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.

This analysis suggests that most ADRs associated with pimitespib are manageable and reversible, thus supporting its use in patients with advanced GIST.

Through molecular docking analysis, we found that ursolic acid (UA) and tanespimycin might target JAG1, MET, and PLAU...Our study demonstrated that JAG1, MET, and PLAU were significantly overexpressed and associated with poor outcomes in PDAC patients. More importantly, these genes are involved in the crosstalk between tumour and immune cells, which indicates that these genes may serve as novel targets for combination immunotherapy in the treatment of PDAC.

Our ex vivo senolytic screening platform identifies XL888, an HSP90 inhibitor, that clears p16Ink4a+ cancer-associated fibroblasts in vivo. XL888 administration after establishment of advanced LUAD significantly reduces tumor burden concurrent with the loss of plastic tumor cells. Our study identifies a druggable component of the tumor stroma that fulfills the metabolic requirement of tumor cells to acquire a more aggressive phenotype.

Furthermore, our results demonstrated that the combination of Elesclomol with HSP90 inhibitor Ganetespib exhibited synergistic anti-tumor effects. In conclusion, our findings that mitochondria-translocated ALDH1L1 functions as a feedback regulator of redox homeostasis in cancer cells to enhance the resistance to pro-oxidative therapy can provide critical insights into developing effective pro-oxidative therapies against tumors.

In a TNBC xenograft model, 13b significantly reduced tumor volume and weight with a better safety profile than 5-fluorouracil. Molecular docking studies showed that 13b binds within the Hsp90 ATP-binding pocket in a comparable pattern to the known inhibitors, SNX-2112 and GDM. These findings support 13b as a promising and well-tolerated Hsp90-targeted anticancer lead, especially for the treatment of breast cancer.

Compared with the combination treatment group of AR and HSP90 inhibitors (enzalutamide and pimitespib), the nano-PROTAC treatment group presented a high tumor growth inhibition value of up to 78% and a median survival extension of 15 days. Nano-PROTACs that simultaneously degrade AR and HSP90 can overcome the resistance of prostate cancer to PSMA- and AR-positive castration-resistant prostate cancer, except for neuroendocrine prostate cancer, which provides a new therapeutic strategy for the treatment of prostate cancer.

DDO3602 effectively induced PARP1 degradation through a multi-E3 ubiquitin ligase-mediated degradation pathway. In general, this study demonstrates that DDO3602 can degrade the HSP90 nonclient protein PARP1 through the ubiquitin-proteasome pathway and exhibits tumor-selective pharmacokinetics.

In addition, AurAP14 significantly inhibited the tumor growth of NSCLC and drug-resistant NSCLC xenograft tumor mice. The results from this study indicate that AurAP14 represents a promising delivery strategy for the sequential elimination of multiple functions of oncogenic proteins and the attenuation of chemotherapy-induced drug resistance.