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Table 1 A list of drugs being resistant in tumors by non-cell-autonomous methods

From: Tumor microenvironment-driven non-cell-autonomous resistance to antineoplastic treatment

Drug Tumor with resistance Cancer cell lines Experimental objects Non-cell- autonomous factors Signaling pathway Reference
Bevacizumab Ovarian cancer, GBM SKOV-3, OVCAR-3, GOC-2, GOC-A2, U87-MG, U251, LN229, Cell, xenograft tumor UVEC, TAM AKT/FGF2, MIF [88, 125]
Bortezomib Multiple myeloma (MM) , MCL RPMI-8226, U266, 5T33MM mouse primary tumor cell Cell, xenograft tumor, clinical sample BMSC, TAM MUC-1, IL-6, JAK2/STAT3, NF-κB [88, 89, 146,147,148,149]
Cetuximab Head and neck squamous cell carcinomas (HNSCC), lung squamous cell carcinoma, gastric cancer, NSCLC UTSCC cell lines, EBC1, GTL16, HCC827 Cell, xenograft tumor CAF MMP family, HGF/MET, NF-κB [107]
Cytarabine Acute myelogenous leukemia (AML) OCI-AML cell lines, Molm13, KG-1, HL-60, ML-1, Mono-Mac-6, Kasumi-1, NB-4, MV-4/11, HEL, CMK, M-07e, primary AML cell Cell, xenograft tumor MSC, hypoxia Autophagy, FLT3/PI3K, Mcl-1 [63, 64, 150]
Doxorubicin MM, osteosarcoma, aggressive N-Myc amplified neuroblastoma, melanoma, breast cancer, pancreatic cancer, NSCLC, colon cancer, soft tissue sarcoma, prostate carcinoma NCI-H460, RH460, K562, K562Dox, MCF-7, Saos-2, U2-OS, U266, RPMI-8226, DP42, MM1.S, NCI-H929, 38ATLN, MDA-MB-231, CRL-2539, A375, U251, HCT116, HEK293T, BxPC-3, AsPC-1, A549, H2170, KLN205, CT26, WT-CLS1, SH-SY5Y, SK-N-BE2, SKLMS-1, RD, LNCaP, 22Rv1 Cell, xenograft tumor, clinical sample ECM, CAF, MSC, hypoxia, MDSC IL-6/STAT3, NF-κB/ IκB, IL1β, CXCL1/GROα, PI3K/Rac, VEGF, HIF-1α/miR424/PDCD4, cathepsin family, hyaluronic acid (HA), Rho/ROCK, miRNA/PTEN [69, 70, 76,77,78]
Epirubicin Breast cancer MCF-7 and MDA-MB-468 Cell CAF Estrogen/GPER/cAMP/PKA/CREB [84]
Erlotinib Cholangiocarcinoma (CCA) HuCC-T1, EGI-1, SK-ChA-1, Mz-ChA-1 Cell, xenograft tumor, clinical sample CAF IR/IGF2/IGF1R [111]
Etoposide Hepatoma, lung carcinoma, prostate carcinoma, melanoma, breast cancer HepG2, A549, PC3MLN4, A375SM, MCF-7, RPMI-8226, MDA-MB-231, SUM-159PT Cell, xenograft tumor Hypoxia, myeloma cell p53, acylglycerol-3-phosphate acyltransferase 2, p27/kip1, [92, 93]
Fludarabine Chronic lymphocytic leukemia (CLL) NOX-A12, Jurkat cell, Nalm6, Cell, clinical sample BMSC, CLL B-cell, MSC CXCL12/CXCR4, Akt/FoxO3a/Bim, IL-8, CCL4, CCL11, CXCL10, GSH [151]
Gefitinib Non-small cell lung cancer (NSCLC), breast cancer SUM102, SUM149, PC-9, HCC827 Cell CAF, hypoxia FGF2, HGF/Met, IGF1/HIF-1α, podoplanin [109, 110, 152, 153]
Gemcitabine Pancreatic cancer, thymoma, lung cancer, melanoma, breast cancer AsPC1, BxPC3, Panc1, MIAPaCa2, CFPAC1, HPAC1, THP1, K989, Capan2, SW1990, NIH-3T3, THP1, EL4, LLC, B16F10, 4T1 Cell, xenograft tumor, clinical sample CAF, TAM, MDSC Tissue transglutaminase /SATB-1/SDF-1/CXCR4, miR-365/CDA, IL-17, IL-1β [57, 58, 154,155,156,157]
Ibrutinib mantle cell lymphoma (MCL), CLL HBL-2, Jeko-1, Mino, SP49 Cell, xenograft tumor, clinical sample BMSC, nurse-like cell PI3K/AKT/mTOR, integrin-β1, NF-κB, Bcl-2 [151]
Imatinib Chronic myelogenous leukemia (CML) K562, KU812   BMSC NF-κB/STAT5, HO-1, PI3K/AKT, Bcl-2, CXCL12/CXCR4 [151]
Lapatinib Esophageal squamous-cell carcinoma (ESCC), breast cancer TE cell lines, EC-GI-10, KYSE cell lines, T.T, TTN, MCF10, MDA-MB-453, HCC1954, MCF7, T47D, SUM cell lines Cell, xenograft tumor CAF, ECM HGF/Met, FGF/FGFR, Bcl-2/Bcl-x, PI3K/AKT, JAK/STAT, laminin/Bcl-2 [101,102,103, 158,159,160]
Mitoxantrone Prostate cancer Prostate cancer cell lines M12, 22Rv1, M2205, PC-3, DU145, LNCaP, PSC27, Hs5 and Hs27a Cell, clinical sample CAF, Apoptosis [83]
Oxaliplatin Colorectal cancer human colorectal cancer cells HCT 116 and SW620, Cell CAF, hypoxia Nrf2, HIF [37, 38, 40]
Cisplatin Esophageal squamous cell carcinoma, Ovarian cancer, epithelial ovarian cancer MCF-7, BC-MSCs, A2780 ovarian cancer cell lines Cell CAF, miRNA AKT, ERK1/2, IL-6, STAT3, p38, JNK, STAT3, NF-κB [36, 38,39,40,41,42,43,44,45,46,47,48]
Paclitaxel Breast cancer, renal cell carcinoma (RCC) MMTV-PyMT mouse primary tumor cell lines, MDA-MB-231 Cell, primary tumor, xenograft tumor TAM Cathepsin B and S [90, 91]
Sorafenib Hepatocellular carcinoma (HCC), prostate cancer, AML, thyroid carcinoma 22Rv1, PC-3, HCA-1, JHH-7, Hep3B, Huh7, PLC/PRF/5, HepG2, MHCC97H, HCCLM3, Hepa1-6, H22, Molm13, SMMC-7721, KTC1, TPC1 Cell, xenograft tumor, primary tumor, clinical sample TAN, CAF, HSC, hypoxia, pericyte SDF1α/CXCR4, Bcl-2, HIF-1α/NF-κB/CXCL5, CCL2&CCL17, BMX/STAT5, HIF-1α/hydroxyproline, collagen I, TGF-β1/CTGF, TSP- 1/TGFβ1, ERK, AKT, SMAD3 [112,113,114,115,116,117,118,119, 161, 162]
Sunitinib RCC, GBM, breast cancer, colon cancer, melanoma, lymphomas, lung carcinoma U87MG, 4T1, CT26, RENCA, 786-O, ACHN, 771R-Rluc, EL4, LLC, B16F1, TIB6 Cell, xenograft tumor, clinical sample MDSC, macrophage STAT5/IFN-γ [90, 91]
Temozolomide Glioblastoma (GBM) U251, U87, GBM8401, U87MG, HEK293T, A172 Cell, xenograft tumor Hypoxia, perivascular cell, astrocyte ROS, HIF-1α, NF-κB, Bcl-x, miR-26a/Bad/Bax, MGMT, EGFR, PI3K/AKT, Ras/Raf, connexin43, [51,52,53,54, 163,164,165]
Trastuzumab Breast cancer BT-474, SK-BR-3, MDA-MB-453, MDA-MB-361 Cell, xenograft tumor Adipocyte IFN-γ [100]
Vatalanib GBM PDGC23, U87MG Cell, primary tumor Myeloid cell Colony stimulating factor-1 [90, 91]
Vemurafenib Melanoma, thyroid carcinoma A375M6, WM266-4, M21, SkMel28, FS cell lines, M93-047, UACC cell lines, WM cell lines, 1205LU, YUMM1.7, KTC1, TPC1 Cell, xenograft tumor Acidosis, CAF in aged TME, pericyte mTOR, AKT, sFRP2/ROS, TSP- 1/TGFβ1, ERK, SMAD3 [121, 122]