Volume 02 · Issue 04 · 2024

消化道肿瘤，从食道癌到结肠直肠癌（CRCs），由于其高全球发病率和死亡率，对肿瘤学构成了重大挑战。^1,2这些恶性肿瘤的异质性强调了其病因的复杂性，其病因受遗传、表观遗传和环境因素的综合影响。³揭示这些肿瘤的分子复杂性和临床意义越来越重要，因为它们提供了可以为开发更有效的诊断、治疗和预防方法提供信息的见解。该特刊以“胃肠道肿瘤的基础研究与临床实践”为题，旨在重点介绍消化道肿瘤领域分子机制和临床研究的最新进展。我们希望通过展示这些发现，我们可以促进该领域专家之间的合作和对话，最终为这些癌症的诊断和治疗带来创新的观点。

Glioma is the most prevalent primary malignant tumor in the central nervous system (CNS). It represents a diverse group of brain malignancies characterized by the presence of various cancer cell types as well as an array of noncancerous cells, which together form the intricate glioma tumor microenvironment (TME). Understanding the interactions between glioma cells/glioma stem cells (GSCs) and these noncancerous cells is crucial for exploring the pathogenesis and development of glioma. To invesigate these interactions requires in vitro co-culture models that closely mirror the actual TME in vivo. In this review, we summarize the two- and three-dimensional in vitro co-culture model systems for glioma-TME interactions currently available. Furthermore, we explore common glioma-TME cell interactions based on these models, including interactions of glioma cells/GSCs with endothelial cells/pericytes, microglia/macrophages, T cells, astrocytes, neurons, or other multi-cellular interactions. Together, this review provides an update on the glioma-TME interactions, offering insights into glioma pathogenesis.

Skin cancer, a prevalent malignancy worldwide, poses significant health concerns owing to its increasing incidence. Autophagy, a natural cellular process, is a pivotal event in skin cancer and has advantageous and detrimental effects. This duality has prompted extensive investigations into medical interventions targeting autophagy modulation for their substantial therapeutic potential. This systematic review aimed to investigate the relationship between skin cancer and autophagy and the contribution and mechanism of autophagy modulators in skin cancer. We outlined the effectiveness and safety of targeting autophagy as a promising therapeutic strategy for the treatment of skin cancer. This comprehensive review identified a diverse array of autophagy modulators with promising potential for the treatment of skin cancer. Each of these compounds demonstrates efficacy through distinct physiological mechanisms that have been elucidated in detail. Interestingly, findings from a literature search indicated that none of the natural, synthetic, or semisynthetic compounds exhibited notable adverse effects in either human or animal models. Consequently, this review offers novel mechanistic and therapeutic perspectives on the targeted modulation of autophagy in skin cancer.

Breast cancer (BC) contributes greatly to global cancer incidence and is the main cause of cancer-related deaths among women globally. It is a complex disease characterized by numerous subtypes with distinct clinical manifestations. Immune checkpoint inhibitors (ICIs) are not effective in all patients and have been associated with tumor resistance and immunosuppression. Because amino acid (AA)-catabolizing enzymes have been shown to regulate immunosuppressive effects, this review investigated the immunosuppressive roles of indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan (Trp)-catabolizing enzyme, which is overexpressed in various metastatic tumors. It promotes immunomodulatory effects by depleting Trp in the regional microenvironment. This leads to a reduction in the number of immunogenic immune cells, such as effector T and natural killer (NK) cells, and an increase in tolerogenic immune cells, such as regulatory T (Treg) cells. The BC tumor microenvironment (TME) establishes a supportive niche where cancer cells can interact with immune cells and neighboring endothelial cells and is thus a feasible target for cancer therapy. In many immunological contexts, IDO1 regulates immune control by causing regional metabolic changes in the TME and tissue environment, which may further affect the maturation of systemic immunological tolerance. In the development of effective treatment targets and approaches, it is essential to understand the immunomodulatory effects exerted by AA-catabolizing enzymes, such as IDO1, on the components of the TME.

Surgical excision is an important part of the multimodal therapy strategy for patients with glioblastoma, a very aggressive and invasive brain tumor. While major advances in surgical methods and technology have been accomplished, numerous hurdles remain in the field of glioblastoma surgery. The purpose of this literature review is to offer a thorough overview of the current challenges in glioblastoma surgery. We reviewed the difficulties associated with tumor identification and visualization, resection extent, neurological function preservation, tumor margin evaluation, and inclusion of sophisticated imaging and navigation technology. Understanding and resolving these challenges is critical in order to improve surgical results and, ultimately, patient survival.

Currently, the need for new therapeutic strategies involving programmed cell death protein-1 (PD-1) monoclonal antibodies in the second-line setting of small cell lung cancer (SCLC) is urgent. This study aimed to evaluate the efficacy and safety of anlotinib plus penpulimab as a second-line treatment for patients with SCLC who progressed after first-line platinum-based chemotherapy.

This study included the patients from Cohort 4 of a single-arm, open-label, multicenter, phase II clinical trial. A safety run-in phase was performed under anlotinib (10/12 mg quaque die [QD], days 1-14) plus penpulimab (200 mg intravenously [IV], day 1) in a 21-day cycle, followed by the formal trial in which the patients received anlotinib (12 mg QD, days 1-14) plus penpulimab (200 mg IV, day 1) in a 21-day cycle. The primary endpoint of the safety run-in phase was safety. The primary endpoint of the formal trial phase was the objective response rate (ORR).

From April 28, 2020, to November 24, 2020, 21 patients were enrolled from 11 hospitals, including 2 in the safety run-in phase and 19 in the formal trial phase. In the formal trial phase, the ORR was 42.1% (8/19; 95% confidence interval [CI]: 17.7-66.6%). The median progression-free survival was 4.8 months (95% CI: 2.9-11.3 months), and the median overall survival was 13.0 months (95% CI: 4.6-not applicable [NA] months). The incidence of ≥grade 3 treatment-related adverse events (TRAEs) was 52.4% (11/21), and the incidence of treatment-related serious adverse events (AEs) was 28.6% (6/21). Two AE-related deaths occurred. The most common AEs were hypertension (57.1%, 12/21), hypothyroidism (42.9%, 9/21), and hypertriglyceridemia (38.1%, 8/21).

In patients with SCLC who progressed after first-line platinum-based chemotherapy, the second-line anlotinib plus penpulimab treatment demonstrates promising anti-cancer activity and a manageable safety profile, which warrants further investigation.

No. NCT04203719, https://clinicaltrials.gov/.

No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC). Although anlotinib and the programmed death-1 (PD-1) inhibitor camrelizumab are used as treatments for ESCC, the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported. Therefore, this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC.

Fifty-eight patients with advanced ESCC undergoing second-line therapy, either with anlotinib plus camrelizumab or anlotinib plus S-1, were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021. The primary endpoint was progression-free survival (PFS), with secondary endpoints including the objective response rate (ORR), disease control rate (DCR), and assessment of toxicity.

In patients with advanced ESCC, the anlotinib plus camrelizumab group (N = 32) exhibited longer PFS (8.00 vs. 4.53 months, P < 0.001), higher ORR (28.1 vs. 19.2%, P = 0.431), and higher DCR (87.5 vs. 65.4%, P = 0.045) than those in the anlotinib plus S-1 group (N = 26). Treatment-related adverse events (TRAEs) were predominantly grade 1/2 in both groups, with a higher incidence of grade 1/2 skin toxicity in patients treated with anlotinib plus camrelizumab (P = 0.033). Two patients (6.3%) developed grade 1/2 immune-related pneumonia. The incidence of grade 3/4 TRAEs did not differ significantly between the two groups. Multivariable Cox regression analysis identified that the drug regimen (P < 0.001), Eastern Cooperative Oncology Group performance status (P = 0.008), and differentiation grade (P = 0.008) were independent prognostic factors for PFS.

Anlotinib plus camrelizumab exhibited promising antitumor efficacy and manageable toxicity when used as a second-line treatment for advanced ESCC.

Patients with hematological malignancies face an increased risk of developing second primary neoplasms due to various factors, including immune system compromise and chemotherapy-related effects. However, the incidence and associated risk factors in older patients remain poorly understood. This study aimed to assess the incidence, identify risk factors, and evaluate their impact on survival outcomes among older patients with hematological malignancies.

This retrospective single-center study analyzed data from 163 patients, focusing on the occurrence of second primary neoplasms. Cumulative incidence rates were calculated, and risk factor analysis was conducted using a competing risk model.

Among 124 eligible patients with a total follow-up duration of 572.57 person-years, the incidence rate of second primary neoplasms was 15.72/1000 person-years. The standardized incidence ratio (SIR) was 0.81 (95% confidence interval [CI] [0.39-1.48], P = 0.518). History of radiotherapy emerged as a significant risk factor (subdistribution hazard ratio [SHR] = 21.61 [2.81-166.14], P = 0.003), whereas regular natural killer (NK) cell infusion was associated with reduced risk (SHR = 3.25 e-8 [9.81 e-9-1.08 e-7], P <0.001).

These findings underscore the importance of informing older patients with hematological malignancies about the long-term risks of second primary neoplasms. Healthcare providers should carefully weigh risk factors when formulating treatment strategies. The results are valuable for investigating the fundamental principles underlying the occurrence and progression of second primary neoplasms.

Although many epidemiological studies and meta-analyses have reported an association between autoimmune disorders and prostate cancer, none has reported a clear correlation or the direction of the association. The purpose of our study was to explore the potential relationship between autoimmunity-related disorders and prostate cancer using Mendelian randomization (MR).

We retrieved literature from PubMed using the keywords "autoimmune disorder" AND "prostate cancer" to find more clues on the correlation between prostate cancer and autoimmunity-related disorder. Based on this literature search, we selected 16 autoimmunity-related disorders that had genome-wide association study (GWAS) data and may be associated with prostate cancer. The inverse variance weighting (IVW) method was applied as our primary analysis for two-sample MR and multivariate MR analysis to estimate the odds ratio (OR) and 95% confidence interval (CI). We further verified the robustness of our conclusions using a series of sensitivity analyses.

The autoimmunity-related diseases selected include rheumatoid arthritis, ankylosing spondylitis, coxarthrosis, gonarthrosis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary sclerosing cholangitis, asthma, type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, autoimmune hyperthyroidism, psoriatic arthropathies, and polymyalgia rheumatica. The results of inverse variance weighting (IVW suggested that six diseases were associated with the development of prostate cancer. The three diseases that may increase the risk of prostate cancer are rheumatoid arthritis (P = 0.001), coxarthrosis (P < 0.001), and gonarthrosis (P = 0.008). The three possible protective factors against prostate cancer are primary sclerosing cholangitis (P = 0.001), autoimmune hyperthyroidism (P = 0.011), and psoriatic arthropathies (P = 0.001). Horizontal pleiotropy was not observed in the MR-Egger test.

Our findings provide predictive genetic evidence for an association between autoimmune disorders and prostate cancer. Further research is needed to explore the underlying mechanisms of comorbidities at the molecular level.

Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy. Transforming growth factor-β (TGF-β) signaling pathway-related genes are associated with multiple tumors, but their role in prognosis prediction and tumor microenvironment (TME) regulation in colon cancer is poorly understood. Using bioinformatics, this study aimed to construct a risk prediction signature for colon cancer, which may provide a means for developing new effective treatment strategies.

Using consensus clustering, patients in The Cancer Genome Atlas (TCGA) with colon adenocarcinoma were classified into several subtypes based on the expression of TGF-β signaling pathway-related genes, and differences in survival, molecular, and immunological TME characteristics and drug sensitivity were examined in each subtype. Ten genes that make up a TGF-β-related predictive signature were found by least absolute shrinkage and selector operation (LASSO) regression using colon cancer data from the TCGA database and confirmed using a Gene Expression Omnibus (GEO) dataset. A nomogram incorporating risk scores and clinicopathologic factors was developed to stratify the prognosis of patients with colon cancer for accurate clinical diagnosis and therapy.

Two TGF-β subtypes were identified, with the TGF-β-high subtype being associated with a poorer prognosis and superior sensitivity to immunotherapy. Mutation analyses showed a high incidence of gene mutations in the TGF-β-high subtype. After completing signature construction, patients with colon cancer were categorized into high- and low-risk subgroups based on the median risk score of the TGF-β-related predictive signature. The risk score exhibited superior predictive performance relative to age, gender, and stage, as evidenced by its AUC of 0.686. Patients in the high-risk subgroup had higher levels of immunosuppressive cell infiltration and immune checkpoints in the TME, suggesting that these patients had better responses to immunotherapy.

Patients with colon cancer were divided into two subtypes with different survival and immune characteristics using consensus clustering analysis based on TGF-β signaling pathway-related genes. The constructed risk prediction signature may show promise as a biomarker for evaluating the prognosis of colon cancer, with potential utility for screening individuals for immunotherapy.

巨灶性多发性骨髓瘤(MFMM)是多发性骨髓瘤(MM)中的一种独特实体，其特征是存在多发性溶解性骨病变，骨髓中的克隆浆细胞占<10%.^1,2修订的2022年中国MM状态诊断和治疗指南：在患有<多部位骨髓抽吸物中有10%克隆性浆细胞，应注意MFMM，其特征为单个或多发骨破坏性病变，常伴有周围软组织或淋巴结受累。³关于长期使用过继免疫疗法治疗MFMM的研究有限；因此，我们在此报告一例被诊断为MFMM的老年患者，该患者经历了严重的化疗副作用，随后接受了过继免疫治疗。值得注意的是，患者受益于14年的治疗[图1A].

在口腔癌患者中研究适应性生活方式干预对于改善治疗后结果至关重要。迄今为止，研究已经检查了针对饮食变化、身体活动和吸烟的循证干预措施，这些干预措施大大改善了存活率指标，包括提高生活质量（QOL）、优化总体健康和降低癌症复发风险。最终，治疗后、量身定制的适应性干预对于口腔癌患者维持健康和福祉至关重要。本文旨在为口腔癌幸存者提供适应性生活方式干预的全面概述，以改善治疗后的结果。本研究的主要目的是强调饮食调整、体育活动、戒烟计划和心理社会支持在提高生活质量、优化总体健康和降低癌症复发风险方面的重要性。这些发现强调了将循证干预纳入生存护理计划的必要性，使个体幸存者受益，并影响更广泛的医疗保健战略。

编辑部感到遗憾的是，一些以编辑为作者的文章在没有声明公平和严格的同行评审过程的情况下发表。以下陈述应作为脚注发表在文章的第一页。

作者遗憾文中呈现的“NK-κ B通路”应更正为“NF-κ B通路”，通讯作者中的“血液科”应更正为“血液科”。