Solanum lyratum Thunb is a traditional Chinese medicinal with a significant clinical outcome for tumor treatment; however, chemicals or fractions separated from the herb did not exhibit strong and comparable efficacy. To investigate the potential synergy or antagonism among chemicals in the extract, we obtained the compounds solavetivone (SO), tigogenin (TI) and friedelin (FR) from the herb. The anti-tumor effects of these three monomer compounds alone or in combination with the anti-inflammatory compound DRG were also tested in this study. SO, FR and TI used alone did not inhibit the proliferation of A549 and HepG2 cells, but the combination of the three achieved 40% inhibition. In vitro anti-inflammatory analysis showed that DRG had a stronger anti-inflammatory effect than TS at the same concentration, and the combination of DRG with SO, FR or TI inhibited the anti-tumor effect of DRG. This is the first study that documented the synergistic and antagonistic interactions between different compounds in a single herb. Graphical Abstract

YEATS2, an evolutionarily conserved reader of histone acylation marks (H3K27ac, H3K27cr, H3K27bz), functions as a central oncogenic driver in diverse cancers, including non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC). Its structurally plastic YEATS domain bridges acyl-CoA metabolism to chromatin remodeling, amplifying transcription of survival genes such as MYC, BCL2, and PD-L1. YEATS2 orchestrates malignancy-specific programs—sustaining ribosome biogenesis in NSCLC through ATAC complex recruitment, enhancing NF-κB-dependent immune evasion in PDAC, and activating PI3K/AKT-driven metabolic rewiring in HCC. Structural studies demonstrate a unique aromatic cage architecture that selectively engages diverse acylated histones. Although pyrazolopyridine-based inhibitors targeting the YEATS domain show preclinical efficacy, developing isoform-selective agents remains challenging. Clinically, YEATS2 overexpression correlates with therapy resistance and may synergize with immune checkpoint blockade. This review integrates mechanistic insights into the role of YEATS2 in epigenetic regulation, evaluates its therapeutic potential, and proposes future directions: elucidating full-length complex topologies, mapping synthetic lethal interactors, and optimizing selective inhibitors. Disrupting YEATS2-mediated epigenetic adaptation presents novel opportunities for precision cancer therapy.

Background: The conventional approach for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC) entails the combination of surgery with radiotherapy or chemoradiotherapy. However, the survival rate of patients has not improved. This is frequently attributed to the strong invasive and metastatic capabilities of the tumor, which makes it prone to recurrence. In recent years, neoadjuvant chemoimmunotherapy has emerged as a focal point of research. This is primarily due to its remarkable enhancement of the pathological response rate and patient survival. The objective of this study was to conduct a retrospective analysis to evaluate the safety and efficacy of neoadjuvant chemoimmunotherapy in locally advanced HNSCC.Methods: The clinical data of 82 patients with HNSCC, who underwent surgery subsequent to neoadjuvant chemoimmunotherapy during the period from January 1, 2019, to May 31, 2024, were retrospectively incorporated in this study. Analyses were conducted on the pathological response rate, survival data, and adverse events associated with the treatment.Results: This study enrolled 82 patients in total. The oral cavity was the site of malignancies in 41, 50.0% of the cases. Nearly half of the patients (32, 39.0%) were treated with two cycles of neoadjuvant chemoimmunotherapy, while the remaining patients received three or more cycles. 78 patients (95.1%) achieved R0 resection and 65 patients (79.3%) achieved objective response rate (ORR). The pathological complete response (pCR) rate was 25.6% [95% confidence interval (CI), 15.3%–35.1%], and the major pathological response (MPR) rate was 41.5% (95% CI, 30.4%-52.0%). All patients demonstrated good tolerance of neoadjuvant therapy, with a grade 3/4 treatment-related adverse event rate of 14.6%. After a median follow-up of 16 (3–48) months, the 1-year disease-free survival rate was 80.5% (95%CI: 72.4%- 88.6%) and the 1-year overall survival rate was 93.7% (95%CI: 88.7%-99.14%).Conclusions: Neoadjuvant chemoimmunotherapy significantly improves the pathological response rate and R0 resection rate in patients with locally advanced HNSCC with a low incidence of treatment-related adverse events, and our findings suggest its potential as a treatment strategy for locally advanced HNSCC.

Background: Locally advanced thyroid cancer is a kind of aggressive malignancy with poor overall survival (OS). Neoadjuvant therapy has shown a certain efficacy in locally advanced thyroid cancer. The objective of this study was to assess the efficacy and feasibility of surgery following neoadjuvant therapy in patients.Methods: In a retrospective study, we analyzed sixteen patients with locally advanced thyroid cancer from January 2019 to June 2024 in our institution. Among them, 7 patients with unresectable differentiated thyroid cancer (DTC) received tyrosine kinase inhibitors (TKI), and 2 patients with poorly differentiated thyroid cancer (PDTC) and 7 patients with anaplastic thyroid carcinoma (ATC) received a combination therapy of TKI, immune checkpoint inhibitors (ICI) or chemotherapy. Response and progression were evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). OS was calculated using the Kaplan-Meier method.Results: 16 (4 male and 12 female) patients with locally advanced thyroid cancer were enrolled in this study, in which 10 patients (62.5%) accepted surgery following neoadjuvant therapy and 6 patients (37.5%) refused surgery. The objective response rate (ORR) was 50.00%, and disease control rate (DCR) was 81.25%. Two partial response (PR), two stable disease (SD) and one progressive disease (PD) patients achieved R0/1 resections after neoadjuvant treatment, resulting in a R0/1 resection rate of 50.00%. Grade III/IV toxicities developed in 2 of 16 patients, requiring dose reduction/discontinuation of TKI. The median OS was 17 months, with one PDTC, four ATC and six DTC patients still alive without relapse.Conclusions: Neoadjuvant treatment, including TKI, ICI or chemotherapy treatment, was safe and effective in locally advanced thyroid cancers and could create radical surgery opportunities to improve the prognosis of patients.