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08 September 2023, Volume 50 Issue 9 Previous Issue    Next Issue

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Effects of Anhydroicaritin on the proliferation， migration and apoptosis of hepatocellular carcinoma cells Xiang Yuling, Tan Jiajie, Xiong Yuanguo, Zhao Lirong, Li Chen, Zhang Hong 2023, 50 (9):  513-519.  doi: 10.3760/cma.j.cn371439-20230523-00099 Abstract ( 83 )   HTML ( 13 )   PDF (3530KB) ( 33 )   Save Objective To investigate the effects of Anhydroicaritin （AHI）， an isopentenylated flavo-noid compound， on proliferation， migration and apoptosis of human hepatocarcinoma cell line MHCC-97H. Methods Human hepatocarcinoma cell line MHCC-97H and human normal liver cell line L02 were cultured in vitro. MHCC-97H cells were treated with 0， 20， 40， 80， 120， 160， 200 μg/ml of AHI respectively and L02 cells were treated with 0， 25， 50， 100， 150， 200， 400， 500 μg/ml of AHI respectively. CCK-8 and clone formation assay were used to detect cell proliferation. Scratch test was used to explore cell migration ability. Hoechst33342 assay and flow cytometer were used to detect cell apoptosis. The expressions of apoptosis-related proteins were detected by Western blotting. Results The cell viabilities of MHCC-97H cells treated with 0， 20， 40， 80， 120， 160， 200 μg/ml of AHI for 24 h were （100.00±0.00）%， （97.41±2.10）%， （96.58±3.23）%， （87.72±4.85）%， （78.33±3.76）%， （56.97±2.61）% and （15.25±2.51）% respectively， and there was a statistically significant difference （F=429.20， P<0.001）. There were statistically significant differences between 0 μg/ml and 80， 120， 160， 200 μg/ml of AHI treatment （all P<0.001）. The cell viabilities of L02 cells treated with 0， 25， 50， 100， 150， 200， 400， 500 μg/ml of AHI for 24 h were （100.00±0.00）%， （96.82±3.79）%， （95.36±3.43）%， （90.79±5.75）%， （77.67±5.66）%， （63.98±5.22）%， （34.22±4.01）% and （33.84±4.41）% respectively， and there was a statistically significant difference （F=233.20， P<0.001）. There were statistically significant differences between 0 μg/ml and 100， 150， 200， 400， 500 μg/ml of AHI treatment （all P<0.05）. The 24 h half maximal inhibitory concentration （IC50） value of AHI treated L02 cells was （300.20±17.10） μg/ml， which was significantly higher than that of MHCC-97H cells [（158.60±5.50） μg/ml]， and there was a statistically significant difference （t=13.65， P<0.001）. The cell clone numbers of MHCC-97H cells treated with 0， 120， 160 and 200 μg/ml of AHI for 24 h were 1 993.00±46.29， 1 355.00±54.84， 998.33±21.03 and 218.33±35.95 respectively， and there was a statistically significant difference （F=954.80， P<0.001）. There were statistically significant differences between 0 μg/ml and 120， 160， 200 μg/ml of AHI treatment （all P<0.001）. The healing rates of MHCC-97H cells treated with 0， 120， 160 and 200 μg/ml of AHI for 24 h were （51.68±1.93）%， （16.04±0.73）%， （8.88±0.31）% and （-6.94±0.46）% respectively， and there was a statistically significant difference （F=1 616.00， P<0.001）. There were statistically significant differences between 0 μg/ml and 120， 160， 200 μg/ml of AHI treatment （all P<0.001）. Hoechst33342 experiment showed that MHCC-97H cells treated with 0 μg/ml AHI showed uniform dark blue with a complete nuclear state under inverted microscope. Compared with 0 μg/ml AHI treated cells， cells in the 120， 160， 200 μg/ml AHI treatment groups wrinkled and broken， and nuclei were also morphologically abnormal， with some nuclei stained bright blue， and the situation became more obvious with increasing dose. The apoptosis rates of MHCC-97H cells treated with 0， 120， 160 and 200 μg/ml AHI for 24 h were （10.51±0.56）%， （42.23±0.87）%， （61.92±0.52）% and （72.05±0.74）% respectively， and there was a statistically significant difference （F=4 677.00， P<0.001）. There were statistically significant differences between 0 μg/ml and 120， 160， 200 μg/ml of AHI treatment （all P<0.001）. There were statistically significant differences among the different expression levels of Bax， Cleaved Caspase-3/Caspase-3， Cleaved Caspase-9/Caspase-9， and Bcl-2 proteins in MHCC-97H cells of 0， 120， 160， and 200 μg/ml of AHI treatment （F=30.43， P<0.001； F=212.80， P<0.001； F=475.30， P<0.001； F=10.75， P=0.004）. The Bax protein expression of 160 and 200 μg/ml was significantly increased than that of 0 μg/ml AHI （both P<0.001）. The Cleaved Caspase-3/Caspase-3， Cleaved Caspase-9/Caspase-9 protein expressions of 120， 160 and 200 μg/ml were significantly increased than those of 0 μg/ml AHI （all P<0.001）. The Bcl-2 protein expression of 120， 160， 200 μg/ml was significantly decreased compared with that of 0 μg/ml AHI （all P<0.05）. Conclusion AHI can inhibit the proliferation and migration of hepatocellular carcinoma cell line MHCC-97H， and promote its apoptosis. Figures and Tables | References | Related Articles | Metrics

Value of NLR， CEA combined with coagulation indicators in the differential diagnosis of benign and malignant breast nodules with a diameter ≤ 1.0 cm Wang Jing, Xu Wenting 2023, 50 (9):  520-526.  doi: 10.3760/cma.j.cn371439-20230513-00100 Abstract ( 101 )   HTML ( 8 )   PDF (1553KB) ( 20 )   Save Objective To explore the value of neutrophil to lymphocyte ratio （NLR）， carcinoembryonic antigen （CEA） combined with coagulation indicators prothrombin time （PT）， activated partialthromboplastin time （APTT）， thrombin time （TT）， fibrinogen （FIB） in the differential diagnosis of benign and malignant breast nodules with a diameter of ≤1.0 cm. Methods Patients with breast nodule diameter ≤1.0 cm who underwent physical examination in the Cancer Hospital of Xinjiang Medical University from January 2017 to March 2023 were selected as the study objects. Patients admitted from January 2017 to June 2020 were defined as the training set， and patients admitted from July 2020 to March 2023 were defined as the validation set. In the training set， there were 83 patients with benign breast nodules and 106 patients with breast cancer； In the validation set， there were 109 patients with benign breast nodules and 136 patients with breast cancer. The influencing factors of benign and malignant breast nodules were analyzed by logistic regression. Binary logistic regression was used to construct the diagnosis and prediction model of benign and malignant breast nodules. Receiver operating characteristic （ROC） curve was used to evaluate the diagnostic performance of each index and diagnostic prediction model for benign and malignant breast nodules. Results There were statistically significant differences between patients with benign breast nodules and patients with breast cancer in the training and validation sets in neutrophils（t=6.76， P<0.001； t=9.14， P<0.001）， lymphocytes （t=7.67， P<0.001； t=17.00， P<0.001）， NLR（t=13.97， P<0.001； t=17.41， P<0.001）， CEA （t=33.44， P<0.001； t=8.15， P<0.001）， PT （t=15.81， P<0.001； t=60.15， P<0.001）， APTT （t=39.50， P<0.001； t=16.34， P<0.001）， TT （t=13.34， P<0.001； t=14.37， P<0.001）， FIB （t=16.66， P<0.001； t=20.30， P<0.001）. The results of univariate analysis showed that neutrophils （OR=3.52， 95%CI： 1.26-5.37， P=0.036）， lymphocytes （OR=2.64， 95%CI： 1.52-3.72， P=0.033）， NLR （OR=1.96， 95%CI： 1.15-3.42， P<0.001）， CEA （OR=2.16， 95%CI： 1.29-3.05， P<0.001）， PT （OR=1.75， 95%CI： 1.17-2.69， P<0.001）， APTT （OR=3.11， 95%CI： 1.55-5.38， P<0.001）， TT （OR=2.59， 95%CI： 1.38-4.11， P<0.001）， FIB （OR=2.89， 95%CI： 1.36-4.55， P<0.001） were all influencing factors that affected the benign and malignant breast nodules with a diameter ≤1.0 cm. The results of multivariate analysis showed that NLR （OR=2.06， 95%CI： 1.32-2.76， P<0.001）， CEA （OR=1.19， 95%CI： 1.09-1.37， P=0.008）， PT （OR=1.63， 95%CI： 1.05-2.11， P<0.001）， APTT （OR=1.52， 95%CI： 1.13-2.34， P<0.001）， TT （OR=1.64， 95%CI： 1.14-2.74， P<0.001）， FIB （OR=1.42， 95%CI： 1.11-1.89， P<0.001） were all independent influencing factors on the benign and malignant breast nodules with a diameter ≤1.0 cm. ROC curve analysis results showed that the area under curve （AUC） of NLR， CEA， PT， APTT， TT， FIB in the diagnosis of breast cancer was 0.83， 0.65， 0.69， 0.72， 0.73， 0.70 respectively， in the training set. The sensitivity of NLR in the diagnosis of breast cancer was 76%， and the specificity was 69%. A diagnostic prediction model was established based on statistically significant indicators in multivariate analysis， with logit （P）=1.76×NLR+21.42×CEA+5.14×PT+5.34×APTT+5.78×TT+6.52×FIB. ROC curve analysis showed that the AUC of the diagnostic prediction model used for patient differential diagnosis in the training and validation sets was 0.81 and 0.80 respectively. The AUC of diagnosis prediction model for breast cancer diagnosis of patients aged ≤60 years old and >60 years old was 0.79 and 0.77 respectively， with sensitivity of 82% and 80%， specificity of 75% and 83% respectively. The AUC of diagnosis prediction model for breast cancer with tumor diameter <0.3 cm， 0.3-0.6 cm and 0.7-1.0 cm was 0.63， 0.74 and 0.91 respectively， with sensitivity of 68%， 73%， 81%， and specificity of 72%， 77%， 84%. Conclusion NLR， CEA， PT， APTT， TT and FIB are all independent influencing factors that affect the benign and malignant breast nodules with a diameter ≤1.0 cm. The prediction model constructed by NLR and CEA combined with coagulation indexes PT， APTT， TT and FIB has high diagnostic efficiency for benign and malignant breast nodules with a diameter ≤1.0 cm. Figures and Tables | References | Related Articles | Metrics

Relationships between HER2 protein expression and imaging features in HER2 positive breast cancer patients Feng Chengtian, Huang Furong, Cao Shiyu, Wang Jianyu, Nanding Abiyasi, Jiang Yongdong, Zhu Juanying 2023, 50 (9):  527-531.  doi: 10.3760/cma.j.cn371439-20221214-00101 Abstract ( 81 )   HTML ( 12 )   PDF (703KB) ( 16 )   Save Objective To investigate the relationships between the expression level of human epidermal growth factor receptor 2 （HER2） in HER2-positive breast cancer and the characteristics of ultrasound imaging and mammography. Methods The imaging data of 486 patients with HER2-positive breast cancer treated in the Harbin Medical University Cancer Hospital from January 2014 to December 2021 were retrospectively collected. The relationships between the expression level of HER2 and the imaging features of breast ultrasound and mammography were analyzed. Results 49.38% （240/486） of HER2-positive breast cancer patients were HER2 2+， and 50.62% （246/486） of HER2-positive breast cancer patients were HER2 3+. The age of HER2 2+ patients [（52.88±1.16） years] was older than the age of HER2 3+ patients [（49.59±1.00） years]， and there was a statistically significant difference （t=18.07， P<0.001）. There was a statistically significant difference of menstrual status between HER2 2+ patients and HER2 3+ patients （χ2=4.42， P=0.036）. There were statistically significant differences in the ultrasonography showed burr sign （χ2=8.37， P=0.010）， posterior echo （χ2=9.68， P=0.017）， axillary lymph node enlargement （χ2=15.77， P<0.001） between HER2 2+ patients and HER2 3+ patients. There was a statistically significant difference in the mammography showed whether there were lumps between HER2 2+ patients and HER2 3+ patients （χ2=15.81， P<0.001）. Conclusion The expression level of HER2 in HER2-positive breast cancer patients is related to burr sign， posterior echo， and axillary lymph node enlargement shown by ultrasound， as well as lumps shown by mammography， which can provide certain information for clinical prediction of malignant degree of breast cancer， prognosis and individualized treatment plan. Figures and Tables | References | Related Articles | Metrics

Effects of intrathecal infusion chemotherapy on intracranial pressure in non-small cell lung cancer patients with leptomeningeal metastases by ultrasound measurement of optic nerve sheath diameter Xie Yu, Jiang Cheng, Huang Mingmin, Guo Aibin, Yin Zhenyu, Lin Yongjuan 2023, 50 (9):  532-539.  doi: 10.3760/cma.j.cn371439-20230428-00102 Abstract ( 70 )   HTML ( 6 )   PDF (1288KB) ( 14 )   Save Objective To evaluate the effects of intrathecal infusion chemotherapy on intracranial pressure （ICP） in non-small cell lung cancer （NSCLC） patients with leptomeningeal metastases （LM） by ultrasound measurement of the optic nerve beside the bed of optic nerve sheath diameter （ONSD）. Methods A total of 31 NSCLC-LM patients who underwent intrathecal infusion chemotherapy at Nanjing Drum Tower Hospital， Affiliated Hospital of Nanjing University Medical School from June 10， 2021 to December 25， 2022 were collected. The ONSD values were measured before and after the first lumbar puncture by bedside optic nerve ultrasound， and measured dynamically 30 min before intrathecal infusion chemotherapy （T0）， 30 min （T1）， 1 h （T2）， 2 h （T3）， 4 h （T4）， 6 h （T5）， and 24 h （T6） after intrathecal infusion chemotherapy. ICPONSD was calculated， with differences between ICPLP and ICPONSD， and differences between ONSD and ICPONSD series at different time being compared separately. Mean arterial pressure （MAP）， heart rate， and headache score were assessed and compared respectively at T0， T1， T2， T3， T4， T5 and T6. Spearman analysis was used to evaluate the correlation between the response assessment in neuro-oncology （RANO） score and ICP. Results Before the first lumbar puncture for cerebrospinal fluid drainage， ICPLP was （218.55±63.83） mmH2O， left eye， right eye， and binocular eyes ICPONSD were （217.28±57.17） mmH2O， （223.64±51.13） mmH2O， and （220.46±52.50） mmH2O respectively， in NSCLC-LM patients， with no statistically significant difference （F=0.77， P=0.463）. After first lumbar puncture for cerebrospinal fluid drainage， ICPLP was （214.68±58.01） mmH2O， left eye， right eye， and binocular eyes ICPONSD were （216.71±48.96） mmH2O， （216.62±47.18） mmH2O， and （216.67±47.86） mmH2O respectively， with no statistically significant difference （F=0.12， P=0.757）. At T0， T1， T2， T3， T4， T5， and T6， the MAP during intrathecal infusion chemotherapy was 89.80 （83.40， 93.67） mmHg， 95.00 （80.83， 99.37） mmHg， 91.86（79.88， 100.14） mmHg， 90.15（79.04， 100.55） mmHg， 105.14（88.55， 114.74） mmHg， 98.96 （81.72， 111.81） mmHg， and 89.29 （85.45， 100.38） mmHg， with a statistically significant difference （χ2=16.11， P=0.013）； heart rates were 80.00 （75.00， 84.50） times/min， 80.00 （72.50， 87.50） times/min， 74.00（66.00， 87.50） times/min， 82.00 （72.00， 90.00） times/min， 80.00 （70.50， 90.00） times/min， 77.00 （68.00， 91.00） times/min， 77.00 （71.50， 88.50） times/min， with no statistically significant difference （χ2=2.18， P=0.902）； headache scores were 2.00 （0.50， 3.00） score， 2.00 （1.00， 3.00） score， 2.00 （2.00， 3.00） score， 2.00 （1.00， 3.00） score， 2.00 （1.00， 2.00） score， 2.00 （1.00， 2.00） score， and 2.00 （0.00， 2.00） score， with no statistically significant difference （χ2=11.64， P=0.071）. At T0， T1， T2， T3， T4， T5， and T6， left eye， right eye， and binocular ONSD were （5.85±0.64） mm， （5.72±0.68） mm， （7.11±1.11） mm， （6.42±0.78） mm， （5.69±0.63） mm， （5.61±0.64） mm， （5.65±0.88） mm， （5.85±0.12） mm， （5.89±0.12） mm， （6.93±0.20） mm， （6.40±0.14） mm， （5.71±0.12） mm， （5.66±0.12） mm， （5.33±0.14） mm， （5.85±0.64） mm， （5.81±0.64） mm， （7.02±1.03） mm， （6.41±0.75） mm， （5.70±0.63） mm， （5.64±0.63） mm， （5.49±0.76） mm， with statistically significant differences （F=58.48， P<0.001； F=49.34， P<0.001； F=78.05， P<0.001）； ICPONSD were （222.81±56.81） mmH2O， （211.89±60.29） mmH2O， （335.12±98.32） mmH2O， （274.17±68.87） mmH2O， （208.77±56.12） mmH2O， （201.75±56.79） mmH2O， （205.59±78.36） mmH2O， （223.26±58.33） mmH2O， （227.08±61.68） mmH2O， （319.36±101.10） mmH2O， （272.33±69.61） mmH2O， （211.21±57.73） mmH2O， （206.51±57.22） mmH2O， （177.22±68.98） mmH2O， （223.03±57.24） mmH2O， （219.49±57.24） mmH2O， （327.24±91.56） mmH2O， （273.25±67.04） mmH2O， （209.99±56.26） mmH2O， （204.13±56.29） mmH2O， （191.40±67.95） mmH2O， with statistically significant differences （F=58.48， P<0.001； F=49.34， P<0.001； F=78.13， P<0.001）. The ONSD of the left eye， right eye， and binocular eyes and the corresponding ICPONSD increased significantly at T2 compared with T0， T1， T3， T4， T5， and T6， with statistically significant differences （all P<0.05）. Pre- and post-treatment RANO scores were 4.00 （3.00，7.00） score and 3.00 （2.00， 6.00） score respectively. Pre- and post-treatment RANO scores were positively correlated with ICPONSD in the left eye （r=0.55， P=0.001； r=0.60， P<0.001）， right eye （r=0.54， P=0.001； r=0.46， P=0.009） and binocular eyes ICPONSD （r=0.45， P=0.010； r=0.37， P=0.043）. Conclusion Intrathecal infusion chemotherapy for NSCLC-LM patients can cause a transient increase in ONSD and ICP， with the greatest effect at 1 hour after intrathecal infusion chemotherapy. RANO score is positively correlated with ICPONSD before and after treatment， which can provide an important reference for evaluating the efficacy of intrathecal infusion chemotherapy. Figures and Tables | References | Related Articles | Metrics

Reviews

Role of linc01410 in the occurrence and development of malignant tumors Liu Yang, Jiang Lulu, Guan Kaiwen, Zhou Yueyang, Kang Xiaohong 2023, 50 (9):  540-543.  doi: 10.3760/cma.j.cn371439-20230506-00103 Abstract ( 78 )   HTML ( 6 )   PDF (695KB) ( 27 )   Save Long non-coding RNA （lncRNA） is a class of highly conserved transcript with a length of more than 200 nucleotides， which is of great significance for the occurrence， development， diagnosis and treatment of malignant tumors. The abnormal expression of linc01410 in malignant tumors can affect the occurrence and development of malignant tumors by regulating the biological processes such as proliferation， migration and epithelial-mesenchymal transformation of malignant tumor cells， acting on related signaling pathways such as nuclear factor-κB and Notch or through exosome pathways. References | Related Articles | Metrics

Role of ABRACL in the occurrence and development of malignant tumors Ye Tongtong, Wu Zeyu, Xi Wenyi, Wang Zhiwei, Jiang Xiaochun, Zhao Chenhui 2023, 50 (9):  544-547.  doi: 10.3760/cma.j.cn371439-20230506-00104 Abstract ( 75 )   HTML ( 5 )   PDF (688KB) ( 26 )   Save The ABRACL protein， the regulator of actin and cell motility， belongs to the HSPC280 family， and its conserved hydrophobic groove can interact with other proteins to facilitate actin motility and cellular activity. ABRACL is upregulated in tumor tissues and is closely linked with the proliferation and migration of tumor cells. A deeper understanding of the role of ABRACL in tumorigenesis and development may provide new ideas and insights for ABRACL to prevent or reverse tumor progression. References | Related Articles | Metrics

Application of radiotherapy combined with immunotherapy in the treatment of head and neck squamous cell carcinoma Cui Tenglu, Lyu lu, Sun Pengfei 2023, 50 (9):  548-552.  doi: 10.3760/cma.j.cn371439-20230612-00105 Abstract ( 104 )   HTML ( 15 )   PDF (710KB) ( 34 )   Save Immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma （HNSCC） has shown significant clinical benefit. Some studies have shown that radiotherapy combined with immunotherapy can produce synergistic effects， and several phase Ⅰ/Ⅱ clinical trials have suggested that radiotherapy combined with immunotherapy has good safety and preliminary efficacy benefits in locally advanced HNSCC. However， the timing of combination therapy， the selection of radiotherapy dose/fractionation mode and patients are still unclear. This article further discusses the synergistic mechanism， clinical research status and challenges of radiotherapy combined with immunotherapy in the treatment of HNSCC， aiming to guide the clinical practice and improve the prognosis of HNSCC patients. References | Related Articles | Metrics

Advances in immune checkpoint inhibitors in the treatment of recurrent or metastatic head and neck squamous cell carcinoma Chen Xinyi, Weng Yiming, Wei Jiayan, Wang Jinsong, Peng Min 2023, 50 (9):  553-557.  doi: 10.3760/cma.j.cn371439-20230410-00106 Abstract ( 94 )   HTML ( 8 )   PDF (741KB) ( 26 )   Save With the increasing understanding of the complex interaction between the tumor microenvironment and immune therapy， the role of immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma （HNSCC） has gained significant attention. Immune checkpoint inhibitors targeting programmed death-1 （PD-1） and programmed death-ligand 1 （PD-L1）， cytotoxic T-lymphocyte-associated protein-4 （CTLA-4）， and T cell immunoglobulin domain and mucin domain-3 （TIM-3）， such as pembrolizumab， durvalumab， tremelimumab， ipilimumab， and LY3321367， have been applied in numerous clinical trials as monotherapies and combination therapies for the treatment of recurrent or metastatic HNSCC. Further research into the efficacy and safety of these immune checkpoint inhibitors in clinical trials may provide more effective strategies for the treatment of patients with recurrent or metastatic HNSCC. References | Related Articles | Metrics

Progress of bispecific antibody in the treatment of non-small cell lung cancer Qin Xueqian, Yang Hongyu, Wang Zhen, Wang Mengchao, Zhang Xin 2023, 50 (9):  558-563.  doi: 10.3760/cma.j.cn371439-20230612-00107 Abstract ( 79 )   HTML ( 4 )   PDF (765KB) ( 15 )   Save Bispecific antibody （BsAb） is a new type of highly effective anti-tumor drug that can specifically bind two antigens or epitopes simultaneously or successively. At present， evantuzumab targeting epidermal growth factor receptor （EGFR） and cMET has been approved for the treatment of EGFR ex20ins in locally advanced or metastatic non-small cell lung cancer （NSCLC）. Inhibitors targeting programmed death-ligand 1 （PD-L1） and cytotoxic T lymphocyte antigen-4 （CTLA-4）， programmed death-1 （PD-1） and CTLA-4， PD-L1 and transforming growth factor-β， PD-1 and vascular endothelial growth factor are applied to NSCLC. The treatment of NSCLC is underway， showing good safety and efficacy. Further exploring the research progress of BsAbs in the treatment of NSCLC will provide a new diagnosis and treatment idea for the clinical treatment of NSCLC. References | Related Articles | Metrics

Adverse reactions and risk factors of immune checkpoint inhibitors in the treatment of non-small cell lung cancer Deng Juanjun, Zhao Dayong, Li Miao 2023, 50 (9):  564-568.  doi: 10.3760/cma.j.cn371439-20230404-00108 Abstract ( 63 )   HTML ( 3 )   PDF (744KB) ( 27 )   Save Immune checkpoint inhibitors （ICIs） have been widely used in the treatment of non-small cell lung cancer （NSCLC）. However， ICIs related pneumonia， myocarditis， rash， colitis， nervous system immune-related adverse events （irAEs）， as well as hypothyroidism， ocular irAEs， liver irAEs， etc.， can be generated in the process of use， and some irAEs are even fatal. Systemic inflammatory biomarkers as well as chemotherapy， higher body mass index， epidermal growth factor receptor mutation are risk factors for its occurrence. The common irAEs and risk factors are analyzed in order to improve the clinician's understanding of ICIs. References | Related Articles | Metrics

Advances in targeting FGFR2 for treatment of advanced cholangiocarcinoma Huang Hui, Ding Jianghua 2023, 50 (9):  569-573.  doi: 10.3760/cma.j.cn371439-20230410-00109 Abstract ( 114 )   HTML ( 6 )   PDF (711KB) ( 34 )   Save Fibroblast growth factor receptor （FGFR） 2 gene fusion plays an important role in the pathogenesis of cholangiocarcinoma（CCA）. The method of targeting FGFR2 has been listed as the major therapy for advanced CCA. Adenosine triphosphate （ATP）-competitive FGFR inhibitors， represented by infigratinib and pemigatinib， effectively delay tumor progression and prolong patients survival， and are the first-line drugs for advanced CCA patients with FGFR2 fusion. However， almost all the patients treated with infigratinib eventually develop resistance， which require the combination with other drugs. Futibatinib may serve as a later-line drug for advanced CCA patients with V564F mutation after infigratinib resistance. For the infigratinib-resistant CCA patients harboring aberrant activation of the mitogen-activated protein kinase （MAPK） pathway， combination of the MAPK inhibitor or the heat shock protein 90 inhibitor may be considered as a novel therapeutic option. References | Related Articles | Metrics