Volume 03 · Issue 02 · 2025

乳腺癌是最普遍的女性恶性肿瘤，严重威胁受影响个体的健康。¹乳腺癌分子亚型鉴定的最新进展确保了更个性化和精确的治疗策略。²这在治疗方案和疾病预后方面提出了新的挑战和机遇。本期特刊名为"乳腺癌研究最新进展》，重点介绍了乳腺癌临床、基础和转化研究的最新进展。它探索了肿瘤耐药机制和微环境，以增强我们对药物疗效和安全性的理解。

由于与中枢神经系统相关的复杂性，建立研究和评估模型在脑肿瘤研究领域提出了挑战。这极大地阻碍了脑肿瘤治疗方法的发展。¹为了使我们能够理解肿瘤细胞及其微环境之间的复杂相互作用，并在脑肿瘤研究方面取得重大进展，该杂志特刊“了解脑肿瘤的进展以及临床和转化研究的前景”中的三篇最近出版物集中于阐明诊断模式和完善细胞和动物模型。^2,3,4这些贡献为研究脑肿瘤和脑转移提供了不同的途径。

Platinum-based chemotherapy, a cornerstone in the treatment of various malignancies, is often limited by its potential cardiotoxic effects. Understanding these effects is crucial for optimizing patient outcomes and guiding treatment decisions. This review explores the mechanisms, clinical manifestations, detection, management, and future directions in the research of cardiotoxicity associated with platinum-based chemotherapy. The mechanisms discussed here include oxidative stress, reactive oxygen species production, DNA damage, and alterations in signaling pathways. Clinical manifestations range from mild symptoms to severe complications, including Takotsubo cardiomyopathy, as highlighted by recent case studies. The role of diagnostic tools such as echocardiography, cardiac magnetic resonance imaging, and cardiac biomarkers in early detection is emphasized, underscoring the importance of regular cardiac monitoring. Management strategies focus on cardioprotective agents, alternative chemotherapy regimens, and emerging therapeutic approaches, including the potential of nano liposomal and cubosomal formulations. The review also delves into the future of personalized medicine in predicting and managing cardiotoxicity, advocating for ongoing research to mitigate these adverse effects. This comprehensive overview aims to enhance the understanding of cardiotoxicity in platinum-based chemotherapy, informing clinical practices and promoting patient-centric care.

Metastasis remains a critical challenge in cancer treatment and the leading cause of cancer-related mortality. Ongoing research has demonstrated the key role of extracellular vesicles (EVs) in facilitating communication between distant organs. Cancer cells release a substantial number of EVs that carry distinct cargo molecules, including oncogenic proteins, DNA fragments, and various RNA species. Upon uptake, these cargo molecules profoundly influence the biology of both normal and cancerous cells. This review consolidates the understanding of how EVs promote tumorigenesis by regulating processes such as proliferation, migration, metastasis, angiogenesis, stemness, and immunity. The exploration of EVs as a non-invasive method for cancer detection holds great promise, given that different cancer types exhibit unique protein and RNA signatures that can serve as valuable biomarkers for early diagnosis. Furthermore, growing interest exists in the potential bioengineering EVs for use as prospective therapeutic tools for cancer treatment.

Epithelial-mesenchymal transition (EMT) promotes several cancers by increasing tumor cell motility, disrupting epithelial cell phenotypes, apical-basal polarity, and intracellular connections, and enhancing tumor resistance to immunotherapy and chemotherapy. Mesenchymal-epithelial transition (MET), the opposite of EMT, causes tumor metastasis. EMT drives primary tumor cells, whereas MET inhibits them. Importantly, the complex network of EMT includes cell-cell interactions in the tumor microenvironment. Transcription factors, post-translational regulation, cytokine-mediated signaling, and microRNAs control EMT. In this review, we discussed how molecular mechanisms, signaling networks, and epithelial/mesenchymal states affect cancer treatment resistance and the tumor microenvironment. Research on immunotherapy and chemotherapy problems associated with EMT suggests that targeting EMT might be a potential cancer treatment resistance strategy.

Skin cancer is one of the most prevalent cancers in the world, and its incidence and mortality rates are increasing continuously, mostly in regions with white-skinned inhabitants. The types of skin cancer vary in their origin and clinical appearances and also differ in their extensiveness. The continents of the world have different scenarios of skin cancer prevalence. This review aims to explore the different types of skin cancer, their clinical features, and their worldwide prevalence based on the literature. Literature from different electronic databases, including Google Scholar, ResearchGate, PubMed, Scopus, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Elsevier, and Springer, were collected through a literature search using specific keywords such as "skin cancer", "skin cancer types", "melanoma", "non-melanoma", "skin cancer continental prevalence" or similar keywords. The search included English publications from 2000 to 2024. Melanoma skin cancer (MSC) ranks 17th in global prevalence, with the highest incidence and deaths occurring in Europe, However, Australia and New Zealand record the highest incidence and mortality rates. Asia has a lower incidence rate of melanoma, but a higher mortality rate. Superficial spreading melanoma (SSM) is the most common type of MSC. Non-melanoma skin cancers (NMSCs) have the highest incidence in North America, with the highest number of deaths occurring in Asia, Australia and New Zealand have the highest incidence rates for basal cell carcinoma (BCC). BCC is the most commonly diagnosed skin cancer worldwide and the most prevalent form of NMSCs; however, squamous cell carcinoma is the most aggressive form of NMSCs, causing more deaths. NMSCs are the most prevalent cancers worldwide, causing most skin cancer-related deaths. The prevalence of skin cancer rising globally, with several continents experiencing higher incidence and mortality rates. The types and subtypes of skin cancer are becoming more common among clinically diagnosed cancers. This review comprehensively describes skin cancer types and their prevalence worldwide. However, the actual prevalence of skin cancer in these countries should be investigated. Further research on the prevalence of skin cancer across different continents is required to develop more effective cancer management strategies and control the spread of the disease.

Whole-tissue autologous therapeutic vaccines (WATVs) are a form of cancer immunotherapy that use a patient's own pathological tissue. Concerns exist regarding the potential of WATVs to induce autoimmunity or the spread of cancer; however, their adverse events (AEs) have not been adequately studied. This literature review primarily aimed to evaluate the risks of autoimmunity and cancer seeding associated with using WATVs in human clinical trials. Its secondary objectives included assessing the incidence of AEs graded 1-5 using the Common Terminology Criteria for Adverse Events v5.0.

The inclusion criteria were any clinical trial using human subjects in which at least part of the cancer vaccine was derived from the patient's own tumor tissue, which likely preserved the unique tumor-associated antigens (TAAs) present in the patient's tumor (i.e., whole-tissue). Tumor vaccine trials that used limited TAAs or highly processed tumor antigens were excluded. Published clinical trials were searched using Google Scholar until March 2024. The authors elaborated on the risk of bias in such cases, as indicated. All reviewed publications were searched for evidence of autoimmunity, cancer seeding, and other AEs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement guided the review.

Data from 55 human clinical trials, abstracts, case reports, and unpublished data were analyzed, including 3323 patients treated with WATVs for various cancers. The primary outcomes were: (1) no documented cases of WATV-induced autoimmunity, (2) no documented cases of WATV-induced spreading or seeding of noninfectious cancers, and (3) the observed 0.24% (2/838) risk of spreading or seeding infectious cancers was attributed to inadequate sterilization. The secondary outcomes were: (1) no deaths were attributed to WATV therapy, (2) 0.18% (6/3323) incidence of grade 4 AEs, (3) 0.42% (14/3323) incidence of grade 3 AEs, (4) the incidence of grades 1-2 AEs was 52.21% (478/916).

WATVs carry no risk of inducing autoimmunity and essentially no risk of cancer seeding if properly sterilized. WATVs also exhibit a side effect profile comparable to that of routine vaccinations, with common, mild, and transient adverse effects. The combined risk of grade 3 and 4 AEs was 0.60% (20/3323). No deaths were causally associated with WATV treatment.

To date, no direct comparisons have been performed to compare the effectiveness of all epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) against EGFR mutation-positive non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of EGFR-TKIs in patients with EGFR mutation-positive NSCLC.

We conducted a network meta-analysis of randomized controlled trials comparing osimertinib, lazertinib, aumolertinib, befotertinib, furmonertinib, dacomitinib, afatinib, erlotinib, gefitinib, icotinib, and chemotherapy. Pooled estimations of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity (grade ≥ 3 adverse events) were performed within the Bayesian framework.

Twenty-three trials involving 11 treatments were included. All EGFR-TKIs improved PFS relative to chemotherapy, except for icotinib (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.26-1.44). All EGFR-TKIs demonstrated significant ORR benefits over chemotherapy. Osimertinib seemed to prolong PFS compared with icotinib (HR = 0.29, 95% CI: 0.1-0.86), gefitinib (HR = 0.39, 95% CI: 0.21-0.74), and erlotinib (HR = 0.53, 95% CI: 0.29-1.0). In addition, osimertinib showed favorable superiority in improving OS compared with chemotherapy (HR = 0.6, 95% CI: 0.43-0.82), gefitinib (HR = 0.61, 95% CI: 0.45-0.83), erlotinib (HR = 0.65, 95% CI: 0.48-0.89), and afatinib (HR = 0.65, 95% CI: 0.44-0.94). Among these regimens, afatinib showed the highest ORR (cumulative probability: 96.96%). Icotinib was associated with minimal toxicity among the EGFR-TKIs, followed by furmonertinib and osimertinib. Moreover, the toxicity spectra differed among the EGFR-TKIs. Subgroup analyses of patients with two common types of EGFR mutations indicated that furmonertinib possessed the greatest PFS benefit in patients with exon 19 deletion, and lazertinib showed the greatest PFS benefit in patients with Leu858Arg mutation. We also identified differences between EGFR-TKIs in prolonging PFS in patients with brain metastasis.

Osimertinib is the first choice of treatment with considerable efficacy and safety for EGFR mutation-positive NSCLC. The treatments associated with the best PFS in patients with exon 19 deletions and Leu858Arg mutations were furmonertinib and lazertinib, respectively.

Population-based penetrance studies of breast cancer gene 1/2 (BRCA1/2) pathogenic or likely pathogenic (P/LP) variants in the Eastern Chinese population are currently lacking; thus, we aimed to investigate the penetrance of breast cancer and other malignant tumors among BRCA1/2 P/LP variant carriers using a population-based breast cancer cohort from communities in Eastern China.

Between July 2019 and March 2021, we tested 2216 breast cancer probands from Chinese communities for BRCA1/2 mutations and collected detailed information on the age, survival status, and malignancy history of first-degree relatives. The kin-cohort method was used to calculate the penetrance of breast cancer and other malignant tumors.

Of the 2216 breast cancer probands, 109 (4.90%) carried BRCA1/2 P/LP variants, 49 in the BRCA1 gene and 60 in the BRCA2 gene. The penetrance of female breast cancer by 85 years of age was 22.50% and 18.20% in BRCA1 and BRCA2 P/LP variant carriers, respectively. The penetrance of ovarian cancer by 85 years of age was 26.00% in BRCA1 P/LP variant carriers. The penetrance of other malignancies did not reach statistical significance owing to the small number of events.

Our findings showed that breast cancer penetrance among BRCA1 and BRCA2 P/LP variant carriers was 22.50% and 18.20%, respectively, which suggests that prophylactic mastectomy may not be necessary for such Chinese individuals.

ClinicalTrials.gov; https://clinicaltrials.gov/ct2/show/NCT04265937.

Breast cancer (BC) is the most diagnosed cancer worldwide, and patients' survival decreases with metastasis. We conducted a retrospective study using data derived from the Surveillance, Epidemiology, and End Results (SEER) database and clinicopathological data to construct a clinical predictive model to predict the risk and prognosis of lung metastasis (LM) in patients with different subtypes of BC and validate its performance.

A total of 1650 patients from the SEER database between 2011 and 2015 were enrolled in this study. Cox regression analysis was performed to identify prognostic factors for breast cancer lung metastasis (BCLM). A nomogram was constructed using the independent prognostic factors. The concordance index (C-index), area under the curve (AUC) value, calibration curve, and decision curve analysis (DCA) were used to test the prediction accuracy of the nomogram. External validation (n = 112) was performed using clinical data from the Affiliated Hospital of Qinghai University and the General Hospital of Ningxia Medical University.

Multivariate Cox regression analyses suggested that age, grade, surgery, chemotherapy, subtype, and liver, bone, and brain metastases were independent prognostic factors for overall survival (OS). Kaplan-Meier survival analysis showed that the median survival times of patients with human epidermal growth factor receptor 2 (HER2)-positive, luminal A, luminal B, and triple-negative BC were 25 (95% confidence interval [CI], 20-37), 27 (95% CI, 23-29), 35 (95% CI, 30-44), and 12 (95% CI, 11-14), respectively. The C-indexes of the nomogram for predicting OS of the SEER training, SEER validation, and clinical validation cohorts were 0.7, 0.6, and 0.6, respectively, and the calculated AUCs at 3 years were 0.765, 0.794, and 0.799, respectively. The calibration curve indicates that the nomogram possessed a high level of accuracy.

Our nomogram demonstrates significant predictive value, indicating that molecular subtypes, brain metastasis, and liver metastasis are closely associated with the prognosis of patients with LM. This information can guide clinical practice.

Despite the country's substantial liver cancer burden, there is limited research on the factors influencing the place of death (POD) of patients with liver cancer in China. This study aimed to delineate POD distribution among patients with liver cancer, identify the factors associated with hospital deaths, and offer valuable insights for the government to develop healthcare policies.

Data from 2013 to 2020 were obtained from the National Mortality Surveillance System (NMSS) of China. This analysis focused on the distribution of POD among individuals who succumbed to liver cancer. Variations in characteristic distributions across different categories were evaluated using a chi-squared test. We also applied a multilevel logistic regression analysis to identify the factors associated with hospital liver cancer deaths. The proportional change in variance was computed to evaluate the contributions of different factors in the model.

From 2013 to 2020, the NMSS reported a total of 608,789 liver cancer-related deaths, of which 440,079 (72.29%) died at home, and 158,291 (26.00%) died in the hospital. Home remained the preferred POD among patients with liver cancer. The results demonstrated that female patients, aged between 0 and 14 years, of Han ethnicity, living in urban areas, unmarried, highly educated, and either employed in a professional, staff, or civil servant capacity, or retired patients tended to end their lives in the hospital.

In China, home continues to be the predominant POD for patients with liver cancer, with demographic and socioeconomic factors significantly influencing whether a hospital is their POD. Enhancing healthcare policymakers' understanding of the factors influencing the place of death for patients with liver cancer may assist in creating a more equitable distribution of healthcare resources and providing a variety of choices for minorities with distinct preferences for end-of-life care.

慢性粒单核细胞白血病（CMML）是一种罕见的恶性血液疾病，被归类为骨髓增生异常/骨髓增生性肿瘤（MDS/MPN）。¹它具有进展为急性髓性白血病的显著风险，并且通常与不良预后相关。²CMML主要影响老年人，治疗通常涉及根据患者年龄和整体健康状况定制的去甲基化治疗。³然而，接受去甲基化治疗的CMML患者的完全缓解率为<20%，并经常伴有严重的副作用。¹在这里，我们讨论了一个84岁的男性病例，他在6年前被诊断为CMML，在去甲基化治疗后经历了显著的骨髓抑制。通过将多组学数据与生物信息学相结合，我们开发并应用了一种新的曲美替尼单药治疗方法。这种治疗导致造血功能和总体生活质量的显著改善，为管理CMML提供了一种有前途的策略。

胃肠道间质瘤(GIST)是胃肠道最常见的间叶性肿瘤，由原癌基因突变驱动c-试剂盒或血小板衍生生长因子α（PDGFRA）基因在85%-90%的病例中。³其他突变很少见，临床效果未知。伊马替尼是一种酪氨酸激酶抑制剂（TKI），被用作一线治疗，在70%-85%的晚期胃肠道间质瘤患者中赋予长达5年的中位生存期。³这种反应与肿瘤的突变状态相关。外显子11突变与良好应答相关，而外显子9、13和17的突变可能导致对伊马替尼的不同应答。关于外显子17编码的激活环结构域突变患者对伊马替尼反应的数据不足。在0.5%的所有GIST中观察到该突变。¹¹在此，我们讨论了一个罕见原癌基因的GIST患者的病例c-成套工具外显子17错义突变(c.2466T>A；Asn822Lys).患者接受伊马替尼治疗3个月，产生部分缓解（PR）。