We developed NN-01-195 as a novel chimeric small molecule that combines an AURKA inhibitor related to TAS-119/VIC-1911 with an HSP90-binding moiety related to SNX2112, and evaluated its function. Further, in combination with an inhibitor of the G2/M checkpoint protein WEE1, NN-01-195 is more potent than VIC-1911 in limiting growth of xenograft tumors. These data support the exploration of NN-01-195 and improved analogs as promising new candidates for therapeutic evaluation.

P1, N=78, Active, not recruiting, Taiho Pharmaceutical Co., Ltd. | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026 | Recruiting --> Active, not recruiting

NIR irradiation induces pyroptosis via caspase-3/GSDME activation and immunogenic cell death, while Ganetespib suppresses glycolysis (HK2/PKM2 downregulation) to reverse lactate-driven immunosuppression. This dual-action strategy synergistically enhances T-cell infiltration and ablates residual/metastatic lesions, offering a transformative approach for unresectable Osteosarcoma.

P1, N=63, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Here, we study EV secretion from individual breast cancer cells and the changes under treatment with the HSP90-inhibiting cancer drug tanespimycin (17AAG)...Moreover, our results emphasize that using CD63 as the sole EV capture protein may hide important EV subpopulations. Overall, our platform may support future choices of EV biomarkers for diagnostic and biomedical purposes and help in understanding the heterogeneous drug response of cancer cells.

Paired liver biopsies revealed no significant changes across treatment groups. While the combination of XL888 and pembrolizumab was safe and induced systemic immune modulation, limited clinical efficacy was observed and did not impact the PDAC TME.

A critical unanswered question remains: which form of the dual inhibitions caused the observed toxicity in humans that led to the spectacular failure of the trials and which underlies the limited efficacy that might be the real reason for the only approval of the orally administered ATP-binding inhibitor, Pimitespib (TAS-116), in 2022 by Japan? We suggest that addressing this question could prompt a paradigm shift in the design of next-generation anti-Hsp90 cancer therapeutics.

P1, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Nov 2025 --> Nov 2026

This protocol combines flow cytometry and confocal microscopy to quantitatively and visually assess ganetespib uptake, providing insight into drug distribution and therapeutic response in human cancers. For complete details on the use and execution of this protocol, please refer to 1,2.

ADG suppresses HSP90 expression, and tanespimycin prevents ADG-induced cytotoxicity, showing that HSP90 is ADG's main target in activating intracellular activities...The findings strongly suggest that ADG may treat PC. ADG's pharmacokinetics and other effects must be studied in patients' clinical trials to make it a pancreatic cancer therapy option.

According to our results, such outstanding improvements were attributed to (i) restoring cellular oxidant balance (GSH, MDA & NO), (ii) curbing NF-κB/TNF-α/MCP-1 inflammatory cascade, (iii) HSP90 inhibition with reduced expression of glucocorticoid receptors (GR), (iv) reduced expression of the endoplasmic reticulum stress sensors (CHOP & PERK), (v) activation of protein degradation pathways that degrade the misfolded GR including proteasomal degradation (20 S proteasome) and autophagy (BECLIN1). In conclusion, the findings in this study provide valuable insights into the therapeutic potential of LUM in protecting against DEX-induced deleterious effects on hepatic and aortic tissue in order to get the optimum therapeutic outcome from DEX.

Given the lack of significant effects on direct DNA repair or transcriptomic responses, our findings suggest that HSP90 inhibition radiosensitizes NET cells by inducing a pleiotropic effect on multiple stress-related pathways at the protein level, rather than solely through disruption of DNA damage response mechanisms. This effect is likely driven by loss of HSP90 function and subsequent cumulated unfolded protein and proteotoxic stress.