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Table 1 Comprehensive list of drugs for the TME and their mechanisms of action

From: Underlying mechanisms and drug intervention strategies for the tumour microenvironment

Drug

Inhibitory mechanisms

Mode of action

Test mode

Reference

Oxaliplatin

Immunosuppressive cells

Increase activation of CD8 + T cells, reduce cancer CD11b + F4/80 high macrophages, and reduce spleen MDSCs

In vitro and in vivo test

[86]

PG545

Growth factor-mediated cell invasion

Reduces the phosphorylation of AKT, EGFR and ERK induced by HB-EGF

Phase I clinical trials

[87]

Gemcitabine

EMT

Reduce the frequency of CTC and the logarithm of CTC

In vitro and in vivo test

[88]

Paclitaxel

EMT

Reduce the frequency of CTC and the logarithm of CTC

In vitro and in vivo test

[88]

Fludarabine

Brain cancer cells

X-inactivated specific transcript

In vitro and in vivo test

[89]

Rapamycin

TAMs

Reduction in the expression of Bcl-2 and Survivin and an increase in the expression of Smac

In vitro test

[90]

Apatinib

EMT/Angiogenesis

Targeting STAT3/block PI3K/AKT and VEGFR2/RAF/MEK/ERK signaling pathways

In vitro and in vivo test

[91, 92]

WRG-28

Cancer invasion and migration

DDR2

In vitro and in vivo test

[93]

Bortezomib

CAF

Caspase-3

In vitro and in vivo test

[94]

Pambarbital

CAF

Caspase-3

In vitro and in vivo test

[94]

Apelin inhibitor

Angiogenesis/MDSCs

Apelin

In vitro and in vivo test

[95]

Dasatinib

TAMS

Inhibited the self-renewal ability of H460R and A549R cells

In vitro test

[96]

Repagenil

Cancer cell

MSCs

In vitro and in vivo test

[97]

Anti-CTLA-4 antibody

T cells

Enhance antibody-dependent cell-mediated cytotoxicity, phagocytosis

Preclinical trial

[98]

Transforming growth factor-β inhibitors

Cancer cell/releasing cytotoxic T cells/promote T cell infiltration

Transforming growth factor-β

In vitro and in vivo test

[99, 100]

Plerixafor

Angiogenesis

CXCR4

In vitro and in vivo test

[101]

Macrophage receptor with collagen structure

Cancer proliferation

E-programming of macrophages

In vitro and in vivo test

[102]

Embeline

Growth of pancreatic cancer

Increasing the infiltration of Th1 cells, NK, CTL, γ δ T and NKT, and reducing the infiltration of Th17, PMN-MDSC, IL-8 and IL-6 positive immune cells

In vitro and in vivo test

[103]

Functionalized micellar

Reverse the abnormal expression of several key marker proteins

Inhibit the adhesion of activated endothelial cells to circulating cancer cell

In vitro and in vivo test

[104]

Cancer matrix-targeted nano-carrier

Cut off the support of the matrix to cancer cells

Remove CAFs,

In vitro and in vivo test

[105]

Nanoparticles-based photoimmunotherapy

T cells

CAFs

In vitro and in vivo test

[106]

Curcumin

Cancer cells, Angiogenesis

VEGF, IL-6 and cancer stem cells, transcription factor nuclear factor-NB (NF-NB), signal transduction, transcriptional activator 3 and angiogenic cytokines

In vitro and in vivo test

[107, 108]

APG-157

Attract immune cells into the TME

Increased expression of CD4+ and CD8+ cells and increased expression of PD-1 and PD-L1

Phase I placebo controlled trial

[109]

Sophoridine

Macrophage

TLR4/IRF3 pathway

In vitro test

[110]

Ginsenoside Rh2

Improve TME

Regulating the phenotype of TAMs

In vitro and in vivo test

[111]

Berberine

EMT

Smad-independent and Smad-dependent transforming growth factor-β signaling pathway

In vitro test

[112]

Wogonin

EMT

IL-6/STAT3 signal pathway

In vitro and in vivo test

[113]

Bigelovin

EMT

N-and E-cadherin, STAT3 pathway, and cofilin pathway

In vitro and in vivo test

[114]

Cordycepin

Up-regulating cancer cell apoptosis and eliciting cell cycle arrest

CSCs

In vitro test

[115]

Shikonin

Cancer cell

Exosome

In vitro test

[116]

6-gingerol (6G)

TME

Promoting cancer vascular normalization, reducing microvascular structure entropy (MSE)

In vitro and in vivo test

[117]

Salvianolic acid A

Angiogenesis

Block the secretion of glucose-regulated protein 78

In vitro and in vivo test

[118]

Dihydrodiosgenin

Inhibit HCC metastasis

Inhibit platelet activation and reduce endothelial cell-derived factor VIII

In vitro and in vivo test

[119]

Poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitor (PARPI)

Up-regulate PD-L1

Promoting the activation of IFN pathway, Up-regulate PD-L1

Preclinical trial

[120, 121]

The combination of PARPI and mitogen-activated protein kinase (MEK) inhibitor

TME

Induces BIM-mediated apoptosis by activating caspase-3, inhibits the expression of CD31 in endothelial cells, and inhibits the production of mutant RAS-induced VEGF through RAS/MAPK pathway

In vitro and in vivo test

[122]

Sorafenib combined with bufalin

Angiogenesis

mTOR/VEGF signal pathway

In vitro and in vivo test

[123]

Ginsenoside Rg3 combined with cisplatin

TME

EMT

In vitro and in vivo test

[124]