cytarabine

P3, N=40, Active, not recruiting, Fujian Medical University Union Hospital

P2, N=20, Not yet recruiting, Zhejiang Cancer Hospital

P1, N=36, Recruiting, Children's Oncology Group | Trial completion date: Jun 2026 --> Mar 2028 | Trial primary completion date: Jun 2026 --> Mar 2028

P3, N=700, Active, not recruiting, University of Birmingham | Recruiting --> Active, not recruiting

We identified cytarabine and methotrexate as significantly more effective in the 9p21 compromised BLCA cells. Analysis of morphological alterations further supported a genotype-specific activity of nucleoside analogs, nominating gemcitabine as a drug with greater efficacy in this context...Synergy between cytarabine and inhibitors of PRMT5 (MRTX1719) and MAT2A (AG-270) was mediated by a differential activation of DNA damage and replication stress markers, suggesting an exploitable vulnerability. In fact, rational drug combinations with ATR/CHK1 pathway inhibitors increased efficacy while maintaining 9p21-specificity. Finally, we confirmed the effectiveness of these combinations in cell models of pancreatic adenocarcinoma and pleural mesothelioma, two tumor types with high prevalence of MTAP loss and, most notably, in bladder cancer patient-derived organoids, underscoring the strong translational potential of our findings.

Functionally, MV4-11QR cells showed broad cross-resistance to clinically relevant agents, including midostaurin, venetoclax, and cytarabine. Importantly, pharmacological targeting of mutant p53 with eprenetapopt or MAPK signaling with trametinib restored sensitivity to quizartinib, inducing synergistic or additive cytotoxic effects and increased apoptosis. Together, these findings define a multilayered resistance program involving genetic, signaling, and metabolic adaptations and support rational combination strategies to overcome FLT3 inhibitor resistance in AML.

Pharmacologic AC inhibition with the ceramide analog SACLAC enhanced single-agent venetoclax cytotoxicity and the venetoclax + cytarabine combination in AML cell lines with primary or acquired venetoclax resistance. Importantly, AC knockdown sensitized AML cells to venetoclax and induced NOXA protein accumulation, whereas NOXA knockdown protected against AC and BCL-2 cotargeting. Collectively, these findings demonstrate the efficacy of cotargeting AC and BCL-2, and rationalize targeting AC as a therapeutic approach for venetoclax-sensitive and -resistant AML.

P2/3, N=232, Enrolling by invitation, Guangdong Second Provincial General Hospital

P1/2, N=62, Recruiting, University of Washington | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Dec 2026 --> Dec 2027

The patient initially received 2 cycles of rituximab combined with high-dose methotrexate chemotherapy...Subsequently, the regimen was adjusted to 6 cycles of cytarabine combined with temozolomide chemotherapy followed by radiotherapy for the intracranial lesion...Up to the date of follow-up, the patient's condition was stable without recurrence. Combined with literature review, this article discusses the possible mechanisms of the coexistence of dual-subtype DLBCL (clonal evolution or biclonal origin), the potential pathways of temporal muscle metastasis and the impact of subtype differences on treatment response, which provides clinical reference for the diagnosis and individualized treatment of such rare cases.

P2/3, N=25, Recruiting, Medical University Of Lodz | Not yet recruiting --> Recruiting

P2/3, N=1124, Active, not recruiting, St. Anna Childrens Cancer Research Institute GmbH | Not yet recruiting --> Active, not recruiting