LNP-siPP2Ac efficiently silenced PP2Ac in vitro and, when delivered locally in vivo, prolonged survival in a CD8+ T cell-dependent manner. Together, these findings identify PP2A as a regulator of immunogenic senescence in MB and support PP2Ac targeting as a therapeutic strategy.

Variation in experimental platforms, sample representation, and data integration across public datasets is a recognised study limitation. Nonetheless, LB-100 may provide a novel therapeutic avenue in CML, provided further preclinical functional and clinical validation is performed in patient-derived samples to confirm translational applicability of the findings.

Importantly, using a drug-repurposing approach, we found that inhibition of CA5B, PPP3CA, and PP2A by acetazolamide, tacrolimus, and LB-100, respectively, showed high toxicity toward KMT2A::AFF1+ leukemic blasts and reduced leukemia burden in vivo...This study highlights how the unique microRNA expression signature of patients with KMT2A::AFF1+ BCP-ALL can be used to uncover novel therapeutic avenues and accelerate drug repurposing. It also indicates potential new drug combinations for less toxic chemotherapy.

P1, N=3, Active, not recruiting, City of Hope Medical Center | Trial completion date: Mar 2026 --> Jan 2027 | Trial primary completion date: Mar 2026 --> Jan 2027

Treatment with DT-061 combined with its inactive competitive antagonist, DT-766, and the proteasome inhibitor, MG-132, reversed this effect on the loss of N-Myc protein expression, suggesting that PP2A-B56α modulation affects N-Myc stability via the proteasomal degradation pathway. In a xenograft model, we observed tumor growth inhibition upon DT-061 treatment, along with a reduction in N-Myc protein expression in vivo. Combined, these results highlight the importance of the PP2A tumor suppressor in regulating MYCN oncogenic signaling and open new potential treatment regimens for high-risk neuroblastoma patients.

P1, N=57, Active, not recruiting, Institut Curie | Recruiting --> Active, not recruiting | N=101 --> 57 | Trial completion date: Dec 2025 --> Jan 2027 | Trial primary completion date: Nov 2025 --> Dec 2026

P1/2, N=21, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Oct 2027 | Trial primary completion date: Jan 2026 --> Oct 2027

P1, N=101, Recruiting, Institut Curie | Trial primary completion date: Jul 2025 --> Nov 2025

This study also preliminarily validated the effect of the combination of the two drugs on other subtypes of CTCL. Overall, these findings provide potential new therapeutic strategies for CTCL (especially SS), although further clinical evaluation is required to validate these results.

In conclusion, our study indicates that Canagliflozin ameliorate HF via inhibiting PP2A-mediated dephosphorylation of β-catenin in HSCs. The inhibition of PP2A in HSCs may represent a potential therapeutic target not only for cancer treatment but also for the management of HF.

We found that in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) cells, CIP2A degradation via ubiquitination enhanced PP2A phosphatase activity, leading to the dephosphorylation of ATR at Ser428 in the cytoplasm...These findings reveal a novel mechanism of resistance to DNA damage-based cancer drugs and introduce a new action mechanism of LB-100, which works through mtATR-tBid complex-mediated apoptotic dormancy triggered by CIP2A degradation-mediated PP2A activation. Disrupting the mtATR-tBid complex may represent a promising strategy to restore or sensitize resistant cancer cells to apoptosis.