Hengshui University

Abstract Background: Dalpiciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has shown significant efficacy and a favorable safety profile when combined with endocrine therapy for advanced hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Building on this evidence, the present study evaluated the efficacy and safety of neoadjuvant dalpiciclib plus letrozole compared with standard chemotherapy in patients with high-risk HR+/HER2- early breast cancer. Methods: DARLING-02 was a multicenter, randomized, phase II non-inferiority trial (NCT06107673). Key eligibility criteria included women aged ≥18 years; Eastern Cooperative Oncology Group performance status 0-1; clinical stage T1c-2N1-2 or T3-4N0-2; estrogen receptor (ER) expression ≥50%; HER2- status; and Ki-67 level ≤30%. Patients were randomized 1:1 to receive 24-week treatment. The experimental arm received dalpiciclib 150 mg orally once daily (3 weeks on, 1 week off) plus letrozole 2.5 mg orally once daily. The control arm received epirubicin 100 mg/m2 plus cyclophosphamide 500 mg/m2 intravenously on day 1 every 3 weeks for 4 cycles, followed by docetaxel 100 mg/m2 intravenously on day 1 every 3 weeks for 4 cycles. The primary endpoint was objective response rate (ORR), assessed per Response Evaluation Criteria in Solid Tumors, version 1.1. Results: Between August 2023 and April 2025, 170 patients were screened; 158 met the eligibility criteria and were randomized to the dalpiciclib-letrozole (n = 80) or chemotherapy (n = 78) group. At the data cut-off date (September 17, 2025), 9 patients in the experimental arm and 10 in the control arm were still on neoadjuvant therapy. Among patients with completed short-term efficacy assessment, the ORR was 69.0% (49/71) with dalpiciclib-letrozole and 70.5% (48/68) with chemotherapy; total pathological complete response (tpCR) rate was 5.6% (4/71) and 1.5% (1/68), respectively. The proportion of patients with Preoperative Endocrine Prognostic Index (PEPI) score ≥4 was higher in the chemotherapy group (74.6% [44/59]) than in the dalpiciclib-letrozole group (53.3% [32/60]). Grade ≥3 adverse events were predominantly hematological toxicities and occurred less frequently with dalpiciclib-letrozole than with chemotherapy (decreased white blood cell count: 36.4% [28/77] vs 64.0% [39/61]; decreased neutrophil count: 74.0% [57/77] vs 86.9% [53/61]). Conclusions: These findings support dalpiciclib plus letrozole as a promising neoadjuvant option for patients with high-risk HR+/HER2- early breast cancer and warrant confirmation in phase III trials. Citation Format: C. Geng, L. Zhang, C. Yang, T. Zhou, L. Ma, R. Luo, Z. Song, Y. Qi, J. Yang, X. Wang, J. Han, J. Ma, Z. Zhang, Y. Li, C. Gao, L. Yang, J. Yu. Neoadjuvant Dalpiciclib Plus Letrozole Versus Standard Chemotherapy in High-Risk HR+/HER2- Negative Breast Cancer (DARLING-02): A Randomized Phase II Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-13-08.

The genus Australobius Chamberlin, 1920 is a small genus of subfamily Lithobiinae Newport, 1844 within family Lithobiidae Newport, 1844. The World Catalogue of Centipedes currently records 35 species or subspecies for Australobius. A new species Australobius septforaminis sp. nov., is described based on both sexes (four males and two females specimens) from Guanshan, Yintiaoling National Nature Reserve, Wuxi County, Chongqing, China. A detailed morphological description and illustrations of Australobius septforaminis sp. nov. are provided.

BackgroundProstate cancer (PCa) is the most common male reproductive malignancy, with traditional Chinese medicine (TCM) offering potential complementary treatments. Aidi injection, used for liver, lung, and colorectal cancers, shows promise for PCa, but its mechanisms are unclear. This study aims to uncover the molecular pathways through which Aidi injection affects PCa using network pharmacology and experiments.MethodsThe study used network pharmacology to identify active components of Aidi injection and their targets from various databases. These targets were cross-referenced with PCa-related targets to uncover therapeutic possibilities. Protein-protein interaction (PPI) and KEGG pathway analyses highlighted key molecular pathways affected by Aidi injection. Molecular docking examined ingredient-target binding. In vitro tests evaluated effects on PCa cell proliferation, apoptosis, and IL-6/STAT3 signaling, while in vivo studies assessed tumor growth and immune response in mice.ResultsThe study identified 58 active components and 804 PCa-related target genes, with 49 overlapping therapeutic targets. Key compounds such as quercetin, kaempferol, isorhamnetin, and cantharidin were highlighted. Core targets included ESR1, IL-6, STAT3, HSP90AA1, EGFR, and VEGFA. KEGG analysis revealed the IL-6/STAT3 and EGFR pathways as significant in PCa treatment. In vitro, Aidi injection inhibited PCa cell proliferation, induced apoptosis, and suppressed IL-6/STAT3 activation. In vivo, Aidi injection reduced tumor growth and enhanced immune response in mice.ConclusionsAidi injection influences the IL-6/STAT3 and EGFR pathways, suppressing PCa cell growth, inducing apoptosis, and reducing migration and invasion. These findings offer valuable insights into the therapeutic potential of Aidi injection for prostate cancer.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12575-025-00299-w.