Cancer Innovation

Glioblastoma (GBM) is the most common primary central nervous system tumor, whose prognosis remains poor under the sequential standard of care, such as neurosurgery followed by concurrent temozolomide radiochemotherapy and adjuvant temozolomide chemotherapy in the presence or absence of tumor treating fields. Accordingly, the advent of molecular targeted therapy and immunotherapy has opened a new era of tumor management. A diverse range of targeted drugs have been tested in patients with GBM in phase III clinical trials. However, these drugs are ineffective for all patients, as evidenced by the fact that only a minority of patients in these trials showed prolonged survival. Furthermore, there are several published phase III clinical trials that involve immune checkpoint inhibitors, peptide vaccines, dendritic cell vaccines, and virotherapy. Accordingly, this review comprehensively overviews existing studies of targeted drugs and immunotherapy for glioma and discusses the challenge and perspective of targeted drugs and immunotherapy for glioma to clarify future directions.

Yuekun Wang

Shenglan Li

Yichen Peng

Wenbin Ma

Yu Wang

Wenbin Li

Progress in phase III clinical trials of molecular targeted therapy and immunotherapy for glioblastoma

胶质母细胞瘤分子靶向治疗和免疫治疗III期临床试验进展

Although there have been significant advancements in the treatment modalities for gastric cancer (GC) in recent years, the overall prognosis remains poor, particularly for individuals in advanced stages. The absence of a sensitive tumor marker in GC is a crucial factor contributing to this challenge.

Dengfeng Ren

Fuxing Zhao

Jinming Li

Xinjian Guo

Xinfu Ma

Yonghui Zheng

Guoshuang Shen

Jiuda Zhao

lncRNA TCONS_00251376 promotes the proliferation and migration of gastric cancer cell through upregulating ETV1

lncRNA TCONS_00251376 通过上调ETV1促进胃癌细胞增殖和迁移

Abstract Background The incidence of alcohol‐associated cancers is higher within Asian populations having an increased prevalence of an inactivating mutation in aldehyde dehydrogenase 2 ( ALDH2 ), a mitochondrial enzyme required for the clearance of acetaldehyde, a cytotoxic metabolite of ethanol. The role of alcohol consumption in promoting lung cancer is controversial, and little attention has been paid to the association between alcohol drinking and pulmonary ALDH2 expression. Methods We performed a comprehensive bioinformatic analysis of multi‐omics data available in public databases to elucidate the role of ALDH2 in lung adenocarcinoma (LUAD). Results Transcriptional and proteomic data indicate a substantial pulmonary expression of ALDH2, which is functional for the metabolism of alcohol diffused from the bronchial circulation. ALDH2 expression is higher in healthy lung tissue than in LUAD and inhibits cell cycle, apoptosis, and epithelial–mesenchymal transition pathways. Moreover, low ALDH2 mRNA levels predict poor prognosis and low overall survival in LUAD patients. Interestingly, ALDH2 expression correlates with immune infiltration in LUAD. Conclusions A better understanding of the role of ALDH2 in lung tumor progression and immune infiltration might support its potential use as a prognostic marker and therapeutic target for improving immunotherapeutic response.

Silvia Baldari

Annalisa Antonini

Giuliana Di Rocco

Gabriele Toietta

Expression pattern and prognostic significance of aldehyde dehydrogenase 2 in lung adenocarcinoma as a potential predictor of immunotherapy efficacy

肺腺癌中醛脱氢酶2的表达模式及预后意义：作为免疫治疗疗效潜在预测因子的研究

Abstract Background Polyamines play important roles in cell growth and proliferation. Polyamine metabolism genes are dysregulated in various tumors. Some polyamine metabolism genes are regulated by transcription factors. However, the transcription factors that regulate polyamine metabolism genes have not been completely identified. Additionally, whether any of the transcriptional regulations depend on tumor heterogeneity and the tumor microenvironment has not been investigated. Methods We used bulk RNA‐seq data to identify dysregulated polyamine metabolism genes and their transcription factors across breast cancer subtypes. Genes highly correlated with polyamine changes were obtained, and their subtype‐specific expressions were checked in tumor microenvironment cells using single‐cell RNA (scRNA)‐seq data. Gene Ontology enrichment analysis was used to explore their molecular functions and biological processes, and survival analysis was used to examine the impact of these genes on therapeutic outcome. Results We first analyzed the dysregulation of polyamine synthesis, catabolism, and transport in four breast cancer subtypes. Genes such as AGMAT and CAV1 were dysregulated across all subtypes, while APRT , SAT1 , and other genes were dysregulated in the more lethal subtypes. Among the dysregulated genes of polyamine metabolism, we focused on three genes ( SRM , APRT , and SAT1 ) and identified their transcription factors (SPI1 and IRF1 correspond to SAT1 , and IRF3 corresponds to SRM and APRT ). With scRNA‐seq data, we verified that these three transcription factors also regulated these three polyamine metabolism genes in the tumor microenvironment. Both bulk RNA‐seq and scRNA‐seq data indicated that these genes were specifically upregulated in high‐risk breast cancer subtypes, such as the basal‐like type. High expression of these genes corresponded to worse outcomes in the basal‐like subtype under chemotherapy and radiation treatment. Conclusion Our work identified three subtype‐specific transcription factors that regulate three polyamine metabolism genes in high‐risk breast cancer subtypes and the tumor microenvironment. Our results deepen the understanding of the role of polyamine metabolism in breast cancer and may help the clinical therapy of advanced breast cancer subtypes.

Qi Song

Yixuan Wang

Sen Liu

Subtype‐specific transcription factors affect polyamine metabolism and the tumor microenvironment in breast cancer

亚型特异性转录因子影响乳腺癌中的多胺代谢和肿瘤微环境

Abstract Primary cutaneous myoepithelial carcinoma is an extremely rare tumor, and to the best of our knowledge, it has never been reported to occur in the axilla. Furthermore, the pathological and clinical factors of cutaneous myoepithelial carcinoma are poorly understood and may considerably affect prognosis and treatment. Here, we report a case of a 44‐year‐old male patient who was diagnosed with primary cutaneous myoepithelial carcinoma in the axilla accompanied by extensive lymph node metastasis. After an enlarged resection of the left axillary mass, axillary lymph node dissection, and the administration of postoperative chemotherapy and local radiotherapy, there were no signs of tumor recurrence or metastasis. At the time of manuscript preparation, the patient was recurrence‐free. This case may contribute to the clinical management, diagnosis, and treatment of primary cutaneous myoepithelial carcinoma.

Xudong Zhu

Shenglong Li

A rare primary cutaneous myoepithelial carcinoma in the axilla accompanied by lymph node metastasis: A case report

腋窝原发性皮肤肌上皮癌伴淋巴结转移一例报告

Abstract Background Ultrasound‑guided vacuum‐assisted excision (UGVAE) and breast biopsy are widely used for the diagnosis and treatment of both benign and suspicious breast lesions. In this retrospective study, we aimed to determine the safety of UGVAE for benign breast lesions and provide guidance for clinical practice. Methods We analyzed clinical and pathological data of female patients who had undergone UGVAE between January 2015 and December 2017 at our institution. All breast lesions were categorized according to the Breast Imaging Reporting and Data System (BI‐RADS) before performing UGVAE. Results In our study cohort, UGVAE was used to resect 10,378 breast lesions from 5789 patients, and selected clinical and histopathological data were analyzed. The most common adverse events were postoperative bleeding (0.24%) and skin hypersensitivity (0.67%). The residual lesion rate was 2.27%. Fibroadenomas accounted for most of the benign lesions (7932 of 10,193; 77.82%). Breast cancer was diagnosed in 150 lesions from 128 patients. Multivariable binary logistic regression analyses showed that older age (odds ratio [OR] = 2.034, 95% confidence interval [CI]: 1.668–2.480, p &lt; 0.001), higher BI‐RADS category (OR = 9.514, 95% CI: 6.790–13.332, p &lt; 0.001), and larger legion size (OR = 1.048, 95% CI: 1.019–1.077, p = 0.001) were associated with an increased likelihood of breast cancer. Ninety‐six patients with breast cancer had undergone follow‐up treatment, achieving a 3‐year disease‐free survival rate of 97.2% and a 3‐year overall survival rate of 100%. Conclusions UGVAE is a safe and effective means of removing benign breast lesions, causing minimal postoperative trauma and fewer complications compared with open surgery. Moreover, UGVAE had little impact on the follow‐up treatment and survival of patients diagnosed with breast cancer.

Xuanni Tan

Juncheng Xuhong

Xiang Ai

Qin Niu

Jing Liu

Yi Zhang

Xiaowei Qi

Jun Jiang

Effectiveness of ultrasound‐guided vacuum‐assisted excision for treating benign breast lesions

超声引导下真空辅助切除治疗良性乳腺病变的有效性

Abstract Background Ibrutinib is a first‐line drug that targets Bruton's tyrosine kinase for the treatment of B cell cancer. However, cardiotoxicity induced by ibrutinib is a major side effect that limits its clinical use. This study aimed to investigate the mechanism of ibrutinib‐induced cardiotoxicity and evaluate the protective role of metformin. Methods The study utilized male C57BL/6 J mice, which were administered ibrutinib at a dosage of 30 mg/kg/day via oral gavage for 4 weeks to induce cardiotoxicity. Metformin was administered orally at 200 mg/kg/day for 5 weeks, starting 1 week before ibrutinib treatment. Cardiac function was assessed using echocardiography and electrophysiological studies, including surface electrocardiography and epicardial electrical mapping. Blood pressure was measured using a tail‐cuff system. Western blot analysis was conducted to evaluate the activity of the PI3K‐AKT and AMPK pathways, along with apoptosis markers. Results C57BL/6 J mice were treated with ibrutinib for 4 weeks to assess its effect on cardiac function. We observed that ibrutinib induced ventricular arrhythmia and abnormal conduction while reducing the left ventricular ejection fraction. Furthermore, pretreatment with metformin reversed ibrutinib‐induced cardiotoxicity. Mechanistically, ibrutinib decreased PI3K‐AKT activity, resulting in apoptosis of cardiomyocytes. Administration of metformin upregulated AMPK and PI3K‐AKT activity, which contributed to the improvement of cardiac function. Conclusion The study concludes that metformin effectively mitigates ibrutinib‐induced cardiotoxicity, including ventricular arrhythmia and cardiac dysfunction, by enhancing AMPK and PI3K‐AKT pathway activity. These findings suggest that metformin holds potential as a therapeutic strategy to protect against the adverse cardiac effects associated with ibrutinib treatment, offering a promising approach for improving the cardiovascular safety of patients undergoing therapy for B cell cancers.

Pengsha Li

Daiqi Liu

Pan Gao

Ming Yuan

Zhiqiang Zhao

Yue Zhang

Zandong Zhou

Qingling Zhang

Meng Yuan

Xing Liu

Gary Tse

Guangping Li

Qiankun Bao

Tong Liu

Mitigating ibrutinib‐induced ventricular arrhythmia and cardiac dysfunction with metformin

减轻伊布替尼诱导的室性心律失常和心脏功能障碍的二甲双胍治疗

Publication Information	Publisher: John Wiley and Sons Inc，Publishing cycle: ，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2022，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:
Journal Fees	$2800Details
Average review cycle	12 weeks

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Progress in phase III clinical trials of molecular targeted therapy and immunotherapy for glioblastoma

lncRNA TCONS_00251376 promotes the proliferation and migration of gastric cancer cell through upregulating ETV1

Expression pattern and prognostic significance of aldehyde dehydrogenase 2 in lung adenocarcinoma as a potential predictor of immunotherapy efficacy

Subtype‐specific transcription factors affect polyamine metabolism and the tumor microenvironment in breast cancer

A rare primary cutaneous myoepithelial carcinoma in the axilla accompanied by lymph node metastasis: A case report

lncRNA TCONS_00251376 promotes the proliferation and migration of gastric cancer cell through upregulating ETV1

Expression pattern and prognostic significance of aldehyde dehydrogenase 2 in lung adenocarcinoma as a potential predictor of immunotherapy efficacy

Subtype‐specific transcription factors affect polyamine metabolism and the tumor microenvironment in breast cancer

Effectiveness of ultrasound‐guided vacuum‐assisted excision for treating benign breast lesions

Mitigating ibrutinib‐induced ventricular arrhythmia and cardiac dysfunction with metformin

ISSN	2770-9183, 2770-9191
h-index	4