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Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamousnon-small-cell lung cancer: a retrospective analysis

《医学前沿（英文）》 2022年 第16卷 第4期   页码 610-617 doi: 10.1007/s11684-021-0827-8

摘要： Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation. Thus, 59 patients were included in the present retrospective study, 22 patients in the bevacizumab plus pemetrexed and platinum (B+PP) group, and 37 patients in the pemetrexed and platinum (PP) group. For the entire cohort of patients, the median OS was 33.3 months, and the 1-year and 2-year overall survival rates were 88.5% and 67.8%, respectively. The median OS and 1-year and 2-year OS rates were 20.5 months, 70.3% and 0%, respectively, in the B+PP group and 33.4 months, 97.0% and 89.4%, respectively, in the PP group (P <0.001). The incidence of grade≥3 adverse events was higher in the B+PP group than in the PP group (27.3% vs. 10.8%, respectively; P=0.204). Univariate and multivariate analyses suggested that the receipt of≥5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS, whereas the addition of bevacizumab was an unfavorable prognostic factor. With increased toxicities, the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.

关键词： bevacizumab     elderly patient     advanced non-small-cell lung cancer     overall survival     toxicity    

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Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis

null

《医学前沿（英文）》 2013年 第7卷 第2期   页码 157-171 doi: 10.1007/s11684-013-0272-4

摘要：

Non-small-cell lung cancer (NSCLC) is the most common cause of premature death among the malignant diseases worldwide. The current staging criteria do not fully capture the complexity of this disease. Molecular biology techniques, particularly gene expression microarrays, proteomics, and next-generation sequencing, have recently been developed to facilitate effectively its molecular classification. The underlying etiology, pathogenesis, therapeutics, and prognosis of NSCLC based on an improved molecular classification scheme may promote individualized treatment and improve clinical outcomes. This review focuses on the molecular classification of NSCLC based on gene expression microarray technology reported during the past decade, as well as their applications for improving the diagnosis, staging and treatment of NSCLC, including the discovery of prognostic markers or potential therapeutic targets. We highlight some of the recent studies that may refine the identification of NSCLC subtypes using novel techniques such as epigenetics, proteomics, or deep sequencing.

关键词： non-small-cell lung cancer     molecular typing     individualized medicine     molecular-targeted therapy     gene expression profiling    

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Compound C620-0696, a new potent inhibitor targeting BPTF, the chromatin-remodeling factor in non-small-celllung cancer

Jiahui Xu, Qianqian Wang, Elaine Lai Han Leung, Ying Li, Xingxing Fan, Qibiao Wu, Xiaojun Yao, Liang Liu

《医学前沿（英文）》 2020年 第14卷 第1期   页码 60-67 doi: 10.1007/s11684-019-0694-8

摘要： Bromodomain PHD-finger transcription factor (BPTF) is the largest subunit of the nucleosome remodeling factor and plays an important role in chromatin remodeling for gene activation through its association with histone acetylation or methylation. BPTF is also involved in oncogene transcription in diverse progressions of cancers. Despite clinical trials for inhibitors of bromodomain and extra-terminal family proteins in human cancers, no potent and selective inhibitor targeting the BPTF bromodomain has been discovered. In this study, we identified a potential inhibitor, namely, C620-0696, by computational docking modeling to target bromodomain. Results of biolayer interferometry revealed that compound C620-0696 exhibited high binding affinity to the BPTF bromodomain. Moreover, C620-0696 was cytotoxic in BPTF with a high expression of non-small-cell lung cancer (NSCLC) cells. It suppressed the expression of the BPTF target gene c-MYC, which is known as an oncogenic transcriptional regulator in various cancers. C620-0696 also partially inhibited the migration and colony formation of NSCLC cells owing to apoptosis induction and cell cycle blockage. Thus, our study presents an effective strategy to target a bromodomain factor-mediated tumorigenesis in cancers with small molecules, supporting further exploration of the use of these inhibitors in oncology.

关键词： BPTF     small molecule     epigenetics     non-small-cell lung cancer    

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Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

Fen LAN, Shengdao XIONG, Weining XIONG, Guopeng XU, Xiaoxia LU

《医学前沿（英文）》 2009年 第3卷 第1期   页码 41-44 doi: 10.1007/s11684-009-0009-6

摘要： This study aims to research the expression of spleen tyrosine kinase (Syk) in non-small cell lung cancer (NSCLC) and the relationship between Syk and clinicopathologic factors and p53. Immunohistochemistry was applied to detect the expression of Syk and p53 protein in 39 cases of NSCLC (23 cases of lung squamous cell cancer, 16 cases of lung adenocarcinoma) and tumor-surrounding normal lung tissues. The positive rate of Syk was 46.15% (18/39) and 100% (39/39) in NSCLC and tumor-surrounding normal lung tissues, respectively. The expression level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal lung tissues ( = 0.000). The Syk expression was positively correlated withthe p53 expression in NSCLC specimens ( = 0.025). There was no significant association between Syk expression and lymph node metastasis, differentiation degree, tumor size and tumor node metastasis (TNM). The present study demonstrated that Syk was aberrantly expressed in the NSCLC and might have a significant impact on tumor growth and progression.

关键词： Syk kinase     carcinoma     non-small-cell lung     tumor suppressor protein p53    

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Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

《医学前沿（英文）》 2023年 第17卷 第1期   页码 18-42 doi: 10.1007/s11684-022-0976-4

摘要： With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations (“target-dependent resistance”) and in the parallel and downstream pathways (“target-independent resistance”). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

关键词： non-small cell lung cancer     driver mutations     treatment strategy     resistant mechanism     immune-checkpoint inhibitors    

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Lobectomy by video-assisted thoracoscopic surgery (VATS) for early stage of non-small cell lung cancer

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 53-60 doi: 10.1007/s11684-011-0121-2

摘要：

Video-assisted thoracoscopic surgery (VATS) provides a new approach for treating early-stage lung cancer. Lobectomy by VATS has many advantages over conventional thoracotomy, such as shorter recovery time, less postoperative pain, and faster resumption of a normal lifestyle. However, there is still much debate on the role of VATS in lobectomy for the treatment of lung cancer. Concerns regarding safety, the extent of mediastinal lymph node dissection, and long-term survival have made some surgeons apprehensive of its validity for lung cancer. In this paper, we review the development of thoracoscopy, the present status of VATS for early stage of non-small cell lung cancer (NSCLC), and comparison between VATS and open thoracotomy in the management of NSCLC.

关键词： non-small cell lung cancer     video-assisted thoracoscopic surgery     lobectomy    

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Molecular markers and pathogenically targeted therapy in non-small cell lung cancer

Bo PENG BA , Jinnong ZHANG MD , Jamile S. WOODS MD , Wei PENG MD, PhD

《医学前沿（英文）》 2009年 第3卷 第3期   页码 245-255 doi: 10.1007/s11684-009-0044-3

摘要： Lung cancer is one of the most common human cancers and the number one cancer killer in the United States. In general, lung cancer includes small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), but NSCLC accounts for approximately 90% of lung cancer. The early diagnosis and therapy of lung cancer still presents a big challenge because validated screening tools, which can improve current early detection to reduce mortality from lung cancer, do not exist. Over the last decade, molecular genetic abnormalities have been described in NSCLC, including chromosomal aberrations, overexpression of oncogenes, and deletion and/or mutations in tumor suppressor genes. These molecular markers in NSCLC demonstrated close associations with the development of lung cancer such as Ras, the epidermal growth factor receptor (EGFR, or c-erbB-1), HER2 (c-erbB-2), c-Met, and Bcl-2. Therefore, this information may be applied for early cancer detection, classification, novel targeted therapy, and prognosis in NSCLC. Recent clinical data have revealed that targeted therapy might be the second-line therapy as an alternative approach. Currently, the targeted therapies are mainly focused on two lung cancer pathways, the EGFR and the vascular endothelial growth factor (VEGF) pathways. Some clinical trials are very encouraging, but some of them are not. However, these trials have not identified a subgroup of NSCLC with biomarkers. Therefore, it is very important to select NSCLC patients with biomarkers to match targeted agents so that we can further identify effectiveness of targeted therapy in the future.

关键词： lung cancer     carcinoma     non-small cell lung cancer     molecular markers     targeted therapy    

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CD47 blockade improves the therapeutic effect of osimertinib in non-small cell lung cancer

《医学前沿（英文）》 2023年 第17卷 第1期   页码 105-118 doi: 10.1007/s11684-022-0934-1

摘要： The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of “eat me” signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.

关键词： osimertinib     anti-CD47 antibody     combination strategy     ADCP     EGFR    

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Combined gemcitabine and CHK1 inhibitor treatment induces apoptosis resistance in cancer stem cell-likecells enriched with tumor spheroids from a non-small cell lung cancer cell line

null

《医学前沿（英文）》 2013年 第7卷 第4期   页码 462-476 doi: 10.1007/s11684-013-0270-6

摘要：

Evaluating the effects of novel drugs on appropriate tumor models has become crucial for developing more effective therapies that target highly tumorigenic and drug-resistant cancer stem cell (CSC) populations. In this study, we demonstrate that a subset of cancer cells with CSC properties may be enriched into tumor spheroids under stem cell conditions from a non-small cell lung cancer cell line. Treating these CSC-like cells with gemcitabine alone and a combination of gemcitabine and the novel CHK1 inhibitor PF-00477736 revealed that PF-00477736 enhances the anti-proliferative effect of gemcitabine against both the parental and the CSC-like cell populations. However, the CSC-like cells exhibited resistance to gemcitabine-induced apoptosis. Collectively, the spheroid-forming CSC-like cells may serve as a model system for understanding the mechanism underlying the drug resistance of CSCs and for guiding the development of better therapies that can inhibit tumor growth and eradicate CSCs.

关键词： drug resistance     cancer stem cell     checkpoint kinase 1 (CHK1)     PF-00477736     lung cancer     tumorigenicity    

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Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup

《医学前沿（英文）》 2022年 第16卷 第5期   页码 766-772 doi: 10.1007/s11684-021-0916-8

摘要： Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ≥ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gamma-glutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.

关键词： anlotinib     chemotherapy     short-term relapsed     small-cell lung cancer    

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Improved local control without elective nodal radiotherapy in patients with unresectable NSCLC treated by 3D-CRT

YANG Kunyu, LIU Li, ZHANG Tao, WU Gang, CAO Fengjun, WANG Jianhua

《医学前沿（英文）》 2007年 第1卷 第4期   页码 381-385 doi: 10.1007/s11684-007-0074-7

摘要： To investigate the influence of prophylactic elective nodal irradiation on the therapeutic results of definitive radiotherapy for patients with stage IIIA or stage IIIB unresectable non-small-cell lung cancer, 55 patients with clinically inoperable advanced non-small-cell lung cancer were studied. After four cycles of induction chemotherapy, the patients were divided into two groups at random. In one group, the elective nodal irradiation was included in clinical tumor volume (CTV) of definitive radiotherapy (ENI group); and in the other group, elective nodal irradiation was not included in CTV (non-ENI group). For the patients in the ENI group, the mean prescription dose for gross tumor volumes was 58.4 Gy, while for the patients in the non-ENI group, it was 65.8 Gy (<0.05). The responsive rates were 45.8% and 74.0% (<0.05), and the rate of the elective nodal failure (ENF) was 4.2% and 11.1%, respectively. Kaplan-Meier analysis showed that the mean local-progression-free survival time was 11.0 and 15.0 months, and one-year local-failure rates were 51.9% and 24.5% (<0.05). The median overall survival time was 13.0 and 15.0 months, respectively ( = 0.084). The one-year survival rates were 55.7% and 72.5%, and two-year survival rates were 0% and 19.9%. There was no significant difference in the occurrences of radiation-associated complications between the two groups. Our results showed that omitting elective nodal irradiation did not result in a high incidence of elective nodal failure. On the contrary, it decreased local failure by increasing prescription doses to the primary diseases and lymphadenopaphy, and thereby it may further prolong the patients survival.

关键词： significant difference     irradiation     unresectable non-small-cell     induction chemotherapy     influence    

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Fine-tuning cell organelle dynamics during mitosis by small GTPases

《医学前沿（英文）》 2022年 第16卷 第3期   页码 339-357 doi: 10.1007/s11684-022-0926-1

摘要： During mitosis, the allocation of genetic material concurs with organelle transformation and distribution. The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression, cell fate determination, and organismal homeostasis. Small GTPases belonging to the Ras superfamily regulate various cell organelles during division. Being the key regulators of membrane dynamics, the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases, such as cancer and Alzheimer’s disease. Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation. This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.

关键词： small GTPase     cell organelle     mitosis    

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Discovery of small molecule degraders for modulating cell cycle

《医学前沿（英文）》   页码 823-854 doi: 10.1007/s11684-023-1027-5

摘要： The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.

关键词： PROTAC     molecular glue     degrader     cell cycle     CDK     cyclin    

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Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation

null

《医学前沿（英文）》 2018年 第12卷 第2期   页码 224-228 doi: 10.1007/s11684-017-0538-3

摘要：

Bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) is a major cause of morbidity and mortality with limited treatment options. Lung transplantation (LTX) has been rarely reported as a treatment option for selected HSCT recipients with this problem. In the present study, we reported six patients who underwent LTX due to BOS after HSCT (two females, four males) from January 2012 to December 2014 in our center. The median time from HSCT to diagnosis of BOS was 2.5 years (ranging from 1 to 5 years). At a median time of 4 years (ranging from 2 to 5 years) after diagnosis of BOS, four patients received bilateral sequential LTX, and two patients received single LTX. One of the recipients suffered from mild acute rejection after LTX, another suffered from primary lung graft dysfunction on post-operation day 2, and three experienced fungal infections. The median time for follow-up after LTX was 19.5 months (ranging from 12 to 39 months). At present, all patients are alive with good functional capacity and no relapse of BOS and hematologic malignancy conditions. Patients who received bilateral LTX have better pulmonary functions than patients who received single LTX.

关键词： bronchiolitis obliterans syndrome (BOS)     hematopoietic stem cell transplantation (HSCT)     lung transplantation (LTX)    

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Orlistat induces ferroptosis-like cell death of lung cancer cells

《医学前沿（英文）》 2021年 第15卷 第6期   页码 922-932 doi: 10.1007/s11684-020-0804-7

摘要： Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P<0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.

关键词： orlistat     ferroptosis     FAF2     lung cancer    

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标题 作者 时间 类型 操作

Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamousnon-small-cell lung cancer: a retrospective analysis

期刊论文

Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis

null

期刊论文

Compound C620-0696, a new potent inhibitor targeting BPTF, the chromatin-remodeling factor in non-small-celllung cancer

Jiahui Xu, Qianqian Wang, Elaine Lai Han Leung, Ying Li, Xingxing Fan, Qibiao Wu, Xiaojun Yao, Liang Liu

期刊论文

Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

Fen LAN, Shengdao XIONG, Weining XIONG, Guopeng XU, Xiaoxia LU

期刊论文

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

期刊论文

Lobectomy by video-assisted thoracoscopic surgery (VATS) for early stage of non-small cell lung cancer

null

期刊论文

Molecular markers and pathogenically targeted therapy in non-small cell lung cancer

Bo PENG BA , Jinnong ZHANG MD , Jamile S. WOODS MD , Wei PENG MD, PhD

期刊论文

CD47 blockade improves the therapeutic effect of osimertinib in non-small cell lung cancer

期刊论文

Combined gemcitabine and CHK1 inhibitor treatment induces apoptosis resistance in cancer stem cell-likecells enriched with tumor spheroids from a non-small cell lung cancer cell line

null

期刊论文

Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup

期刊论文

Improved local control without elective nodal radiotherapy in patients with unresectable NSCLC treated by 3D-CRT

YANG Kunyu, LIU Li, ZHANG Tao, WU Gang, CAO Fengjun, WANG Jianhua

期刊论文

Fine-tuning cell organelle dynamics during mitosis by small GTPases

期刊论文

Discovery of small molecule degraders for modulating cell cycle

期刊论文

Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation

null

期刊论文

Orlistat induces ferroptosis-like cell death of lung cancer cells

期刊论文