Thus, the ARF6-based pathway affects the TME and the intrinsic function of tumors, leading to malignancy. Here, we discuss the potential mechanisms of this ARF6-based pathway in tumorigenesis, and novel therapeutic strategies.

Finally, our screens identified 48 other possible targets of NAV-2729. These results illustrate the complexities of defining targets of small molecules and identify NAV-2729 as a model PH domain- binding inhibitor.

Overall, the small molecule inhibitors of lipid handling proteins BMS309403, HTS01037, NAV2729, SB-FI-26, and sulfosuccinimidyl oleate (SSO) caused a drug-specific, dose-/time-dependent inhibition of FA/LDL uptake, associated with reduced proliferation, cell cycle arrest, and apoptosis. Our findings indicate that OC cells are very sensitive to lipid deficiency. This dependency should be exploited for development of novel strategies against OC.

In this review, we summarize our recent understanding of how PDAC cells acquire and augment mesenchymal features via metabolic and immunological changes during tumor progression, and how mesenchymal malignancies induce metabolic network rewiring and facilitate an immune evasive TME. In addition, we also present our recent findings on the interesting relevance of the small G protein ADP-ribosylation factor 6-based signaling pathway driven by KRAS/TP53 mutations, inflammatory amplification signals mediated by the proinflammatory cytokine interleukin 6 and RNA-binding protein ARID5A on PDAC metabolic reprogramming and immune evasion, and finally discuss potential therapeutic strategies for the quasi-mesenchymal subtype of PDAC.

Importantly, XIST silencing blocked xenograft tumor growth in vivo. XIST knockdown inhibited chordoma progression via regulating the miR-320d/ARF6 axis, providing a novel insight into chordoma pathogenesis.

Additionally, our research demonstrated that ARF6 may control capecitabine resistance via several routes. ARF6 may play a critical role in the development of GC.

Moreover, recipient MCF-7 cells could effectively uptake these miR-760-rich exosomes that significantly promoted proliferation, tumor growth in vivo, migration, invasion, and chemoresistance by activating ARF6-mediated Src/PI3K/Akt signaling and the epithelial-mesenchymal transition (EMT) pathway. Together, our results support that exosomal miR-760 secreted by CCL18-stimulated high metastatic BC cells promoted the malignant behaviors in low metastatic BC cells by up-regulating the ARF6-mediated Src/PI3K/Akt signaling pathway.

Tris DBA significantly inhibited tumor growth in xenograft MM and orthotopic HCC preclinical mice models with a reduction in the expression of various prosurvival biomarkers in MM tumor tissues without displaying significant toxicity. Overall, Tris DBA functions as a good inhibitor of STAT3 signaling in preclinical HCC and MM models.

Finally, rescue experiments demonstrated that ARF6 overexpression attenuated the effects of the miR-28-3p mimic by upregulating Rac1 and p-Erk1/2 expression in PCa cells. In conclusion, these findings indicated that miR-28-3p may inhibit the biological behaviors of PCa cells by targeting ARF6, and therefore may represent a novel therapeutic candidate for PCa.

This is the first report showing that high gene expression of ARF6 in PDAC indicates a different immune profile, is enriched in cancer metastases, and is associated with poor survival . Our results provide the first clinical evidence supporting the ARF6 pathway as a major downstream target of KRAS and TP53 mutations promoting immune evasion, suggesting ARF6 is a novel marker for prognosis and a potential target for immune therapeutic strategies in PDAC.

SEV suppressed the migration, invasion, and EMT of BC cells through downregulating the abundance of ARF6 by upregulating miR-139-5p. The miR-139-5p/ARF6 axis might be a promising target for the treatment of BC.

In conclusion, Tris DBA effectively ameliorated the mouse IgAN model and targeted signalling pathways downstream of ICs-mediated interaction, which is a novel immunomodulatory strategy. Further development of Tris DBA as a therapeutic candidate for IgAN is warranted.

Surprisingly, the HANP containing IGF1R antibody was less effective than particles without antibody, possibly due to steric hindrance of IGF1R and CD44 binding. Tris DBA-Pd nanoparticles are an effective therapy for CD44-positive tumors like melanoma, and further development of these nanoparticles should be pursued.