etoposide IV

Moreover, we confirmed that PAF1c deficiency increases the cytotoxicity of several DNA-damaging agents, including hydroxyurea (HU), cisplatin (CDDP), methyl methanesulfonate (MMS), and bleomycin (BLM). Unexpectedly, PAF1c depletion confers tolerance specifically to topoisomerase inhibitors, such as camptothecin (CPT), etoposide (ETOP), and doxorubicin (DOX)...Collectively, our findings demonstrate that loss of PAF1c subunits not only promotes genomic instability through R-loop accumulation but also alters cellular responses to DNA-damaging agents, conferring resistance particularly to topoisomerase inhibitors. This study underscores the critical role of PAF1c in maintaining genome stability and provides a rationale for developing new therapeutic strategies in cancer treatment.

SCLC therapy has shifted from uniform cytotoxic treatment to a tiered, mechanism-driven algorithm that incorporates PD-L1 blockade, targeted cytotoxics, myeloprotection and refined radiotherapy, raising long-term survival above 20% in selected populations. From a European-practice perspective, current best practice is platinum-etoposide plus a PD-L1 inhibitor for treatment-naïve ES-SCLC, thoracic consolidation radiotherapy in selected responders, lurbinectedin or DLL3-directed clinical trials at relapse, and durvalumab consolidation after chemoradiation in LS-SCLC. Outstanding challenges include a low absolute survival gain from chemo-IO, the absence of validated predictive biomarkers, lineage plasticity, and unequal global access to new agents.

The TMEp phase integrated stereotactic body radiotherapy (SBRT), low-dose etoposide, and anlotinib, followed by CI with the programmed death 1 (PD-1)/cytotoxic T lymphocyte antigen 4 (CTLA-4) bispecific antibody cadonilimab and concurrent probiotic supplementation...The TMEp-CI-M platform may enhance the efficacy of immunotherapy in ES-SCLC, enabling durable responses even in patients with brainstem metastases. Although this platform has demonstrated promise across multiple tumor types, further prospective and mechanistic studies are warranted to confirm its clinical utility.

P1/2, N=156, Completed, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2

Specifically, the patient underwent six cycles of induction therapy with the etoposide plus cisplatin regimen combined with sintilimab, followed by intensity-modulated radiation therapy (pGTV 48 Gy, pCTV 48 Gy), and subsequently received maintenance sintilimab monotherapy. For this highly aggressive SMARCA4-deficient tumor, the sequential treatment strategy of "induction chemotherapy-immunotherapy followed by consolidative radiotherapy" enables long-term disease control, and immunotherapy maintenance also demonstrated significant value in delaying disease progression. The experience from this case could inform the diagnostic and therapeutic approach for this rare subtype of lung cancer.

P2, N=37, Suspended, David Bond, MD | Recruiting --> Suspended

This single-arm phase II trial enrolled patients with EPSCC to investigate the activity of first-line durvalumab (1500 mg every 3 wk) and 4 to 6 cycles of chemotherapy (either cisplatin or carboplatin) with etoposide, followed by maintenance durvalumab 1500 mg every 4 weeks until disease progression. This study reveals that durvalumab plus chemotherapy is safe and has some activity in rare small cell cancers outside the lung, but benefits are modest and short lived. Current treatment remains largely chemotherapy based, highlighting the urgent need for larger, collaborative research efforts to find more effective options for these patients.

The patient received eight cycles of alternating VDC/IE (vincristine, doxorubicin, cyclophosphamide / ifosfamide, etoposide) chemotherapy, resulting in a significant reduction in the primary tumor and resolution of the IVC thrombus and skeletal metastases. This case underscores the utility of a multimodal approach, where neoadjuvant chemotherapy can effectively downstage even metastatic disease, facilitating surgical resection. However, the overall prognosis remains poor, particularly for metastatic presentations, highlighting the urgent need for more effective and less toxic therapeutic regimens.

P1, N=48, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

P3, N=306, Completed, GWT-TUD GmbH | Active, not recruiting --> Completed

For example, a recent study in Communications Medicine has demonstrated that histone deacetylase inhibitors de-repress transcription of a tumor suppressor GSDME in B-cell lymphoma cells, and synergize with cisplatin and etoposide to promote GSDME cleavage by caspase-3 and subsequent pyroptosis of lymphoma cells. Furthermore, the anti-lymphoma efficacy of this combination therapy in vivo depends on CD8 T cells. This article provides a brief introduction of the pyroptosis pathway in cancer, comments on this promising 'One action, two benefits' therapeutic strategy for cancer treatment, and discusses the significance and unaddressed questions in recent therapeutic studies targeting pyroptosis-suppressing mechanisms in cancer.

P1, N=55, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting