DNAJB1 (DnaJ Heat Shock Protein Family (Hsp40) Member B1)

Our findings demonstrate that immune resistance in FLC is mediated by both local T-cell exclusion and exhaustion, with combination CXCR4 and PD-1 blockade acting cooperatively to overcome these independent mechanisms. These results highlight the versatility of the human TSC system to aid in the study of rare cancer types and provide important preclinical evidence for the rational design of combination immunotherapy in FLC, which currently lacks any effective systemic therapy.

P1, N=20, Recruiting, University Hospital Tuebingen | Not yet recruiting --> Recruiting

These results indicate that vildagliptin-induced liver injury occurs via a mechanism whereby the covalent binding of vildagliptin induces the release of HSP40 from hepatocytes, in turn activating inflammasomes. We further demonstrated that the risk of vildagliptin-induced liver injury may be increased by impaired immune tolerance, such as that caused by the co-administration of immune checkpoint inhibitors.

PAL is suggested as a promising new therapeutic agent for malignant melanoma.

Furthermore, we predicted and experimentally confirmed that DNAJB6 silencing conferred gefitinib resistance in HepG2 cells. In conclusion, our findings highlighted the significance of DNAJB6 expression in determining LIHC prognosis and immunotherapy response, as well as its potential in developing novel anti-cancer drugs and enhancing immunotherapy.

NRG1 fusions are oncogenic drivers in non-small cell lung cancer (NSCLC), with therapeutic relevance highlighted by the FDA's designation of Zenocutuzumab for NRG1 fusion-positive cases...No significant difference in progression-free survival was seen following first-line EGFR TKI therapy between uncommon and wild-type groups. Our findings highlight the heterogeneity of NRG1 fusions in NSCLC, revealing novel fusions, unique pathway enrichments, and expression profiles that may inform future personalized treatment strategies.

Prior molecular studies have focused mainly on the DNAJB1-PRKACA fusion gene, which is pathognomonic for FLC, but no reliable circulating biomarker has been established for FLC diagnosis or disease monitoring...Routine measurement of serum PCT could facilitate earlier recognition of FLC and also provide a non-invasive tool to track treatment response. Future research should validate these findings prospectively, explore the biological mechanisms underlying CALCA overexpression in FLC, and assess whether PCT-guided monitoring can predict prognosis, improve patient outcomes or clinical trial design in this rare malignancy.

While HSP-targeted therapies offer significant promise, challenges such as drug resistance, toxicity, and compensatory upregulation of other chaperones remain formidable obstacles. Future research should focus on refining therapeutic selectivity, optimizing combination regimens, and utilizing advanced technologies, such as CRISPR-based gene editing and nanotechnology, to enhance treatment efficacy.

Therefore, studying other HSP40/JDPs that are involved in the advancement of cancer and the activities of p53 (both mutant and wild type), together with their related processes, would enhance our understanding of how cancer progresses, we might potentially speed up the development of innovative treatments for cancer. It is expected that pharmacological molecules and their analogues that specifically target p53 aggregation might be utilised with other anticancer drugs to address the issue of p53 aggregation.

This study uncovers a distinct immunoregulatory network in CASH, providing potential avenues for mitigating chemotherapy side effects and developing novel immunotherapeutic strategies for patients with liver metastases.

In this article, we attempt to summarize the patterns in the latest research reports based on the molecular characteristics and regulatory mechanisms of HSPs, and screen HSPs with potential for diagnosis, accurate tumor staging, future targeted drug design, and development. We hope to provide ideas for future research on related tumors and their clinical treatments.

The presence of DNAJ-PKAc creates a vulnerability to the combination of glutamine antimetabolite and ICI therapy in FLC.