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Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression

《医学前沿（英文）》 2024年第18卷第3期页码 430-445 doi: 10.1007/s11684-023-1049-z

摘要： Crosstalk between cancer cells and the immune microenvironment is determinant for liver cancer progression. A tumor subpopulation called liver cancer stem cells (CSCs) significantly accounts for the initiation, metastasis, therapeutic resistance, and recurrence of liver cancer. Emerging evidence demonstrates that the interaction between liver CSCs and immune cells plays a crucial role in shaping an immunosuppressive microenvironment and determining immunotherapy responses. This review sheds light on the bidirectional crosstalk between liver CSCs and immune cells for liver cancer progression, as well as the underlying molecular mechanisms after presenting an overview of liver CSCs characteristic and their microenvironment. Finally, we discuss the potential application of liver CSCs-targeted immunotherapy for liver cancer treatment.

关键词： liver cancer cancer stem cell immune cell immunotherapy

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Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

《医学前沿（英文）》 2021年第15卷第6期页码 942-942 doi: 10.1007/s11684-021-0876-z

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Progress and challenges in RET-targeted cancer therapy

《医学前沿（英文）》 2023年第17卷第2期页码 207-219 doi: 10.1007/s11684-023-0985-y

摘要： The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

关键词： pralsetinib selpercatinib RET-alteration lung cancer thyroid cancer tumor-agnostic therapy drug resistance

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Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

《医学前沿（英文）》 2018年第12卷第4期页码 361-373 doi: 10.1007/s11684-018-0656-6

摘要：

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.

关键词： epithelial-to-mesenchymal transition cancer metastasis cancer stem cell

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Metformin for cancer prevention

Yonghua Yang

《医学前沿（英文）》 2011年第5卷第2期页码 115-117 doi: 10.1007/s11684-011-0112-3

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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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Low-dose CT for lung cancer screening: opportunities and challenges

null

《医学前沿（英文）》 2018年第12卷第1期页码 116-121 doi: 10.1007/s11684-017-0600-1

摘要：

Lung cancer is among the most frequently diagnosed cancers worldwide and the leading cause of cancer death in both males and females. Screening for lung cancer coupled with earlier intervention has long been studied as an approach to mortality reduction. However, minimal progress was achieved until recently, when low-dose spiral computed tomography (LDCT) screening demonstrated a 20% reduction in mortality from lung cancer in a randomized controlled trial (RCT), the National Lung Screening Trial, from the United States. On the basis of this finding, LDCT has been recommended for lung cancer screening in high-risk populations by several clinical guidelines. However, results from the following independent RCTs in Europe failed to show consistent conclusions. In addition, intractable problems gradually emerged with the progress of LDCT screening. This paper summarizes and discusses the main observations and challenges of LDCT screening for lung cancer. Before spreading implementation of LDCT screening, challenges, including high false-positive rates, overdiagnosis, enormous costs, and radiation risk, must be addressed. Complementary biomarkers and technical improvement are expected in the field of lung cancer screening in the near future.

关键词： lung cancer low-dose computerized tomography early detection opportunities challenges

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Exploring the cancer genome in the era of next-generation sequencing

null

《医学前沿（英文）》 2012年第6卷第1期页码 48-55 doi: 10.1007/s11684-012-0182-x

摘要：

The emergence of next-generation sequencing technologies has led to dramatic advances in cancer genome studies. The increased efficiency and resolution of next-generation sequencing greatly facilitate the detection of genetic, genomic, and epigenomic alterations, such as single nucleotide mutations, small insertions and deletions, chromosomal rearrangements, copy number variations, and DNA methylation. Comprehensive analysis of cancer genomes through approaches of whole genome, exome, and transcriptome sequencing has significantly improved the understanding of cancer biology, diagnosis, and therapy. The present study briefly reviews the recent pioneering studies on cancer genome sequencing and provides an unprecedented insight into the landscape of genomic alterations in human sporadic cancers.

关键词： next-generation sequencing cancer genome whole genome sequencing exome transcriptome

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Developments in cancer prevention and treatment using traditional Chinese medicine

Hongsheng Lin, Jie Liu, Ying Zhang

《医学前沿（英文）》 2011年第5卷第2期页码 127-133 doi: 10.1007/s11684-011-0137-7

摘要： Through the joint efforts of several generations of practitioners in traditional Chinese medicine (TCM) and integrated medicine of oncology, we have made some achievements in cancer treatment using TCM in over 50 years, including treatment concepts, methods, and basic and clinical research. Currently, TCM plays an indispensable role in cancer prevention and treatment. However, we also clearly recognize that there are some issues that have yet to be resolved. In the future, cancer treated with TCM will face unprecedented opportunities and challenges. This article reviews the developments of TCM in the treatment of cancer.

关键词： traditional Chinese medicine (TCM) cancer

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Disparities in 36 cancers across 185 countries: secondary analysis of global cancer statistics

《医学前沿（英文）》 doi: 10.1007/s11684-024-1058-6

摘要： Disparities in 36 cancers across 185 countries: secondary analysis of global cancer statistics

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Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

null

《医学前沿（英文）》 2012年第6卷第4期页码 376-380 doi: 10.1007/s11684-012-0228-0

摘要：

The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance. Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a, a vital downstream effector of the PI3K-AKT-FOXO signaling pathway. Intriguingly, FOXM1 and FOXO3a also compete for binding to the same gene targets, which have a role in chemotherapeutic drug action and sensitivity. An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients, and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.

关键词： FOXO3a FOXM1 transcription factor cancer drug resistance tumorigenesis

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Intracellular and extracellular TGF-β signaling in cancer: some recent topics

null

《医学前沿（英文）》 2018年第12卷第4期页码 387-411 doi: 10.1007/s11684-018-0646-8

摘要：

Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.

关键词： TGF-β EMT lung cancer pancreatic cancer latent form immune function GARP

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Identification of cancer gene fusions based on advanced analysis of the human genome or transcriptome

null

《医学前沿（英文）》 2013年第7卷第3期页码 280-289 doi: 10.1007/s11684-013-0265-3

摘要：

Many gene fusions have been recognized as important diagnostic and/or prognostic markers in human malignancies. In recent years, novel gene fusions have been identified in cases without prior knowledge of the genetic background. Accompanied by a powerful computational data analysis method, new genome-wide screening approaches were used to detect cryptic genomic aberrations. This review focused on advanced genome-wide screening approaches in fusion gene identification, such as microarray-based approaches, next-generation sequencing, and NanoString nCounter gene expression system. The fundamental rationale and strategy for fusion gene identification using each biotech platform are also discussed.

关键词： gene fusion cancer microarray next-generation sequencing NanoString nCounter system

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Artificial intelligence methods available for cancer research

《医学前沿（英文）》 doi: 10.1007/s11684-024-1085-3

摘要： Artificial intelligence methods available for cancer research

关键词： research

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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