With the rapid advancement of molecular profiling and precision therapeutics, targeted and immunotherapeutic strategies have irrevocably reshaped the pharmacological management for both nonu2010small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Overall mortality from lung cancer has continued its downward trend over the past decade, and this decline has accelerated, largely driven by advances in early detection and curativeu2010intent surgeries. In parallel, the systemic therapies have undergone a dramatic evolution with the integration of, for example, antibodyu2010drug conjugates (ADCs) and bispecific antibodies (BsAbs). The year 2025 marks a period of significant progress in lung cancer treatment, characterized by groundbreaking therapeutic successes across all disease stages and subtypes. This comprehensive review synthesizes pivotal evidence presented at key oncology forums in 2025 to delineate the substantially evolved clinical landscape.
ABSTRACT As a leading cause of cancer‐related morbidity and mortality worldwide, non‐small cell lung cancer (NSCLC) is profoundly influenced by innate immune cells (IICs). In addition to serving as key mediators of antimicrobial defense and adaptive immune activation, IICs exert pivotal and multifaceted influences on the initiation, progression, and therapeutic responses of NSCLC. This review integrates current knowledge on the classification, phenotypic plasticity, and functions of IICs, as well as their crosstalk within the tumor microenvironment in NSCLC, summarizes therapeutic strategies targeting IICs, and discusses the existing challenges and future perspectives in NSCLC immunotherapy, to provide theoretical references for the immunotherapy of NSCLC.
ABSTRACT When cells are unable to maintain their proper functions, they go into “Cell Death”, either “Accidental” which is uncontrolled, or “Regulated” which is programmed and involves signaling cascades of specific molecules. Any perturbation of the cell death pathways is correlated with a large range of diseases including cancers. These irregularities in cell death mechanisms could however be used as therapeutic targets for a wide range of tumor indications. One of these strategies describes as “Cancer Immunotherapy” is using the power of the immune system to destroy cancer cells. A specific branch of Immunotherapy is “Immunogenic Cell Death” (ICD) which enhances tumor immunogenicity through regulated cancer cell death and triggers tumor‐specific adaptive immune responses. A better understanding of ICD is critical for getting better anti‐cancer modalities. This review focuses on ICD mechanisms, highlights the capacity of drugs to induce ICD, and discusses the importance of combining “ICD‐inducers” with other strategies to enhance their efficiency.
ABSTRACT Gynecologic cancers remain a major global health burden for women. Their management has evolved toward a gynecologic oncologist‐led multimodal paradigm. While these approaches have improved outcomes, critical limitations persist, including challenges in decision‐making during surgical procedures and suboptimal efficacy coupled with frequent resistance and substantial toxicities during medical management. Recent high‐quality clinical trials have helped refine these areas. In early‐stage cervical cancer, sentinel lymph node biopsy has emerged as a safe and effective alternative to systematic lymphadenectomy, preserving oncologic outcomes while minimizing morbidity. In advanced ovarian cancer, primary debulking surgery has been established as superior to neoadjuvant chemotherapy followed by interval debulking surgery in fit patients treated at experienced centers. Meanwhile, immunotherapy demonstrates promise through strategic combinations, including dual checkpoint inhibition and triplet regimens incorporating chemotherapy and anti‐angiogenic agents. Antibody‐drug conjugates (ADCs) directed against folate receptor alpha (FRα) and tissue factor (TF) have shown durable responses in biomarker‐selected populations. By critically synthesizing these advances, this review seeks to delineate the clinical utility of emerging therapies, highlight knowledge gaps, and inform evidence‐based decision‐making for clinicians and researchers.
Breast cancer represents a major threat to women's health in China. Its continuously rising incidence contributes to a growing disease burden, thereby creating a critical demand for novel and effective therapeutic strategies. In recent years, poly ADP-ribose polymerase (PARP) inhibitors, as a novel class of anti-tumor drugs targeting the DNA damage repair pathway, have demonstrated remarkable efficacy in treating breast cancer with BRCA1/2 mutations. By selectively inhibiting DNA repair in tumor cells, these agents induce a "synthetic lethality" effect, offering a new option for precision therapy. Currently, PARP inhibitors such as Olaparib and Fluzoparib have been approved for clinical use. This consensus, based on the latest evidence-based medical data, provides guidance on the standardized application and safety management of PARP inhibitors in breast cancer treatment, aiming to serve as a reference for clinical practice.
ABSTRACT With the rapid advancement of molecular profiling and precision therapeutics, targeted and immunotherapeutic strategies have irrevocably reshaped the pharmacological management for both non‐small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Overall mortality from lung cancer has continued its downward trend over the past decade, and this decline has accelerated, largely driven by advances in early detection and curative‐intent surgeries. In parallel, the systemic therapies have undergone a dramatic evolution with the integration of, for example, antibody‐drug conjugates (ADCs) and bispecific antibodies (BsAbs). The year 2025 marks a period of significant progress in lung cancer treatment, characterized by groundbreaking therapeutic successes across all disease stages and subtypes. This comprehensive review synthesizes pivotal evidence presented at key oncology forums in 2025 to delineate the substantially evolved clinical landscape.
ABSTRACT Background Gastric cancer (GC) is a prevalent malignancy in China, posing significant health challenges. The persistently high tumor incidence and the rising number of tumor survivors may elevate the risk of multiple primary malignancies (MPMs) in GC patients. Methods We conducted a retrospective study involving 11,045 patients diagnosed with gastric adenocarcinoma at National Cancer Center of China between 2010 and 2017. A 6‐month interval distinguished synchronous MPMs (SMPMs) from metachronous MPMs (MMPMs). Results Of all GC patients, 443 (4.01%) had MPM, with 75.85% being males and an average age of 60 at initial diagnosis. Among the MPM cases, 415 (93.68%) had two primary cancers (53.98% synchronous and 46.02% metachronous), 27 (6.09%) had three, and 1 (0.23%) had four, totaling 472 extra gastric cancer sites. Esophageal, colorectal, and lung cancers were the most prevalent concomitant malignancies, with esophageal cancer more frequent in synchronous cases and breast cancer (observed only in females) more frequent in metachronous cases (both p < 0.001). In patients with two primary cancers, the SMPM subset included more males (p < 0.001), with higher rates of smoking (p = 0.012), alcohol consumption (p < 0.001), and higher T stage at first diagnosis (p < 0.001). The MMPM subset included more females (p < 0.001), was younger at first diagnosis (p < 0.001), and more frequently underwent surgery after first diagnosis (p < 0.001). Conclusions MPM occurring in patients with GC predominantly involve the esophagus, colorectum, and lung. Elderly male patients with smoking or alcohol use represent a higher‐risk group and warrant vigilant surveillance. This study provides a clinical and epidemiologic basis for future research on MPM in GC.
Background:Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have become a cornerstone in the first-line management of hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer. Despite their clinical efficacy, most patients eventually experience disease progression, and optimal treatment strategies following CDK4/6 inhibitor resistance remain unclear. Emerging evidence suggests that switching endocrine therapy (ET) while continuing cyclin inhibition may provide additional clinical benefit. Dalpiciclib, a selective CDK4/6 inhibitor, in combination with physician-selected ET, represents a potential option in this setting. Concurrently, 16α-[18F]fluoro-17β-estradiol ([18F]FES) PET/CT, a novel imaging modality targeting estrogen receptors (ER), enables non-invasive, whole-body assessment of ER expression in metastatic lesions, offering a personalized approach to treatment selection. Methods:This is a prospective, single-center, single-arm Phase II clinical trial evaluating the efficacy and safety of dalpiciclib plus ET in HR+/HER2- advanced breast cancer patients who progressed on prior CDK4/6 inhibitor therapy. Forty eligible patients with confirmed metastases and at least one [18F]FES-positive lesion will be enrolled. Participants will receive dalpiciclib combined with ET as determined by the treating physician. The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Discussion:Beyond evaluating efficacy, this single-center phase II trial will provide practical insight into the feasibility of [18F]FES PET/CT-guided patient selection, including standardized imaging workflows and multidisciplinary implementation in routine clinical research. Positive outcomes may support a personalized, imaging-guided strategy to prolong disease control after prior CDK4/6 inhibitor progression. Ethical Approval and Trial Registration:Approved by the Ethics Committee of Peking Union Medical College Hospital (Approval number: K3629); registered at ClinicalTrials. gov (NCT05613270).
ABSTRACT Extensive research continues to address the challenges of developing standard cancer drugs. However, until more effective standard drugs are developed, ferulic acid (FA) may be a potential option for controlling the symptoms of cancer patients. According to our review, FA is available in natural sources and has flexible structures that possess diverse pharmacological activities. FA is effective against 16 different cancer types and has been validated in cell culture, preclinical, and clinical models. Chemotherapeutics activities of FA are regulated through varieties of mechanisms, including targeting signaling pathways, such as AKT/PI3K/mTOR/ERK/STAT NF‐κB; apoptosis, such as FAS/FASL, TRADD, Bcl2, Bax, Caspases, and PARP; metastasis, such as MMPs(1,2,9), Wnt/‐β catenin, angiogenesis (E&N Cadherin, vimentin, Snail, and Slug), cell proliferation (cyclin D1, E1, and CDKs(2,4,6)), inflammatory molecules (TNF‐α, NF‐κB,1α, IL‐10, IL‐8, and IL‐6), regulating tumor suppressor genes (p‐RB, p21, and p53), autophagy (LC3‐II, p62, Beclin1, and Atg12–Atg5), glycolysis (lncRNA 495810 and PKM2), heat shock protein (Hsp60, Hsp70, and Hsp90), and some nonspecific pathways, such as oncogene suppression and antioxidant efficacies. Nanoformulation of FA increased its solubility, stability, and bioavailability, thereby enabling controlled release and making FA more effective against cancer. Additionally, FA exerted synergistic effects with other natural compounds, vitamins, radiotherapy, and chemotherapies, and reversed resistance to existing chemotherapies via diverse mechanisms, including targeting multidrug resistance proteins, apoptosis, reactive oxygen species production, hypoxia, microRNA, the β‐catenin pathway, oncogene activation, and sensitizing chemotherapies and radiotherapies. Given that FA has validated the experimental model and demonstrated preliminary efficacy, these findings suggest a possible supportive role for phytochemicals pending the development of fully effective pharmaceutical therapies.
Human epidermal growth factor receptor 2 (HER2) is a key biomarker and therapeutic target in several malignancies, including breast, gastric, and other solid tumors. Recent advancements in cancer molecular profiling and the Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive pan-tumor indications have highlighted the broader relevance of HER2 alterations across diverse cancers. However, the lack of standardized guidelines for HER2 testing in a pan-tumor context creates variability in clinical practice, hindering the optimal implementation of HER2-targeted therapies beyond traditional indications. To address this gap, a multidisciplinary panel of Chinese experts has developed a consensus providing comprehensive recommendations on diagnostic strategies, testing methodologies, and clinical applications of HER2 overexpression detection. By establishing a unified framework for HER2 overexpression assessment, this consensus aims to enhance the precision of HER2 testing, optimize patient selection for targeted therapies, and improve clinical outcomes across a wide spectrum of HER2 overexpression malignancies.
ABSTRACT Chimeric antigen receptor (CAR) T‐cell therapy has been proved to be an effective cancer immunotherapy strategy against haematological malignancies, but exhaustion, limited persistence, and treatment‐related toxicity have been identified as major roadblocks in solid tumour treatment. Small‐molecular compounds could effectively improve CAR T‐cell therapy, such as preventing exhaustion, enhancing memory formation, and enhancing the antitumor activity. Additionally, adding small molecule switches based on tetracycline‐controlled gene expression system is an effective strategy to improve the safety of CAR T therapy and reduce its side effects. Despite the encouraging preclinical and clinical results, challenges still remain in optimizing dosing regimens and managing drug interactions. This review aims to summarize recent advances in combined approach and to discuss the underlying mechanisms of its potential benefits.
ABSTRACT Background To evaluate the efficacy and safety of novel chemotherapy regimens, including brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs), in children, adolescents, and young adults (CAYA) with Hodgkin lymphoma (HL). Methods A retrospective analysis was conducted on untreated Stage IIB (bulky), III, or IV HL patients (≤ 24 years) who were admitted to Cancer Hospital of the Chinese Academy of Medical Sciences and Beijing Children's Hospital, Capital Medical University, from 2017 to 2024. The cohort compared conventional regimens with BV‑based therapies (BV‑AVD ± R). Furthermore, the efficacy and safety of ICIs were evaluated in relapsed/refractory cHL patients receiving second‑line or later therapy. Results In this comparison between BV and conventional regimens, 182 patients were enrolled. The median follow‐up was 38 months. No significant differences were observed in objective response rate (ORR) (96.4% vs 95.4%, p = 0.927) or progression‐free survival (PFS) rate (92.8% vs 95.3%, p = 0.466).However, the incidence of Grade 4 hematologic toxicity was significantly higher with conventional therapy compared to BV‐AVD±R (61.2% vs 25.6%, p < 0.001). The BV‐AVD group alone achieved a significantly higher ORR than the BV ‐AVD+R group (100% vs. 93.9%, p = 0.047), while there was no significant difference in PFS rate. However, the BV‐AVD + R group exhibited a significantly higher incidence of Grade 3–4 hematologic toxicities (78.8% vs. 20.0%, p = 0.023). Immune checkpoint inhibitors was well‐tolerated with infrequent adverse events, and 18/19 cases (94.7%) demonstrated treatment efficacy. Conclusion For patients with stage II Hodgkin lymphoma presenting with bulky disease, as well as those with stage III–IV disease, the BV‐AVD regimen is recommended as first‐line therapy, given its more favorable toxicity profile.Although ICIs represent a promising therapeutic approach, existing studies are constrained by limited sample sizes. Future research should focus on expanding patient cohorts to refine treatment strategies and ultimately improve clinical outcomes.
Background:To report the global, regional, and national burden of breast cancer (BC) and its attributable risk factors between 1990 and 2021, by age, sex, and sociodemographic index. Methods:Using data from the Global Burden of Disease Study 2021, we analyzed BC prevalence, deaths, disability-adjusted life years (DALYs), and attributable risk factors across 204 countries and territories from 1990 to 2021. Age-standardized prevalence, deaths, and DALYs rates were estimated, and temporal trends were assessed using the estimated annual percentage change. Geographical and sociodemographic inequalities were further evaluated using decomposition analysis, concentration curves, and sociodemographic index (SDI)-based modeling. Attributable risk factors for deaths and DALYs were quantified using the comparative risk assessment framework. Results:Globally, BC presents a starkly diverging landscape. While the age-standardized prevalence has climbed to 239 per 100,000 (a 9.3% increase since 1990), the death and DALYs rates have actually declined by 13.7% and 9.8%, respectively. This global trend, however, masks a critical geographical shift. High-income regions maintain the highest prevalence, yet the most rapid increases in burden are now concentrated in resource-limited areas such as North Africa and the Middle East. The "triple threat" in low-SDI regions defines this transition. Decomposition analysis revealed that while population growth and aging lead to absolute mortality everywhere, high-SDI regions successfully offset this pressure through favorable epidemiological changes and advancements in screening and treatment. In contrast, low-SDI regions face a deteriorating epidemiological profile that actively contributes to rising deaths. Our inequality analysis further underscores this systemic shift; concentration curves confirm that BC mortality is becoming disproportionately concentrated in lower-SDI countries over time. Additionally, the disease follows a nonlinear, inverted U-shaped relationship with socioeconomic development, peaking at an SDI of 0.75. Finally, we identified a distinct sex-based etiological divide: while female risk patterns are multifaceted, male BC is almost singularly driven by metabolic dysregulation, with high body mass index emerging as the leading global driver of the disease. Conclusions:Despite progress in reducing the BC burden, it remains a global public health challenge. The prevalence is high in developed countries, while the burden is rapidly increasing in low- and middle-income countries.
ABSTRACT This review summarizes landmark advances in colorectal cancer treatment in 2025, characterizing the transition to dynamic precision oncology. Immunotherapy has revolutionized mismatch repair‐deficient or microsatellite instability‐high patients, becoming the standard first‐line and perioperative regimen. Precision medicine expanded to patients with BRAF V600E, KRAS mutation, and HER2 amplification. While circulating tumor DNA utility was confirmed for surveillance and guiding rechallenge, its role in real‐time treatment adjustment continues to be explored.
Background:The detection of estrogen receptor 1 (ESR1) ligand-binding domain mutations in circulating tumor DNA (ctDNA) is crucial for guiding therapy in estrogen receptor-positive metastatic breast cancer. However, widespread clinical adoption of approaches for monitoring drug resistance and guiding treatment decisions is hindered by limitations of current methods regarding sensitivity, cost, and multiplexing capability. Methods:The application of switch-blocker technology, which has been patented for detecting ESR1 hotspot mutations (Y537S/C, D538G, E380Q, and L536H/P), suppresses the amplification of wild-type alleles while allowing specific amplification of low-frequency mutant alleles. We used a switch-blocker to inhibit the amplification of a DNA target approximately 10 base pairs in length (e.g., the switch-blocker covering codon 536 of ESR1 targets various variants at positions 536, 537, and 538). Targeted enrichment was achieved by quantitative polymerase chain reaction, followed by pyrosequencing to confirm mutation components. Next-generation sequencing and Sanger sequencing served as supplementary methods for the verification of results. Results:The ESR1-targeted DNA assay was validated for feasibility on plasmid circular templates and ctDNA linear templates. In tests using gradient-diluted ESR1 plasmid templates, the proportion of L536H mutant copies increased from 0.0015% to 16.89% after targeted amplification, while the proportion of E380Q mutant copies increased from 0.0015% to 1.35%. In ctDNA samples previously analyzed by next-generation sequencing, the switch-blocker considerably enriched other mutant copies within the coverage range of the switch element. Conclusions:This switch-blocker-enhanced pyrosequencing assay presents a targeted, multiplexed, and accessible approach for detecting ESR1 hotspot mutations in liquid biopsies. This assay has potential for dynamic monitoring of therapeutic resistance, facilitating timely treatment decisions in advanced breast cancer management.
Background:Sclerosing adenosis (SA) and breast cancer (BC) often exhibit overlapping clinical, imaging, and pathological characteristics, making them difficult to differentiate. SA may also coexist with BC (SA + BC), including ductal carcinoma in situ (SA-DCIS) and invasive breast cancer (SA-IBC), which complicates diagnosis even when core-needle biopsy (CNB) suggests SA. This study aimed to develop interpretable AI-based binary and ternary classification models that leverage clinical and imaging features to distinguish SA-only from SA + BC and to further differentiate among SA-only, SA-DCIS, and SA-IBC. Methods:We retrospectively analyzed a cohort of 726 patients with SA (January 2006 to December 2021), comprising 537 SA-only and 189 SA + BC cases (90 SA-DCIS, 99 SA-IBC). Multiple machine learning algorithms-logistic regression, support vector machine, decision tree, XGBoost, and random forest-were compared using AUC, accuracy, F1-score, and C-index. Model interpretability was assessed with SHAP to elucidate feature contributions and identify key predictors. Additionally, we incorporated an independent external validation cohort consisting of 113 patients to verify the model's effectiveness. Results:XGBoost consistently outperformed other algorithms in both tasks. Eight features emerged as most informative: age, ultrasound BI-RADS category, maximum and minimum ultrasound diameters, ultrasound margin characteristics, biopsy procedure, mammographic density, and microcalcifications. For binary classification (SA-only vs. SA + BC), XGBoost achieved an AUC of 0.925, accuracy of 0.883, and C-index of 0.844. For ternary classification (SA-only, SA-DCIS, SA-IBC), the model achieved an AUC of 0.888, accuracy of 0.811, and C-index of 0.813. Age, ultrasound BI-RADS, and minimum lesion diameter were consistently top predictors. We further proposed a three-tier interpretability framework (global, cohort-level; local, subgroup-level; and individual, case-level) to facilitate clinical translation. Conclusion:Given the substantial risk of coexisting of SA with DCIS or IBC, and the potential for CNB to underestimate disease due to limited sampling, lesions diagnosed as SA on CNB should be evaluated with additional modalities before determining the need for surgical excision. The proposed interpretable AI model enhances discrimination between SA-only and SA with concomitant breast cancer (SA + BC), thereby supporting more informed clinical decision-making in breast disease management.
The convergence of artificial intelligence (AI) and big data is reshaping contemporary oncology by enabling the integration of multimodal information across imaging, pathology, genomics, and clinical records. From a physician-centered perspective, these technologies can potentially be used to improve diagnostic precision, support individualized treatment planning, enhance longitudinal patient management, and accelerate both clinical and translational research. In this review, we synthesize the core AI methodologies most relevant to oncology-machine learning, deep learning, and large language models-and examine how they interact with established and emerging oncology data platforms. We further highlight practical use cases in clinical workflows and research pipelines, emphasizing opportunities for advancing precision cancer care while also addressing challenges associated with data heterogeneity, model generalizability, privacy protection, and real-world implementation. By underscoring the synergistic value of AI and big data, this review aims to inform the development of clinically meaningful, context-adapted strategies that promote translational innovation in both global and locally resourced healthcare environments.
