Yunxiang Zhou

Background: Adjuvant CDK4/6 inhibitors improve outcomes in hormone receptor‐positive, HER2‐negative (HR+/HER2−) early breast cancer, yet some patients still experience recurrence. Early relapse in particular is associated with poor prognosis, but the timing and patterns of recurrence following this treatment remain undefined, limiting further therapeutic strategy development. Materials and Methods: We analyzed pivotal trials of adjuvant CDK4/6 inhibitors in early‐stage HR+/HER2− breast cancer to assess the temporal distribution of iDFS events. Invasive disease‐free survival (iDFS) and overall survival (OS) data were extracted from Kaplan–Meier curves using PlotDigitizer. Events were evaluated up to 60 months, a time frame with consistent follow‐up across trials. The primary endpoint was the proportion of early versus total iDFS events and deaths by 60 months. The types and patterns of first iDFS event, as well as adverse events, were also discussed. Results: The 5‐year iDFS in CDK4/6 inhibitor‐containing arms were as follows: 85.5% (NATALEE), 83.1% (monarchE), 84.2% (PALLAS), 67.9% (PENELOPE‐B). Early relapse‐related events (≤ 36 months) accounted for 63.5%, 63.9%, 62.7%, and 60.8% of total iDFS events, respectively, all proportions broadly similar to those observed in the control arms. The temporal distribution of iDFS event rates within consecutive 6‐month intervals appeared generally consistent. Distant metastasis constituted the predominant form of the first iDFS event, with bone as the most common metastatic site. The most frequently reported adverse events included neutropenia and diarrhea. Diarrhea was more prevalent with abemaciclib, whereas neutropenia occurred more frequently with palbociclib. Conclusion: Adjuvant CDK4/6 inhibitors (ribociclib and abemaciclib) demonstrated iDFS benefits in monarchE and NATALEE. In our exploratory analysis, the temporal distribution of iDFS events appeared broadly consistent across trials, with no obvious concentration in any specific period. Given that early iDFS events (≤ 36 months) accounted for a substantial proportion of all events, further prospective studies are needed to optimize treatment for this high‐risk population.

Background:Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide; thus, understanding its molecular mechanisms is critical for developing novel therapeutic targets. Long non-coding RNAs (lncRNAs) play crucial isoform-specific roles in cancer. While oncogenic lncRNA LINC00673 is known to be involved in multiple malignancies and possesses five distinct transcript variants, the functional role of LINC00673-V4—a highly expressed transcript variant in CRC—remains largely unexplored. This study investigated how LINC00673-V4 drives CRC proliferation by modulating the Hippo-Yes-associated protein (Hippo-YAP) signaling pathway.Methods:Survival analysis was performed using the GSE39582 dataset to assess the prognostic value of LINC00673 in patients with CRC. The expression of LINC00673 transcript variants in CRC cell lines was detected by quantitative PCR. Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays were used to assess cell proliferation upon LINC00673-V4 knockdown or overexpression. Western blotting and immunofluorescence staining were utilized to analyze the expression of Hippo-YAP target genes. To confirm the interaction between LINC00673-V4 and fused in sarcoma (FUS), RNA immunoprecipitation (RIP) was performed, while co-IP was used to investigate potential protein–protein interactions.Results:High LINC00673 expression was observed in CRC cell lines and was associated with a poor prognosis in patients with CRC. Among the five LINC00673 transcript variants, LINC00673-V3 and LINC00673-V4 were the predominantly expressed isoforms; however, only LINC00673-V4 significantly promoted CRC cell proliferation. LINC00673-V4 inhibited YAP phosphorylation at Ser127, promoted YAP nuclear translocation, and upregulated the expression of Hippo-YAP target genes (connective tissue growth factor, cysteine-rich angiogenic inducer 61, survivin). RIP assays confirmed an association between LINC00673-V4 and FUS, while co-immunoprecipitation (co-IP) assays revealed that FUS interacted with both YAP and large tumor suppressor 1 (LATS1), suggesting FUS may facilitate LATS1-mediated YAP phosphorylation. FUS was found to promote LATS1-mediated YAP Ser127 phosphorylation, induce YAP cytoplasmic retention, and down-regulate Hippo-YAP target gene expression. Rescue experiments showed that LINC00673-V4 reversed the FUS-induced suppression of Hippo-YAP target gene expression.Conclusions:Our study identified LINC00673-V4 as an isoform-specific oncogenic lncRNA in CRC. By associating with FUS, LINC00673-V4 sequesters FUS away from the LATS1/YAP complex; thereby inhibiting FUS-mediated YAP phosphorylation and enhancing Hippo-YAP target gene expression. These findings expand the landscape of lncRNA isoform-specific regulation in cancer, highlighting LINC00673-V4 as a potential prognostic biomarker and therapeutic target for CRC.

Background: CDK4/6 inhibitors combined with endocrine therapy constitute the global first-line standard of care for HR + /HER2 − advanced breast cancer (ABC), yet no head-to-head trials comparing different CDK4/6 inhibitors have been conducted, and real-world comparative data in Chinese patients is currently unavailable. Methods: We conducted a multicenter retrospective study of 341 Chinese patients with HR + /HER2 − ABC who received first-line palbociclib ( n = 177), abemaciclib ( n = 114), or dalpiciclib ( n = 50) from 2018 to 2023. The primary endpoint was progression-free survival (PFS); secondary endpoints included safety, tolerability, and objective response rate. Results: Median PFS was 24 months for palbociclib and 32 months for abemaciclib, while median PFS for dalpiciclib was not reached. Abemaciclib significantly prolonged PFS compared with palbociclib (palbociclib vs. abemaciclib: adjusted HR = 1.86, 95% CI 1.24–2.79), with consistent benefits in premenopausal, postoperative recurrence, progesterone receptor–positive, HER2-low, luminal B, visceral metastasis, and endocrine-resistant subgroups (all p < 0.05). Overall tolerability was comparable, though palbociclib and dalpiciclib were associated with higher myelosuppression, whereas abemaciclib more frequently caused low-grade diarrhea. Conclusions: This is the larger real-world study to compare different CDK4/6 inhibitors in Chinese HR + /HER2 − ABC patients. Abemaciclib demonstrated a significant PFS advantage over palbociclib while maintaining a manageable safety profile, particularly benefiting biologically aggressive or treatment-resistant subgroups. These findings provide population-specific evidence to guide individualized CDK4/6 inhibitor selection and refine first-line treatment strategies for Chinese patients with HR + /HER2 − ABC.

Triple-negative breast cancer (TNBC) is a highly immunogenic breast cancer subtype, rendering it particularly amenable to immunotherapy. Immune checkpoint inhibitors (ICIs), primarily targeting the PD-1/PD-L1 axis, have transformed the therapeutic landscape of early-stage TNBC, with KEYNOTE-522 trial establishing neoadjuvant pembrolizumab (continued as adjuvant) plus chemotherapy as the current standard of care. However, the substantial toxicity associated with the KEYNOTE-522 regimen, together with residual uncertainty regarding the relative contributions of neoadjuvant versus adjuvant pembrolizumab administration, underscores the need to optimize treatment intensity and refine ICI strategies. Herein, we provide an overview of immunotherapy and its clinical applications in TNBC. We integrate evidence from neoadjuvant and adjuvant ICI trials with mechanistic insights into the biologically optimal timing of immunotherapy. We further highlight emerging strategies aimed at optimizing the current standard-of-care regimen, with the potential to refine treatment timing, duration, dose, combination strategies, and patient selection for ICI therapy, thereby providing insights into future therapeutic approaches for early-stage TNBC.

Understanding the functions and regulatory mechanisms of the epitranscriptome entails robust and accurate analytical methods to identify and quantify post-transcriptional modifications in RNA. However, there are still various challenges in analyzing multiple modified nucleosides in RNA. Herein, we established a highly sensitive and high-throughput hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method, in conjunction with a stable isotope-dilution technique, for accurate quantification of 35 nucleosides. By the use of malic acid as a mobile phase additive, the HILIC-based separation of nucleosides was improved and the MS signal response of nucleosides was enhanced by 2.5- to 20.0-fold. Notably, seven groups of isomeric nucleosides with identical multiple-reaction monitoring ion transitions and six groups of nucleosides with identical or similar molecular weights that were indistinguishable by MS were well resolved by optimal HILIC separation. Thirty-five nucleosides were analyzed simultaneously within 12.5 min, and the limits of detection of these nucleosides ranged from 15.0 amol to 43.5 fmol. With this method, we conducted a comprehensive analysis and evaluation of the alteration in the RNA modification profile in breast cancer and assessed the RNA modification patterns across different breast cancer subtypes. The developed HILIC-MS/MS method has excellent capabilities for sensitive and high-throughput detection of multiple modified nucleosides, thereby providing a valuable analytical tool for deciphering the epitranscriptomic landscape and screening nucleosides as biomarkers in future clinical research.

Phyllodes tumors of the breast are rare fibroepithelial neoplasms accounting for less than 1% of breast tumors, with malignant phyllodes tumors (MPTs) representing approximately one-quarter of cases. Occurrence during pregnancy is exceedingly uncommon and may be associated with accelerated tumor growth. We report a 32-year-old woman at 15 weeks of gestation with a two-year history of recurrent MPT who had undergone four prior excisions. During the current pregnancy, the tumor recurred with rapid progression and rib invasion. After multidisciplinary evaluation, radical extended resection with chest wall reconstruction using the latissimus dorsi muscle was performed in the second trimester without perioperative complications. The pregnancy continued uneventfully, and a healthy full-term infant was delivered. At six-month follow-up, no local recurrence or metastasis was detected. Herein, we present the first documented case of complete resection of a rib-infiltrating MPT during pregnancy and provide a comprehensive synthesis of the existing literature to inform the characteristics and comprehensive management of MPTs, with particular emphasis on surgical strategies. We also summarize available evidence on pregnancy-associated MPTs to characterize their clinical and biological features. These insights may inform individualized treatment planning and optimize the overall management of these rare tumors.

Triple-negative breast cancer (TNBC) remains a therapeutic challenge due to its aggressive nature and lack of ER, PR and HER2 expression. Recent advances, however, are reshaping its treatment landscape, particularly with antibody-drug conjugates (ADCs) and immunotherapies. ADCs such as sacituzumab govitecan and datopotamab deruxtecan have demonstrated superior efficacy over standard chemotherapy in metastatic TNBC. Furthermore, combining these ADCs with immune checkpoint inhibitors is emerging as a powerful strategy to enhance antitumor activity, as evidenced by encouraging results from trials like MORPHEUS-panBC and BEGONIA. While most evidence currently centers on metastatic disease, these novel combinations are also being rapidly evaluated in neoadjuvant and adjuvant settings. Given this rapid progress, this article aims to summarize recent advances in ADCs and immunotherapy combinations for TNBC, discuss their synergistic mechanisms, and provide insights for future personalized therapeutic strategies.

Traditional cancer research models face inherent limitations: two-dimensional (2D) cell cultures fail to capture the complexity of tumor biology, whereas animal models are confounded by species-specific discrepancies. The integration of tumor organoids with three-dimensional (3D) bioprinting has recently emerged as a transformative strategy. This approach combines the histological and genetic fidelity of organoids with the spatial precision and structural controllability of 3D bioprinting, thereby enabling the fabrication of biomimetic tumor models. Such models more faithfully recapitulate critical features of the tumor microenvironment (TME), addressing major gaps in conventional experimental systems. This review systematically examines the principles, recent advances, and translational applications of 3D bioprinting-enabled tumor organoids, including the biological basis of organoids, key bioprinting strategies, and technical considerations. Major applications involve constructing heterogeneous TMEs with immune interactions, engineering vascularized tumor structures, enabling high-throughput drug screening, validating bioprinted organoids in clinical samples, and advancing the clinical translation, regulatory frameworks, and Good Manufacturing Practice (GMP) compliance of tumor organoids. Despite substantial progress, several challenges remain, including limited printing resolution, instability of bioinks, difficulties in sustaining long-term culture, and standardization gaps. Nevertheless, integration with emerging technologies such as microfluidics, artificial intelligence (AI), big data analytics, and standardized biomanufacturing platforms is anticipated to bridge basic tumor research with clinical translation. Ultimately, these synergistic advances may accelerate the development of personalized cancer therapies and improve patient outcomes.