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

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]