IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)

P1/2, N=606, Recruiting, Sumitomo Pharma America, Inc. | N=362 --> 606

P2, N=14, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Mar 2027

P1/2, N=112, Not yet recruiting, Shanghai Jiao Tong University School of Medicine

Pathological subtypes of CCA exhibit distinct clinical outcomes and molecular characteristics. Classification based on pathological subtype provides a useful framework for understanding the clinical and molecular heterogeneity of CCA.

P1, N=25, Recruiting, Servier Bio-Innovation LLC

P2, N=80, Recruiting, Mayo Clinic | Trial completion date: Mar 2027 --> Nov 2033 | Trial primary completion date: Mar 2027 --> Feb 2031

We leveraged an EHR-derived database to evaluate real-world outcomes in patients receiving TKIs for AML. Our study found no significant differences between real-world Event Free Survival (rwEFS) and real world Overall Survival (rwOS) across patients of different racial/ethnic groups, this suggests that when patients have access to targeted therapy outcomes across different racial/ethnic groups become more equitable.

The patient had an initial partial response to the C5 inhibitor eculizumab, but the disease progressed...The patient received a total of six sessions of therapeutic plasma exchange and two concurrent doses of defibrotide during the Iptacopan course...This biochemical improvement coincided with key clinical outcomes: resolution of proteinuria and the achievement of sustained red blood cell transfusion independence after day +58 and platelet transfusion independence after day +66, marking a decisive turnaround in his TA-TMA course. Treatment with the novel oral complement inhibitor Iptacopan induced significant hematological and clinical responses in this TA-TMA patient, demonstrating its potential therapeutic efficacy and warranting further clinical investigation.

In a syngeneic immunocompetent glioblastoma mouse model, brain delivery of antisense oligonucleotide targeting Dnmt3a expression led to microglial activation and reduced tumor growth. Taken together, our results reveal the involvement of DNA demethylation in the control of glioma cells-induced microglia activation and indicate that microglial DNMT3A is a potentially therapeutic target to treat brain neoplasms such as glioblastoma that include a microglial component.

Phosphoproteomics revealed reduced phosphorylation of MRCKA and SLK substrates, suggesting crosstalk between D/L-2HG modification and kinase activity. These findings highlight distinctive roles of D/L-2HG modifications in cancer progression and suggest potential avenues for therapeutic targeting of oncometabolite-induced post-translational modifications.

Our study establishes ANXA5 as a prime example of a translatable biomarker discovered through multi-omics integration. It functions dually as a prognostic indicator and a predictive biomarker for immunotherapy, offering a tangible framework for patient stratification and personalized therapeutic strategies in glioma, thereby bridging a critical gap toward clinical translation.

Gemcitabine-based chemotherapy is the standard treatment regime for advanced intrahepatic cholangiocarcinoma (iCCA), but the frequent presence of chemoresistance limits its efficacy. The low level of Mg2+, an ion that competitively hinders binding of ivosidenib on wtIDH1, in iCCA tumor microenvironment contributed to the expanded therapeutic window of ivosidenib in patients with iCCA. Our work revealed the potency of combining targeting IDH1 and chemotherapy against wtIDH1 iCCA and other tumors.