ®Google Scholar
• Germano G, Frapolli R, Belgiovine C, et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell. 2013;23(2):249–262.
   PubMed Web of Science ®Google Scholar
• Kumar V, Cheng P, Condamine T, et al. CD45 phosphatase inhibits STAT3 transcription factor activity in myeloid cells and promotes tumor-associated macrophage differentiation. Immunity. 2016;44(2):303–315.
   PubMed Web of Science ®Google Scholar
• Acharyya S, Oskarsson T, Vanharanta S, et al. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell. 2012;150(1):165–178.
   PubMed Web of Science ®Google Scholar
• Ostrand-Rosenberg S. Immune surveillance: a balance between protumor and antitumor immunity. Curr Opin Genet Dev. 2008;18(1):11–18.
   PubMed Web of Science ®Google Scholar
• Zhang X, Xiang J. Remodeling the microenvironment before occurrence and metastasis of cancer. Int J Biol Sci. 2019;15(1):105–113.
   PubMed Web of Science ®Google Scholar
• von Boehmer H, Daniel C. Therapeutic opportunities for manipulating T(reg) cells in autoimmunity and cancer. Nat Rev Drug Discov. 2013;12(1):51–63.
   PubMed Web of Science ®Google Scholar
• Kyurkchiev D, Bochev I, Ivanova-Todorova E, et al. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells. 2014;6(5):552–570.
   PubMedGoogle Scholar
• Roussos ET, Condeelis JS, Patsialou A. Chemotaxis in cancer. Nat Rev Cancer. 2011;11(8):573–587.
   PubMed Web of Science ®Google Scholar
• Wyckoff J, Wang W, Lin EY, et al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 2004;64(19):7022–7029.
   PubMed Web of Science ®Google Scholar
• Muller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410(6824):50–56.
   PubMed Web of Science ®Google Scholar
• Biragyn A, Longo DL. Neoplastic "black ops": cancer's subversive tactics in overcoming host defenses. Semin Cancer Biol. 2012;22(1):50–59.
   PubMed Web of Science ®Google Scholar
• Walker C, Mojares E, Del Río Hernández A. Role of extracellular matrix in development and cancer progression. Int J Mol Sci. 2018;19(10):3028.
   Web of Science ®Google Scholar
• Lu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol. 2012;196(4):395–406.
   PubMed Web of Science ®Google Scholar
• Benias PC, Wells RG, Sackey-Aboagye B, et al. Structure and distribution of an unrecognized interstitium in human tissues. Sci Rep. 2018;8(1):4947.
   PubMedGoogle Scholar
• Sleeboom JJF, Eslami Amirabadi H, Nair P. Metastasis in context: modeling the tumor microenvironment with cancer-on-a-chip approaches. 2018;11(3):dmm033100.
   Google Scholar
• Friedl P, Alexander S. Cancer invasion and the microenvironment: plasticity and reciprocity. Cell. 2011;147(5):992–1009.
   PubMed Web of Science ®Google Scholar
• Jena MK, Janjanam J. Role of extracellular matrix in breast cancer development: a brief update. F1000Res. 2018;7:274.
   PubMedGoogle Scholar
• Sailaja BS, He XC, Li L. The regulatory niche of intestinal stem cells. J Physiol. 2016;594(17):4827–4836.
   PubMed Web of Science ®Google Scholar
• Xu S, Xu H, Wang W, et al. The role of collagen in cancer: from bench to bedside. J Transl Med. 2019;17(1):309.
   PubMed Web of Science ®Google Scholar
• Whatcott CJ, Han H, Posner RG, et al. Targeting the tumor microenvironment in cancer: why hyaluronidase deserves a second look. Cancer Discov. 2011;1(4):291–296.
   PubMed Web of Science ®Google Scholar
• Sun Y. Tumor microenvironment and cancer therapy resistance. Cancer Lett. 2016;380(1):205–215.
   PubMed Web of Science ®Google Scholar
• Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473(7347):298–307.
   PubMed Web of Science ®Google Scholar
• Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21(3):309–322.
   PubMed Web of Science ®Google Scholar
• Schoppmann SF, Birner P, Stöckl J, et al. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol. 2002;161(3):947–956.
   PubMed Web of Science ®Google Scholar
• Boelens MC, Wu TJ, Nabet BY, et al. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell. 2014;159(3):499–513.
   PubMed Web of Science ®Google Scholar
• Schageman J, Zeringer E, Li M, et al. The complete exosome workflow solution: from isolation to characterization of RNA cargo. Biomed Res Int. 2013;2013:253957.
   PubMed Web of Science ®Google Scholar
• Costa-Silva B, Aiello NM, Ocean AJ, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015;17(6):816–826.
   PubMed Web of Science ®Google Scholar
• Gowda R, Robertson BM, Iyer S, et al. The role of exosomes in metastasis and progression of melanoma. Cancer Treat Rev. 2020;85:101975.
   PubMed Web of Science ®Google Scholar
• Mu W, Rana S, Zoller M. Host matrix modulation by tumor exosomes promotes motility and invasiveness. Neoplasia. 2013;15(8):875–887.
   PubMed Web of Science ®Google Scholar
• Baghban R, Roshangar L, Jahanban-Esfahlan R, et al. Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal. 2020;18(1):59.
   PubMed Web of Science ®Google Scholar
• Liu Y, Cao X. Organotropic metastasis: role of tumor exosomes. Cell Res. 2016;26(2):149–150.
   PubMed Web of Science ®Google Scholar
• Fong MY, Zhou W, Liu L, et al. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol. 2015;17(2):183–194.
   PubMed Web of Science ®Google Scholar
• Fukumura D, Jain RK. Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization. Microvasc Res. 2007;74(2–3):72–84.
   PubMed Web of Science ®Google Scholar
• Semenza GL. Cancer-stromal cell interactions mediated by hypoxia-inducible factors promote angiogenesis, lymphangiogenesis, and metastasis. Oncogene. 2013;32(35):4057–4063.
   PubMed Web of Science ®Google Scholar
• Semenza LG. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721–732.
   PubMed Web of Science ®Google Scholar
• Diaz B, Yuen A, Iizuka S, et al. Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia. J Cell Biol. 2013;201(2):279–292.
   PubMed Web of Science ®Google Scholar
• Pastorek J, Pastorekova S. Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: from biology to clinical use. Semin Cancer Biol. 2015;31:52–64.
   PubMed Web of Science ®Google Scholar
• Zhang W, Zhou X, Yao Q, et al. HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular cells. Am J Physiol Renal Physiol. 2017;313(4):F906–f13.
   PubMed Web of Science ®Google Scholar
• Noman MZ, Desantis G, Janji B, et al. PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014;211(5):781–790.
   PubMed Web of Science ®Google Scholar
• Greijer AE, van der Wall E. The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. J Clin Pathol. 2004;57(10):1009–1014.
   PubMed Web of Science ®Google Scholar
• Achison M, Hupp TR. Hypoxia attenuates the p53 response to cellular damage. Oncogene. 2003;22(22):3431–3440.
   PubMed Web of Science ®Google Scholar
• Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8(6):519–530.
   PubMedGoogle Scholar
• Ni WD, Yang ZT, Cui CA, et al. Tenascin-C is a potential cancer-associated fibroblasts marker and predicts poor prognosis in prostate cancer. Biochem Biophys Res Commun. 2017;486(3):607–612.
   PubMed Web of Science ®Google Scholar
• Whitaker-Menezes D, Martinez-Outschoorn UE, Lin Z, et al. Evidence for a stromal-epithelial "lactate shuttle" in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts. Cell Cycle. 2011;10(11):1772–1783.
   PubMed Web of Science ®Google Scholar
• Benny S, Mishra R, Manojkumar MK, et al. From Warburg effect to reverse Warburg effect; the new horizons of anti-cancer therapy. Med Hypotheses. 2020;144:110216.
   PubMed Web of Science ®Google Scholar
• Xu L, Fukumura D, Jain RK. Acidic extracellular pH induces vascular endothelial growth factor (VEGF) in human glioblastoma cells via ERK1/2 MAPK signaling pathway: mechanism of low pH-induced VEGF. J Biol Chem. 2002;277(13):11368–11374.
   PubMed Web of Science ®Google Scholar
• Ban JJ, Lee M, Im W, et al. Low pH increases the yield of exosome isolation. Biochem Biophys Res Commun. 2015;461(1):76–79.
   PubMed Web of Science ®Google Scholar
• Sun Y. Translational horizons in the tumor microenvironment: harnessing breakthroughs and targeting cures. Med Res Rev. 2015;35(2):408–436.
   PubMed Web of Science ®Google Scholar
• Chen F, Zhuang X, Lin L, et al. New horizons in tumor microenvironment biology: challenges and opportunities. BMC Med. 2015;13:45.
   PubMed Web of Science ®Google Scholar
• Manegold C, Vansteenkiste J, Cardenal F, et al. Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer. Invest New Drugs. 2013;31(1):175–182.
   PubMed Web of Science ®Google Scholar
• Cirkel GA, Kerklaan BM, Vanhoutte F, et al. A dose escalating phase I study of GLPG0187, a broad spectrum integrin receptor antagonist, in adult patients with progressive high-grade glioma and other advanced solid malignancies. Invest New Drugs. 2016;34(2):184–192.
   PubMed Web of Science ®Google Scholar
• Silva VL, Kaassis A, Dehsorkhi A, et al. Enhanced selectivity, cellular uptake, and in vitro activity of an intrinsically fluorescent copper-tirapazamine nanocomplex for hypoxia targeted therapy in prostate cancer. Biomater Sci. 2020;8(9):2420–2433.
   PubMed Web of Science ®Google Scholar
• Yang S, Tang Z, Hu C, et al. Selectively potentiating hypoxia levels by combretastatin A4 nanomedicine: toward highly enhanced Hypoxia-Activated prodrug tirapazamine therapy for metastatic tumors. Adv Mater. 2019;31(11):e1805955.
   PubMed Web of Science ®Google Scholar
• Spiegelberg L, van Hoof SJ, Biemans R, et al. Evofosfamide sensitizes esophageal carcinomas to radiation without increasing normal tissue toxicity. Radiother Oncol. 2019;141:247–255.
   PubMed Web of Science ®Google Scholar
• Carroll CE, Liang Y, Benakanakere I, et al. The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development. Int J Oncol. 2013;42(1):179–187.
   PubMed Web of Science ®Google Scholar
• Kessler J, Hahnel A, Wichmann H, et al. HIF-1α inhibition by siRNA or chetomin in human malignant glioma cells: effects on hypoxic radioresistance and monitoring via CA9 expression. BMC Cancer. 2010;10:605.
   PubMed Web of Science ®Google Scholar
• Wang LM, Zhang LL, Wang LW, Zhu L, Ma XX. Influence of miR-199a on rats with non-small cell lung cancer via regulating the HIF-1alpha/VEGF signaling pathway. Eur Rev Med Pharmacol Sci. 2019;23:10363–10369.
   PubMedGoogle Scholar
• Guan L, Zou Q, Liu Q, et al. HSP90 inhibitor ganetespib (STA-9090) inhibits tumor growth in c-Myc-Dependent esophageal squamous cell carcinoma. Onco Targets Ther. 2020;13:2997–3011.
   PubMed Web of Science ®Google Scholar
• Courtney KD, Infante JR, Lam ET, et al. Phase I dose-escalation trial of PT2385, a first-in-class hypoxia-inducible factor-2α antagonist in patients with previously treated advanced clear cell renal cell carcinoma. J Clin Oncol. 2018;36(9):867–874.
   PubMed Web of Science ®Google Scholar
• Zai W, Chen W, Han Y, et al. Targeting PARP and autophagy evoked synergistic lethality in hepatocellular carcinoma. Carcinogenesis. 2020;41(3):345–357.
   PubMed Web of Science ®Google Scholar
• Barnard RA, Wittenburg LA, Amaravadi RK, et al. Phase I clinical trial and pharmacodynamic evaluation of combination hydroxychloroquine and doxorubicin treatment in pet dogs treated for spontaneously occurring lymphoma. Autophagy. 2014;10(8):1415–1425.
   PubMed Web of Science ®Google Scholar
• Lee YJ, Won AJ, Lee J, et al. Molecular mechanism of SAHA on regulation of autophagic cell death in tamoxifen-resistant MCF-7 breast cancer cells. Int J Med Sci. 2012;9(10):881–893.
   PubMed Web of Science ®Google Scholar
• Li JR, Cheng CL, Yang CR, et al. Dual inhibitor of phosphoinositide 3-kinase/mammalian target of rapamycin NVP-BEZ235 effectively inhibits cisplatin-resistant urothelial cancer cell growth through autophagic flux. Toxicol Lett. 2013;220(3):267–276.
   PubMed Web of Science ®Google Scholar
• Vendetti FP, Karukonda P, Clump DA, et al. ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity following radiation. J Clin Invest. 2018;128(9):3926–3940.
   PubMed Web of Science ®Google Scholar
• Wallez Y, Dunlop CR, Johnson TI, et al. The ATR inhibitor AZD6738 synergizes with gemcitabine in vitro and in vivo to induce pancreatic ductal adenocarcinoma regression. Mol Cancer Ther. 2018;17(8):1670–1682.
   PubMed Web of Science ®Google Scholar
• Riches LC, Trinidad AG, Hughes G, et al. Pharmacology of the ATM inhibitor AZD0156: potentiation of irradiation and olaparib responses preclinically. 2020;19:13–25.
   Google Scholar
• Fok JHL, Ramos-Montoya A, Vazquez-Chantada M, et al. AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun. 2019;10(1):5065.
   PubMed Web of Science ®Google Scholar
• Timme CR, Rath BH, O'Neill JW, et al. The DNA-PK inhibitor VX-984 enhances the radiosensitivity of glioblastoma cells grown in vitro and as orthotopic xenografts. Mol Cancer Ther. 2018;17(6):1207–1216.
   PubMed Web of Science ®Google Scholar
• Taverna P, Hwang HS, Schupp JE, et al. Inhibition of base excision repair potentiates iododeoxyuridine-induced cytotoxicity and radiosensitization. Cancer Res. 2003;63(4):838–846.
   PubMed Web of Science ®Google Scholar
• Rashidi A, Uy GL. Targeting the microenvironment in acute myeloid leukemia. Curr Hematol Malig Rep. 2015;10(2):126–131.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Hou X, Evans BJ, et al. LY2157299 monohydrate, a TGF-βR1 inhibitor, suppresses tumor growth and ascites development in ovarian cancer. Cancers (Basel). 2018;10(8):260.
   Web of Science ®Google Scholar
• DeNardo DG, Brennan DJ, Rexhepaj E, et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 2011;1(1):54–67.
   PubMed Web of Science ®Google Scholar
• Li X, Yao W, Yuan Y, et al. Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma. Gut. 2017;66(1):157–167.
   PubMed Web of Science ®Google Scholar
• Nywening TM, Wang-Gillam A, Sanford DE, et al. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-Centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol. 2016;17(5):651–662.
   PubMed Web of Science ®Google Scholar
• Cassetta L, Kitamura T. Targeting tumor-associated macrophages as a potential strategy to enhance the response to immune checkpoint inhibitors. Front Cell Dev Biol. 2018;6:38.
   PubMed Web of Science ®Google Scholar
• Pallasch CP, Leskov I, Braun CJ, et al. Sensitizing protective tumor microenvironments to antibody-mediated therapy. Cell. 2014;156(3):590–602.
   PubMed Web of Science ®Google Scholar
• Nishida-Aoki N, Tominaga N, Takeshita F, et al. Disruption of circulating extracellular vesicles as a novel therapeutic strategy against cancer metastasis. Mol Ther. 2017;25(1):181–191.
   PubMed Web of Science ®Google Scholar
• Gomari H, Forouzandeh Moghadam M, Soleimani M. Targeted cancer therapy using engineered exosome as a natural drug delivery vehicle. Onco Targets Ther. 2018;11:5753–5762.
   PubMed Web of Science ®Google Scholar
• Pascucci L, Coccè V, Bonomi A, et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J Control Release. 2014;192:262–270.
   PubMed Web of Science ®Google Scholar
• Lo A, Wang LS, Scholler J, et al. Tumor-promoting desmoplasia is disrupted by depleting FAP-Expressing stromal cells. Cancer Res. 2015;75(14):2800–2810.
   PubMed Web of Science ®Google Scholar
• Ishii N, Araki K, Yokobori T, et al. Conophylline suppresses pancreatic cancer desmoplasia and cancer-promoting cytokines produced by cancer-associated fibroblasts. Cancer Sci. 2019;110(1):334–344.
   PubMed Web of Science ®Google Scholar
• Miao L, Liu Q, Lin CM, et al. Targeting tumor-associated fibroblasts for therapeutic delivery in desmoplastic tumors. Cancer Res. 2017;77(3):719–731.
   PubMed Web of Science ®Google Scholar
• Li X, Huang F, Xu X, et al. Polyclonal rabbit anti-cancer-associated fibroblasts globulins induce cancer cells apoptosis and inhibit tumor growth. Int J Biol Sci. 2018;14(12):1621–1629.
   PubMed Web of Science ®Google Scholar
• Chen B, Wang Z, Sun J, et al. A tenascin C targeted nanoliposome with navitoclax for specifically eradicating of cancer-associated fibroblasts. Nanomedicine. 2016;12(1):131–141.
   PubMed Web of Science ®Google Scholar
• Bai ZG, Zhang ZT. A systematic review and meta-analysis on the effect of angiogenesis blockade for the treatment of gastric cancer. OTT. 2018;11:7077–7087.
   Web of Science ®Google Scholar
• Meder L, Schuldt P, Thelen M, et al. Combined VEGF and PD-L1 blockade displays synergistic treatment effects in an autochthonous mouse model of small cell lung cancer. Cancer Res. 2018;78(15):4270–4281.
   PubMed Web of Science ®Google Scholar
• Peterson TE, Kirkpatrick ND, Huang Y, et al. Dual inhibition of ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages. Proc Natl Acad Sci USA. 2016;113(16):4470–4475.
   PubMed Web of Science ®Google Scholar
• Zeng Z, Shi YX, Samudio IJ, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood. 2009;113(24):6215–6224.
   PubMed Web of Science ®Google Scholar
• Chen Y, Jacamo R, Konopleva M, et al. CXCR4 downregulation of let-7a drives chemoresistance in acute myeloid leukemia. J Clin Invest. 2013;123(6):2395–2407.
   PubMed Web of Science ®Google Scholar
• Natsagdorj A, Izumi K, Hiratsuka K, et al. CCL2 induces resistance to the antiproliferative effect of cabazitaxel in prostate cancer cells. Cancer Sci. 2019;110(1):279–288.
   PubMed Web of Science ®Google Scholar
• Cochaud S, Giustiniani J, Thomas C, et al. IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2. Sci Rep. 2013;3:3456.
   PubMed Web of Science ®Google Scholar
• Li ZH, Zhou Y, Ding YX, et al. Roles of integrin in tumor development and the target inhibitors. Chin J Nat Med. 2019;17(4):241–251.
   PubMed Web of Science ®Google Scholar
• Juan-Rivera MC, Martínez-Ferrer M. Integrin inhibitors in prostate cancer. Cancers (Basel). 2018;10(2):44.
   Web of Science ®Google Scholar
• Mason WP. End of the road: confounding results of the CORE trial terminate the arduous journey of cilengitide for glioblastoma. Neuro Oncol. 2015;17(5):634–635.
   PubMed Web of Science ®Google Scholar
• Misra S, Ghatak S, Zoltan-Jones A, et al. Regulation of multidrug resistance in cancer cells by hyaluronan. J Biol Chem. 2003;278(28):25285–25288.
   PubMed Web of Science ®Google Scholar
• Zigrino P, Nischt R, Mauch C. The disintegrin-like and cysteine-rich domains of ADAM-9 mediate interactions between melanoma cells and fibroblasts. J Biol Chem. 2011;286(8):6801–6807.
   PubMed Web of Science ®Google Scholar
• Straussman R, Morikawa T, Shee K, et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature. 2012;487(7408):500–504.
   PubMed Web of Science ®Google Scholar
• Luraghi P, Reato G, Cipriano E, et al. MET signaling in colon cancer stem-like cells blunts the therapeutic response to EGFR inhibitors. Cancer Res. 2014;74(6):1857–1869.
   PubMed Web of Science ®Google Scholar
• Amornsupak K, Insawang T, Thuwajit P, et al. Cancer-associated fibroblasts induce high mobility group box 1 and contribute to resistance to doxorubicin in breast cancer cells. BMC Cancer. 2014;14:955.
   PubMed Web of Science ®Google Scholar
• Wu T, Dai Y. Tumor microenvironment and therapeutic response. Cancer Lett. 2017;387:61–68.
   PubMed Web of Science ®Google Scholar
• Weizman N, Krelin Y, Shabtay-Orbach A, et al. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. Oncogene. 2014;33(29):3812–3819.
   PubMed Web of Science ®Google Scholar
• Yang C, He L, He P, et al. Increased drug resistance in breast cancer by tumor-associated macrophages through IL-10/STAT3/bcl-2 signaling pathway. Med Oncol. 2015;32(2):352.
   PubMed Web of Science ®Google Scholar
• Yin Y, Yao S, Hu Y, et al. The immune-microenvironment confers chemoresistance of colorectal cancer through macrophage-derived IL6. Clin Cancer Res. 2017;23(23):7375–7387.
   PubMed Web of Science ®Google Scholar
• Arlauckas SP, Garris CS. In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy. Sci Transl Med. 2017;9(389):eaal3604.
   Google Scholar
• Roy Chowdhury M, Schumann C, Bhakta-Guha D, et al. Cancer nanotheranostics: strategies, promises and impediments. Biomed Pharmacother. 2016;84:291–304.
   PubMed Web of Science ®Google Scholar
• Kievit FM, Zhang M. Cancer nanotheranostics: improving imaging and therapy by targeted delivery across biological barriers. Adv Mater. 2011;23(36):H217–47.
   PubMed Web of Science ®Google Scholar
• Sun Q, Bai X, Sofias AM, et al. Cancer nanomedicine meets immunotherapy: opportunities and challenges. Acta Pharmacol Sin. 2020;41(7):954–958.
   PubMed Web of Science ®Google Scholar
• Highfill SL, Cui Y, Giles AJ, et al. Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci Transl Med. 2014;6(237):237ra67.
   PubMed Web of Science ®Google Scholar
• Bridge G, Rashid S, Martin SA. DNA mismatch repair and oxidative DNA damage: implications for cancer biology and treatment. Cancers (Basel). 2014;6(3):1597–1614.
   PubMed Web of Science ®Google Scholar
• Shen Y, Yang J, Zhao J, et al. The switch from ER stress-induced apoptosis to autophagy via ROS-mediated JNK/p62 signals: a survival mechanism in methotrexate-resistant choriocarcinoma cells. Exp Cell Res. 2015;334(2):207–218.
   PubMed Web of Science ®Google Scholar
• Shukla SK, Purohit V, Mehla K, et al. MUC1 and HIF-1alpha signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer. Cancer Cell. 2017;32(1):71–87.e7.
   PubMed Web of Science ®Google Scholar
• Xu K, Zhan Y, Yuan Z, et al. Hypoxia induces drug resistance in colorectal cancer through the HIF-1α/miR-338-5p/IL-6 feedback loop. Mol Ther. 2019;27(10):1810–1824.
   PubMed Web of Science ®Google Scholar
• Wu C, Yang T, Liu Y, et al. ARNT/HIF-1β links high-risk 1q21 gain and microenvironmental hypoxia to drug resistance and poor prognosis in multiple myeloma. Cancer Med. 2018;7(8):3899–3911.
   PubMed Web of Science ®Google Scholar
• Jing X, Yang F, Shao C, et al. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019;18(1):157.
   PubMed Web of Science ®Google Scholar
• Benito J, Zeng Z, Konopleva M, et al. Targeting hypoxia in the leukemia microenvironment. Int J Hematol Oncol. 2013;2(4):279–288.
   PubMedGoogle Scholar
• Unruh A, Ressel A, Mohamed HG, et al. The hypoxia-inducible factor-1 alpha is a negative factor for tumor therapy. Oncogene. 2003;22(21):3213–3220.
   PubMed Web of Science ®Google Scholar
• Wallace EM, Rizzi JP, Han G, et al. A small-molecule antagonist of HIF2α is efficacious in preclinical models of renal cell carcinoma. Cancer Res. 2016;76(18):5491–5500.
   PubMed Web of Science ®Google Scholar
• Li YJ, Lei YH, Yao N, et al. Autophagy and multidrug resistance in cancer. Chin J Cancer. 2017;36(1):52.
   PubMedGoogle Scholar
• Yang M, Zeng P, Kang R, et al. S100A8 contributes to drug resistance by promoting autophagy in leukemia cells. PLoS One. 2014;9(5):e97242.
   PubMed Web of Science ®Google Scholar
• Zhu L, Ding R, Yan H, et al. ZHX2 drives cell growth and migration via activating MEK/ERK signal and induces sunitinib resistance by regulating the autophagy in clear cell renal cell carcinoma. Cell Death Dis. 2020;11(5):337.
   PubMed Web of Science ®Google Scholar
• Chen S, Rehman SK, Zhang W, et al. Autophagy is a therapeutic target in anticancer drug resistance. Biochim Biophys Acta. 2010;1806(2):220–229.
   PubMed Web of Science ®Google Scholar
• Pascolo S. Time to use a dose of chloroquine as an adjuvant to anti-cancer chemotherapies. Eur J Pharmacol. 2016;771:139–144.
   PubMed Web of Science ®Google Scholar
• McAfee Q, Zhang Z, Samanta A, et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci USA. 2012;109(21):8253–8258.
   PubMed Web of Science ®Google Scholar
• Duan F, Mei C, Yang L, et al. Vitamin K2 promotes PI3K/AKT/HIF-1α-mediated glycolysis that leads to AMPK-dependent autophagic cell death in bladder cancer cells. Sci Rep. 2020;10(1):7714.
   PubMed Web of Science ®Google Scholar
• Salehan MR, Morse HR. DNA damage repair and tolerance: a role in chemotherapeutic drug resistance. Br J Biomed Sci. 2013;70(1):31–40.
   PubMed Web of Science ®Google Scholar
• Shimizu M, Gruz P, Kamiya H, et al. Erroneous incorporation of oxidized DNA precursors by Y-family DNA polymerases. EMBO Rep. 2003;4(3):269–273.
   PubMed Web of Science ®Google Scholar
• Ketkar A, Maddukuri L, Penthala NR, et al. Inhibition of human DNA polymerases eta and kappa by indole-derived molecules occurs through distinct mechanisms. ACS Chem Biol. 2019;14(6):1337–1351.
   PubMed Web of Science ®Google Scholar
• Takata M, Sasaki MS, Sonoda E, Morrison C, et al. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J. 1998;17(18):5497–5508.
   PubMed Web of Science ®Google Scholar
• Goldstein M, Kastan MB. The DNA damage response: implications for tumor responses to radiation and chemotherapy. Annu Rev Med. 2015;66:129–143.
   PubMed Web of Science ®Google Scholar
• Korsmeyer SJ, Wei MC, Saito M, et al. Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ. 2000;7(12):1166–1173.
   PubMed Web of Science ®Google Scholar
• Dai S, Peng Y, Zhu Y, et al. Glycolysis promotes the progression of pancreatic cancer and reduces cancer cell sensitivity to gemcitabine. Biomed Pharmacother. 2020;121:109521.
   PubMed Web of Science ®Google Scholar
• Tyagi K, Mandal S, Roy A. Recent advancements in therapeutic targeting of the Warburg effect in refractory ovarian cancer: a promise towards disease remission. Biochim Biophys Acta Rev Cancer. 2021;1876(1):188563.
   PubMed Web of Science ®Google Scholar
• Sun X, Sun G, Huang Y, et al. 3-Bromopyruvate regulates the status of glycolysis and BCNU sensitivity in human hepatocellular carcinoma cells. Biochem Pharmacol. 2020;177:113988.
   PubMed Web of Science ®Google Scholar
• Karageorgis G, Reckzeh ES, Ceballos J, et al. Chromopynones are pseudo natural product glucose uptake inhibitors targeting glucose transporters GLUT-1 and -3. Nat Chem. 2018;10(11):1103–1111.
   PubMed Web of Science ®Google Scholar
• Bridges HR, Jones AJ, Pollak MN, et al. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem J. 2014;462(3):475–487.
   PubMed Web of Science ®Google Scholar
• Ben Sahra I, Tanti JF, Bost F. The combination of metformin and 2 deoxyglucose inhibits autophagy and induces AMPK-dependent apoptosis in prostate cancer cells. Autophagy. 2010;6(5):670–671.
   PubMed Web of Science ®Google Scholar
• He J, Shi XY, Li ZM, et al. Proton pump inhibitors can reverse the Yap mediated paclitaxel resistance in epithelial ovarian cancer. BMC Mol Cell Biol. 2019;20(1):49.
   PubMed Web of Science ®Google Scholar
• Hawinkels LJ, Ten Dijke P. Exploring anti-TGF-β therapies in cancer and fibrosis. Growth Factors. 2011;29(4):140–152.
   PubMed Web of Science ®Google Scholar
• Luan X, Sansanaphongpricha K, Myers I, et al. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin. 2017;38(6):754–763.
   PubMed Web of Science ®Google Scholar
• Ciravolo V, Huber V, Ghedini GC, et al. Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy. J Cell Physiol. 2012;227(2):658–667.
   PubMed Web of Science ®Google Scholar
• Wei JX, Lv LH, Wan YL, et al. Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells. Hepatology. 2015;61(4):1284–1294.
   PubMed Web of Science ®Google Scholar
• Orend G, Chiquet-Ehrismann R. Tenascin-C induced signaling in cancer. Cancer Lett. 2006;244(2):143–163.
   PubMed Web of Science ®Google Scholar
• Gao F, Yang C. Anti-VEGF/VEGFR2 monoclonal antibodies and their combinations with PD-1/PD-L1 inhibitors in clinic. Curr Cancer Drug Targets. 2020;20(1):3–18.
   PubMed Web of Science ®Google Scholar