P2/3, N=345, Active, not recruiting, Pharma Mar S.A. | Recruiting --> Active, not recruiting

While modulating Bcl-2 pathways can be effective in MS, future research should aim to provide greater clarification and to design precision-based drugs capable of neuroprotective effects.

Among 5 255 randomized patients, 374 (7.1%) had LTBI and received preventive treatment, most commonly isoniazid (82.1%) and rifampicin (11.8%). From Year 1-5 (after ~98% of LTBI+ patients completed preventive treatment), transaminase elevations were generally similar among LTBI+ and LTBI- patients. The absence of observed TB risk in guselkumab-treated patients suggests IL-23 inhibitors may be better treatment options than TNFi in high-risk patients, including those in TB-endemic regions.

From approval of immune checkpoint inhibitors and lurbinectedin, a newer chemotherapy agent, to novel immunotherapies such as tarlatamab, a DLL3-CD3 bispecific T-cell engager, and other upcoming promising drugs, the therapeutic armamentarium for SCLC is steadily expanding. In this study, we review the current landscape of both systemic therapy as well as radiation therapy for SCLC, with a focus on major developments over the past decade, current standards of care, and novel therapeutics that are expected to revolutionize the treatment of this aggressive malignancy.

Only inhibition of CDK9 (by AZD4573 and atuveciclib) or of CDK12/13 (by SR4835 and THZ531)-which target the transcriptional elongation of RNA polymerase II (RNAPII)-exerted a strong apoptotic potential. Because Bcl-2 only inhibits Bax, but not Bak, AZD4573 and SR4835 were able to induce apoptosis in Jurkat cells overexpressing Bcl-2. As tumor cells frequently upregulate Bcl-2, inhibitors of CDK9 and CDK12/13 represent promising anticancer drugs.

Silibinin and sodium oxamate, as HIF-1α and LDHA blockers, respectively, were used to treat K-562 and HL-60 cells...In contrast, PD-L1 expression remained unchanged after treatment. Our findings suggest that blocking signaling pathways involved in metabolic reprogramming of cancer cells could be a promising approach for modulating the expression of certain immune checkpoint ligands, warranting further investigation.

P3, N=455, Active, not recruiting, PharmaMar | Recruiting --> Active, not recruiting

P3, N=705, Completed, PharmaMar | Active, not recruiting --> Completed

Structure-based screening identified silibinin and estradiol benzoate as LRP1-specific agonists that activate the WTAP-LRP1 pathway to promote cartilage repair in vivo. Collectively, our findings establish m6A-dependent metabolic reprogramming as a pivotal epigenetic mechanism of cartilage regeneration with therapeutic potential for promoting chondrogenesis.

We present a case of a 66-year-old female with de novo metastatic NSCLC harboring an EGFR mutation, RET rearrangement, and ERBB2 amplification, who experienced transformation to SCLC while on osimertinib. Subsequently, she exhibited primary refractory disease to both first-line platinum doublet with immunotherapy and second-line lurbinectedin...The patient had minimal side effects and obtained a partial response with a progression-free survival (PFS) of 13.1 months, better than historically poor prognosis seen in transformed SCLC. This case underscores the potential role of human epidermal growth factor receptor 2 (HER-2) directed therapies, such as T-DXd, in transformed SCLC.

P2, N=30, Not yet recruiting, Sichuan University | Initiation date: Dec 2025 --> Oct 2026

In summary, this study demonstrates that SM-mediated targeting of UCP2 enhances hepatic mitochondrial function and suppresses excessive mitophagy, thereby ameliorating TBil in TAA-induced HE. These findings suggest that SM may represent a promising therapeutic strategy for TAA-induced HE.