P2, N=24, Not yet recruiting, National Institute of Neurological Disorders and Stroke (NINDS)

Entecavir antiviral therapy led to suppressed viral replication and improved liver function during follow-up. This case emphasizes the need for HBV screening and close monitoring of viral markers/liver function in asymptomatic HBV carriers receiving dalpiciclib, as early antiviral intervention prevents severe liver complications. It also highlights the importance of clinical pharmacist-led medication follow-up management for outpatients receiving targeted anticancer therapy to avoid oversight of comorbidities and associated prophylactic treatment.

In Jurkat xenograft models, SAp-CD28 demonstrated potent antitumor activity, and its combination with cytarabine resulted in near-complete tumor suppression, highlighting its potential for T-ALL treatment. This work introduces a CD28-targeted, enzyme-activated nanotherapeutic strategy that synergizes biochemical and mechanical mechanisms to selectively eliminate T-ALL cells. This multi-mechanistic tumor-killing strategy can also be extended to inspire therapeutic approaches for other diseases.

To develop novel anti-leukemia therapies, a CNN model identified C191-0266 targeting METTL3, which exhibited potent anti-leukemia activity. It inhibited the proliferation of OCI-AML3, MOLM-13, and THP-1 cell lines with IC50 values of 16.91 μM, 19.01 μM, and 24.99 μM respectively, showed strong METTL3 binding (KD = 7.28 μM) and enzymatic inhibition (IC50 = 7.639 μM), enhanced Ara-C's cytotoxicity by suppressing Ara-C-induced protective autophagy, maintained stable binding to METTL3, regulated the NF-κB pathway to inhibit TNF-α overexpression in Ara-C-resistant cell lines, and had favorable pharmacokinetics and safety profiles via ADME assessments, thus holding promise as an anti-leukemia drug candidate.

This facilitates autophagolysosome formation and enhances autophagic flux to reduce AraC-induced apoptosis, resulting in drug resistance. Targeting LAPTM5 represents a promising strategy to overcome this autophagy-mediated resistance.

TAF may serve as a promising novel therapeutic agent for the treatment of AML.

Venetoclax-based regimens, combined venetoclax with either hypomethylating agents or low-dose cytarabine, have markedly improved treatment outcomes in elderly patients with acute myeloid leukemia (AML). Importantly, the combination of bortezomib and venetoclax significantly prolongs the survival of mice inoculated with venetoclax-resistant AML cell line harboring BAX mutations, which are commonly observed in relapsed AML following venetoclax-based regimens and confer resistance to venetoclax by inhibiting BAX-dependent apoptotic pathway. Collectively, this study provides a rationale for venetoclax-bortezomib combination as a potential strategy to overcome venetoclax resistance in certain AML subsets.

These findings underscore the potential of GNL as a hepatoprotective drug against cytarabine-induced hepatotoxicity, mediated by its antioxidant and anti-inflammatory effects through modulation of the PI3K/AKT and NF-κB pathways. Future research should investigate its therapeutic potential in alleviating chemotherapy-induced liver damage.

The combination of famciclovir and nerve block therapy substantially improves pain relief, reduces inflammatory responses, and enhances clinical outcome without increasing the risk of adverse events.

Using an unbiased approach, we identify Src-family kinase member LYN, and guanine nucleotide-binding protein G(i) alpha subunit proteins, GNAI1, GNAI2, and GNAI3 as novel binding partners of MSLN in AML and show that pharmacological or genetic inhibition of LYN signaling restores NOMO-1 cell sensitivity to Ara-C. Together, these findings demonstrate that MSLN functions as an oncogenic driver in AML and reveal a previously unrecognized MSLN-LYN signaling axis, the therapeutic targeting of which may enhance responses to chemotherapy.

Analysis of primary AML samples or cell lines revealed that BMPR1B and TAZ/TEAD but not YAP levels were higher after patient relapse or in cells resistant to cytarabine or venetoclax. Finally, using a 3D human bone marrow-like model, we showed that targeting BMPR1B or TAZ/TEAD in combination with cytarabine impaired persistence of AML primary cells within the AML niche. Future therapeutic approaches could involve BMPR1B and/or TAZ/TEAD targeting in the context of AML patients refractory to chemotherapy or after relapse.

P3, N=172, Active, not recruiting, Children's Cancer Group, China | Recruiting --> Active, not recruiting