P1, N=30, Recruiting, Virginia Commonwealth University | Not yet recruiting --> Recruiting

P1, N=30, Not yet recruiting, Virginia Commonwealth University | Initiation date: Dec 2024 --> Mar 2025

P1, N=30, Not yet recruiting, Virginia Commonwealth University

GZ17-6.02 interacted with doxorubicin or ERBB family inhibitors to significantly enhance tumor cell killing which was associated with greater levels of autophagosome formation and autophagic flux...The components of GZ17-6.02 were detected in tumors using a syngeneic tumor model. Our data support future testing GZ17-6.02 in uveal melanoma as a single agent, in combination with ERBB family inhibitors, in combination with cytotoxic drugs, or with an anti-PD1 immunotherapy.

The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.

The drug combination of GZ17-6.02 and bortezomib activated ATM, the AMPK and PERK and inactivated ULK1, mTORC1, eIF2α, NFκB and the Hippo pathway. HDAC knock down also enhanced ATG13 phosphorylation, increased BAK levels and reduced those of BCL-XL. Collectively, our present studies support performing additional in vivo studies with multiple myeloma cells.

Inhibition of autophagy and knock down of death-mediators downstream of the mitochondrion, AIF and caspase 3, almost abolished tumor cell killing. Hence in MF cells, GZ17-6.02 is a multi-factorial killer, utilizing ER stress, macroautophagy, death receptor signaling and directly causing mitochondrial dysfunction.

In a subcutaneous tumor model, GZ17-6.02 decreased tumor volume (p = .002) and weight (p = .009) compared to control conditions. Proteomic analysis of tumor samples showed that GZ17-6.02 suppressed the expression of several proteins that may promote CTCL growth, including mitogen-activated protein kinase (MAPK)1, MAPK3, Growth factor receptor bound protein (GRB)2, and Mediator of RAP80 interactions and targeting subunit of 40 kDa (MERIT)40.

We conclude that intraventricular application of a SHH pathway inhibitor combines the advantages of a specific treatment agent with precise drug delivery and might evolve as a promising new way of targeted treatment for SHH MB patients.

We recently showed that GZ17-6.02, an anticancer agent composed of curcumin, haramine, and isovanillin, inhibited the growth of H297.T cells...RNA sequencing and proteomic analyses revealed that GZ21T suppressed several pathways, including MAPK (P = 0.025), phosphoinositide 3-kinase-protein kinase B (P = 0.04), HIF-1α (P = 0.016), Wnt (P = 0.025), insulin (P = 0.018), and ERBB (P = 0.016) signaling. GZ21T also upregulated the autophagy-promoting protein AMPK while suppressing proteins such as PD-L1, glutaminase, pAkt1 S473, and eEF2K.

Orthotopic xenografts were treated with Lipotecan and/or RT...TOP1i reinforces NK cell-activated anti-HCC effect of RT through RNF144A mediated DNA-PKcs ubiquitination. RNF144A provides a reason for differentiating radiosensitization effect between HCC cells.

Blockade of both autophagy and death receptor signaling abolished drug-induced actinic keratosis cell death. Our data demonstrate that the unique combination of isovanillin, curcumin, and harmine represents a novel therapeutic with the potential to treat actinic keratosis in a manner different from the individual components or pairs of the components.