Research progress of protein induced by vitamin K absence or antagonist II in liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common pathologic type of primary liver cancer. Liver transplantation (LT) is a radical strategy for treating patients with early-stage HCC, which may lead to a better prognosis compared to hepatectomy and ablation. However, survival of patients who develop HCC recurrence after LT is short, and early recurrence is the most common cause of death. Thus, efficient biomarkers are also needed in LT to guide precision therapy to improve patient prognosis and 5-year survival. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin that cannot activate coagulation, and it is significantly increased in patients with HCC, obstructive jaundice, and those taking vitamin K antagonists. Over the past decades, substantial progress has been made in the study of PIVKA-II in diagnosing, surveilling, and treating HCC, but its role in LT still needs to be elaborated. In this review, we focused on the role of PIVKA-II as a biomarker in LT for HCC, especially its relationship with clinicopathologic features, early recurrence, long-term survival, and donor-recipient selection.

Erratum: Linc-KILH potentiates Notch1 signaling through inhibiting KRT19 phosphorylation and promotes the malignancy of hepatocellular carcinoma: Erratum.

[This corrects the article DOI: 10.7150/ijbs.52279.].

Toddler with giant omental cyst, profound anemia, and shock: case report and review of the literature.

Giant greater omental cysts with associated massive hemorrhage are rare. We encountered a 16-month-old boy with a four-day history of acute abdominal pain, distension, and paleness. Physical examination revealed a blood pressure of 74/27 mmHg. No well-defined masses were observed on abdominal palpation. The hemoglobin level on admission was 24 g/L. After initial resuscitation and blood transfusion, a computed tomography (CT) scan was performed, revealing a giant cystic mass with an intracystic hemorrhage. The diagnosis was confirmed via exploratory laparotomy, and the cyst, with the attached partial omentum was removed. Pathological findings revealed a simple cyst originating from the greater omentum. The patient recovered uneventfully and remained well during the two-year follow-up period. We reviewed the literature published over the last 27 years on cases of omental cysts to evaluate demographic characteristics, clinical presentations, complications, diagnostic tool options, and surgical approaches.

The value of RACK1 and peripheral blood M2/M1 monocyte ratio on the prognosis of patients with oral squamous cell carcinoma.

This study is to evaluate the effect of receptor for activated c kinase 1 (RACK1) and peripheral blood M2/M1 monocytes ratio on the prognosis of patients with oral squamous cell carcinoma (OSCC). A total of 115 OSCC patients who underwent radical surgery in North China University of Science and Technology Affiliated Hospital from January 2015 to December 2015 were included in the experimental group and 34 healthy individuals after a physical examination during the same period were included in the control group. Cancer and para-cancerous tissues were collected and the relationship between RACK1 and M2/M1 ratio and the prognosis of OSCC patients and its predictive value were analyzed. RACK1, M2/M1 ratio, clinical stages, lymphatic metastasis, recurrence and metastasis were considered independent factors for the prognosis of OSCC patients (p<0.05); In addition, RACK1 and the M2/M1 ratio were proven to be of significant predictive values for the prognosis of OSCC patients (p<0.05). RACK1 and peripheral blood M2/M1 monocytes ratio demonstrate great potential as prognostic predictors of OSCC patients.

Circular RNA in cholangiocarcinoma: A systematic review and bibliometric analysis.

BACKGROUND: Cholangiocarcinoma (CCA) is a common primary liver malignancy with a poor prognosis. Many studies have demonstrated the involvement of circular RNAs (circRNAs) in tumorigenesis and progression. METHODS: Four online databases (PubMed, Web of Science, Embase, and Scopus) were searched on May 04, 2023, for original papers regarding CCA and circRNAs. Bibliometric analysis of included studies was performed on R Studio and GraphPad Prism. RESULTS: Thirty studies were included in the systematic review and bibliometric analysis. The systematic review showed that circRNAs were involved in CCA proliferation, invasion, metastasis, chemotherapy resistance, and other biological processes and were related to the prognosis of patients and many clinicopathological features. Exosomal circRNAs provide a new idea for the early diagnosis of CCA. The bibliometric analysis showed a significant upward trend in the number of studies on CCA and circRNAs. The 30 included papers had 201 authors and were published in 22 English journals. The first paper was published in 2018, and the second paper was the most cited (148 citations). CONCLUSION: This systematic review and bibliometric analysis demonstrates that circRNAs in CCA have not been studied enough. CircRNAs play an important role in the occurrence and progression of CCA. They may become new targets for the diagnosis, treatment, and prognostic monitoring of CCA.

A Novel Nomogram for the Preoperative Prediction of Edmondson-Steiner Grade III-IV in Hepatocellular Carcinoma Patients.

Background: Edmondson-Steiner (E-S) grade is a pathological indicator of the degree of hepatocellular carcinoma (HCC) differentiation, and E-S grade III-IV is a poor prognostic factor for HCC patients. Predicting poorly differentiated HCC has essential significance for clinical decision-making. Although some studies have developed predictive models based on magnetic resonance imaging (MRI) and radiomics, radiomic features that require specific software for analysis are impractical for clinical work. This study aims to develop a novel and user-friendly nomogram model to predict E-S grade III-IV. Patients and Methods: Medical data on patients meeting the inclusion criteria were obtained from the Nanjing Drum Tower Hospital HCC database (January 2020 to December 2022). Univariate analysis was used to screen for risk factors associated with E-S grade III-IV. A novel nomogram was established based on the subsequent multivariate logistic regression analysis. The performance of the established model was evaluated through diagnostic ability, calibration, and clinical benefits. Results: Overall, 240 HCC patients were included in this study. Among them, 103 were highly differentiated (E-S grade I-II) HCC and 137 were poorly differentiated (E-S grade III-IV) HCC. A nomogram model that integrated alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (HCVAb), aspartate aminotransferase to lymphocyte ratio index (ALRI), and macrovascular invasion was established. The novel model had a good diagnostic performance with an area under the curve (AUC) value of 0.763. Meanwhile, the model had a diagnostic accuracy of 72.5%, a sensitivity of 78.1%, and a specificity of 65.1%. The calibration curve showed good calibration of the nomogram model (mean absolute error = 0.043), and the decision curve analysis (DCA) demonstrated that the clinical benefit was provided. Conclusion: Our developed nomogram model could successfully predict E-S grade III-IV in HCC patients, which may be helpful in clinical decision-making.

A decision tree model to predict liver cirrhosis in hepatocellular carcinoma patients: a retrospective study.

Background: The severity of liver cirrhosis in hepatocellular carcinoma (HCC) patients is essential for determining the scope of surgical resection. It also affects the long-term efficacy of systemic anti-tumor therapy and transcatheter arterial chemoembolization (TACE). Non-invasive tools, including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4), and γ-glutamyl transferase to platelet ratio (GPR), are less accurate in predicting cirrhosis in HCC patients. We aimed to build a novel decision tree model to improve diagnostic accuracy of liver cirrhosis. Patients and Methods: The Mann-Whitney U test, χ2 test, and multivariate logistic regression analysis were used to identify independent cirrhosis predictors. A decision tree model was developed using machine learning algorithms in a training cohort of 141 HCC patients. Internal validation was conducted in 99 HCC patients. The diagnostic accuracy and calibration of the established model were evaluated using receiver operating characteristic (ROC) and calibration curves, respectively. Results: Sex and platelet count were identified as independent cirrhosis predictors. A decision tree model integrating imaging-reported cirrhosis, APRI, FIB-4, and GPR was established. The novel model had an excellent diagnostic performance in the training and validation cohorts, with area under the curve (AUC) values of 0.853 and 0.817, respectively. Calibration curves and the Hosmer-Lemeshow test showed good calibration of the novel model. The decision curve analysis (DCA) indicated that the decision tree model could provide a larger net benefit to predict liver cirrhosis. Conclusion: Our developed decision tree model could successfully predict liver cirrhosis in HCC patients, which may be helpful in clinical decision-making.

The XOR-IDH3α axis controls macrophage polarization in hepatocellular carcinoma.

BACKGROUND & AIMS: Tumor-associated macrophages (TAMs) are indispensable in the hepatocellular carcinoma (HCC) tumor microenvironment. Xanthine oxidoreductase (XOR), also known as xanthine dehydrogenase (XDH), participates in purine metabolism, uric acid production, and macrophage polarization to a pro-inflammatory phenotype. However, the role of XOR in HCC-associated TAMs is unclear. METHODS: We evaluated the XOR level in macrophages isolated from HCC tissues and paired adjacent tissues. We established diethylnitrosamine/carbon tetrachloride (CCl4)-induced and orthotopically implanted HCC mouse models using mice with Xdh-specific depletion in the myeloid cell lineage (Xdhf/fLyz2cre) or Kupffer cells (Xdhf/fClec4fcre). We determined metabolic differences using specific methodologies, including metabolomics and metabolic flux. RESULTS: We found that XOR expression was downregulated in HCC TAMs and positively correlated with patient survival, which was strongly related to the characteristics of the tumor microenvironment, especially hypoxia. Using HCC-inflicted mice (Xdhf/fLyz2cre and Xdhf/fClec4fcre), we revealed that XOR loss in monocyte-derived TAMs rather than Kupffer cells promoted their M2 polarization and CD8+ T-cell exhaustion, which exacerbated HCC progression. In addition, the tricarboxylic acid cycle was disturbed, and the generation of α-ketoglutarate was enhanced within XOR-depleted macrophages. XOR inhibited α-ketoglutarate production by interacting with IDH3α catalytic sites (K142 and Q139). The increased IDH3α activity caused increased adenosine and kynurenic acid production in TAMs, which enhanced the immunosuppressive effects of TAMs and CD8+ T cells. CONCLUSIONS: The XOR-IDH3α axis mediates TAM polarization and HCC progression and may be a small-molecule therapeutic or immunotherapeutic target against suppressive HCC TAMs. IMPACT AND IMPLICATIONS: Immunotherapies have been widely applied to the treatment of hepatocellular carcinoma (HCC), but to date they have been associated with unsatisfactory efficacy. The tumor microenvironment of HCC is full of different infiltrating immune cells. Tumor-associated macrophages (TAMs) are vital components in the tumor microenvironment and are involved in HCC progression. Herein, we confirm the downregulation of XOR expression in TAMs isolated from human HCC. The loss of XOR in monocyte-derived macrophages increases IDH3 activity and results in an increase in α-ketoglutarate production, which can promote M2-like polarization. Additionally, XOR-null TAMs derived from monocytes promote CD8+ T-cell exhaustion via the upregulation of immunosuppressive metabolites, including adenosine and kynurenic acid. Given the prevalence and high rate of incidence of HCC and the need for improved therapeutic options for patients, our findings identify potential therapeutic targets that may be further studied to develop improved therapies.

Liquid Biopsy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most deadly neoplasms with a poor prognosis. Due to the significant tumor heterogeneity of HCC, alpha-fetoprotein (AFP) or liver biopsy has not yet met the clinical needs in terms of early diagnosis or determining prognosis. In recent years, liquid biopsy techniques that analyze tumor by-products released into the circulation have shown great potential. Its ability to monitor tumors in real time and respond to their global characteristics is expected to improve the management of HCC patients clinically. This review discusses some of the findings of a liquid biopsy in terms of diagnosis and prognosis of HCC.

Conversion therapy for massive hepatocellular carcinoma: A case report and literature review.

Key Clinical Message: For potentially resectable HCC, a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used. Abstract: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. The best treatment for HCC is radical surgical resection, but 70%-80% of patients are ineligible for surgery. Although conversion therapy is an established treatment strategy for various solid tumors, there is no uniform protocol for treating HCC. In this case, we present a 69-year-old male patient diagnosed with massive HCC with Barcelona clinical liver cancer (BCLC) stage B. Because of the insufficient volume of the future liver remnant, we believed radical surgical resection was temporarily impossible. Therefore, the patient received conversion therapy, including four cycles of transcatheter arterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC-Folfox), lenvatinib (8 mg orally once a day), and tislelizumab (an anti-PD-1 antibody, 200 mg intravenously once every 3 weeks). Fortunately, the patient achieved a good treatment response (smaller lesions and improved liver function) and underwent radical surgery finally. There was no clinical evidence of recurrence at 6 months of follow-up. For potentially resectable HCC, this case reveals that a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used.

Targeted pharmacologic inhibition of S-phase kinase-associated protein 2 (SKP2) mediated cell cycle regulation in lung and other RB-Related cancers: A brief review of current status and future prospects.

Small cell lung cancer (SCLC) often exhibits Rb deficiency, TRß and p130 deletion, and SKP2 amplification, suggesting TRß inactivation and SKP2 activation. It is reported that SKP2 targeted therapy is effective in some cancers in vitro and in vivo, but it is not reported for the treatment of SCLC and retinoblastoma. SKP2 is the synthetic lethal gene in SCLC and retinoblastoma, so SKP2 can be used for targeted therapy in SCLC and retinoblastoma. RB1 knockout mice develop several kinds of tumors, but Rb1 and SKP2 double knockout mice are healthy, suggesting that SKP2 targeted therapy may have significant effects on Rb deficient cancers with less side effects, and if successful in SCLC and retinoblastoma in vitro and in animal model, such compounds may be promising for the clinical treatment of SCLC, retinoblastoma, and variety of Rb deficient cancers. Previously our studies showed that retinoblastomas exhibit retinal cone precursor properties and depend on cone-specific thyroid hormone receptor ß2 (TRß2) and SKP2 signaling. In this study, we sought to suppress SCLC and retinoblastoma cell growth by SKP2 inhibitors as a prelude to targeted therapy in vitro and in vivo. We knocked down TRß2 and SKP2 or over-expressed p27 in SCLC and retinoblastoma cell lines to investigate SKP2 and p27 signaling alterations. The SCLC cell lines H209 as well as retinoblastoma cell lines Y79, WERI, and RB177 were treated with SKP2 inhibitor C1 at different concentrations, following which Western blotting, Immunostaining, and cell cycle kinetics studies were performed to study SKP2 and p27 expression ubiquitination, to determine impact on cell cycle regulation and growth inhibition. TRß2 knockdown in Y79, RB177 and H209 caused SKP2 downregulation and degradation, p27 up-regulation, and S phase arrest, whereas, SKP2 knockdown or p27 over-expression caused p27 accumulation and G1-S phase arrest. In the cell lines Y79, WERI, RB177, and H209 treatment with C1 caused SKP2 ubiquitination and degradation, p27 de-ubiquitination and accumulation, and cell growth arrest. SKP2 inhibitor C1 significantly suppressed retinoblastoma as well as SCLC cell growth by SKP2 degradation and p27 accumulation. In vivo study also showed inhibition of tumor growth with C1 treatment. Potential limitations of the success of such a therapeutic approach and its translational application in human primary tumors, and alternative approaches to overcome such limitations are briefly discussed for the treatment of retinoblastoma, SCLC and other RB-related cancers.

Asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis: A preliminary study.

Background: Anastomotic leakage is a life-threatening complication. Improvement of the anastomosis technique is needed, especially in patients with an inflamed edematous intestine. The aim of our study was to evaluate the safety and efficacy of an asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis in pediatric patients. Methods: A total of 23 patients underwent intestinal anastomosis at the Department of Pediatric Surgery of Binzhou Medical University Hospital. Demographic characteristics, laboratory parameters, anastomosis time, duration of nasogastric tube placement, day of first postoperative bowel movement, complications, and length of hospital stay were statistically analyzed. The follow-up was conducted for 3-6 months after discharge. Results: Patients were divided into two groups: the single-layer asymmetric figure-of-eight suture technique (group 1) and the traditional suture technique (group 2). Body mass index in group 1 was lower than in group 2 (14.43 ± 3.23 vs. 19.38 ± 6.74; P = 0.036). The mean intestine anastomosis time in group 1 (18.83 ± 0.83 min) was less than that in group 2 (22.70 ± 4.11 min; P = 0.005). Patients in group 1 had an earlier first postoperative bowel movement (2.17 ± 0.72 vs. 2.80 ± 0.42; P = 0.023). The duration of nasogastric tube placement in group 1 was shorter than that in group 2 (4.12 ± 1.42 vs. 5.60 ± 1.57; P = 0.043). There was no significant difference in laboratory variables, complication occurrence, and length of hospital stay between the two groups. Conclusion: The asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis was feasible and effective. More studies are needed to compare the novel technique with the traditional single-layer suture.

Contrast-enhanced CT findings-based model to predict MVI in patients with hepatocellular carcinoma.

BACKGROUND: Microvascular invasion (MVI) is important in early recurrence and leads to poor overall survival (OS) in hepatocellular carcinoma (HCC). A number of studies have reported independent risk factors for MVI. In this retrospective study, we designed to develop a preoperative model for predicting the presence of MVI in HCC patients to help surgeons in their surgical decision-making and improve patient management. PATIENTS AND METHODS: We developed a predictive model based on a nomogram in a training cohort of 225 HCC patients. We analyzed patients' clinical information, laboratory examinations, and imaging features from contrast-enhanced CT. Mann-Whitney U test and multiple logistic regression analysis were used to confirm independent risk factors and develop the predictive model. Internal and external validation was performed on 75 and 77 HCC patients, respectively. Moreover, the diagnostic performance of our model was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In the training cohort, maximum tumor diameter (> 50 mm), tumor margin, direct bilirubin (> 2.7 µmol/L), and AFP (> 360.7 ng/mL) were confirmed as independent risk factors for MVI. In the internal and external validation cohort, the developed nomogram model demonstrated good diagnostic ability for MVI with an area under the curve (AUC) of 0.723 and 0.829, respectively. CONCLUSION: Based on routine clinical examinations, which may be helpful for clinical decision-making, we have developed a nomogram model that can successfully assess the risk of MVI in HCC patients preoperatively. When predicting HCC patients with a high risk of MVI, the surgeons may perform an anatomical or wide-margin hepatectomy on the patient.

Identification of TLN1 as a prognostic biomarker to effect cell proliferation and differentiation in acute myeloid leukemia.

The protein Talin1 encoded by the TLN1 gene is a focal adhesion-related protein that binds to various cytoskeletal proteins and plays an important role in cell adhesion and movement. Recent studies have shown that it is overexpressed in prostate cancer, liver cancer, and oral squamous cell carcinoma, and is closely related to tumor progression and metastasis. This study integrated bioinformatics and functional analysis to reveal the prognosis and potential functions of TLN1 in AML. The results showed that the expression level of TLN1 was abnormally increased in AML and localized in the cell membrane and cytoplasm, and TLN1 is a significant prognostic indicator of overall survival (OS). Enrichment analysis of related genes showed that TLN1 is related to neutrophil mediated immunity, neutrophil activation and may regulate important signal pathways in hematological tumors including tyrosine kinase receptor, FLT3 and PIK3/AKT. The PPI network shows that TLN1 and MYH9 may be involved in the process of AML tumors together with PIP5K1C, ROCK1, S100A4, MY01A and WAC. Immune infiltration analysis explains that TLN1 is associated with multiple immune cells and may be an important immune marker in AML. Furthermore, molecular biology experiments confirmed that TLN1 is related to the proliferation, differentiation and cycle of AML cells. Silencing TLN1 can inhibit the proliferation of AML cells and promote differentiation through the Talin1/P-AKT/CREB signaling pathway.

Radiomics Analysis on Noncontrast CT for Distinguishing Hepatic Hemangioma (HH) and Hepatocellular Carcinoma (HCC).

Background: To form a radiomic model on the basis of noncontrast computed tomography (CT) to distinguish hepatic hemangioma (HH) and hepatocellular carcinoma (HCC). Methods: In this retrospective study, a total of 110 patients were reviewed, including 72 HCC and 38 HH. We accomplished feature selection with the least absolute shrinkage and operator (LASSO) and built a radiomics signature. Another improved model (radiomics index) was established using forward conditional multivariate logistic regression. Both models were tested in an internal validation group (38 HCC and 21 HH). Results: The radiomic signature we built including 5 radiomic features demonstrated significant differences between the hepatic HH and HCC groups (P < 0.05). The improved model demonstrated a higher net benefit based on only 2 radiomic features. In the validation group, radiomics signature and radiomics index achieved great diagnostic performance with AUC values of 0.716 (95% confidence interval (CI): 0.581, 0.850) and 0.870 (95% CI: 0.782, 0.957), respectively. Conclusions: Our developed radiomics-based model can successfully distinguish HH and HCC patients, which can help clinical decision-making with lower cost.

Classification of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Based on Radiomic Analysis.

INTRODUCTION: Considering the narrow window of surgery, early diagnosis of liver cancer is still a fundamental issue to explore. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICCA) are considered as two different types of liver cancer because of their distinct pathogenesis, pathological features, prognosis, and responses to adjuvant therapies. Qualitative analysis of image is not enough to make a discrimination of liver cancer, especially early-stage HCC or ICCA. METHODS: This retrospective study developed a radiomic-based model in a training cohort of 122 patients. Radiomic features were extracted from computed tomography (CT) scans. Feature selection was operated with the least absolute shrinkage and operator (LASSO) logistic method. The support vector machine (SVM) was selected to build a model. An internal validation was conducted in 89 patients. RESULTS: In the training set, the AUC of the evaluation of the radiomics was 0.855 higher than for radiologists at 0.689. In the valuation cohorts, the AUC of the evaluation was 0.847 and the validation was 0.659, which indicated that the established model has a significantly better performance in distinguishing the HCC from ICCA. CONCLUSION: We developed a radiomic diagnosis model based on CT image that can quickly distinguish HCC from ICCA, which may facilitate the differential diagnosis of HCC and ICCA in the future.

The use of carcinoembryonic antigen levels to predict lung nodule malignancy: a meta-analysis.

OBJECTIVES: To assess the diagnostic value of serum carcinoembryonic antigen (CEA) as a diagnostic biomarker that can be used to differentiate between benign and malignant lung nodules (LNs). METHODS: PubMed, Cochrane Library, and Embase were reviewed from January 2000 to April 2020 for eligible studies. Stata v12.0 was used to conduct this meta-analysis. RESULTS: Our initial literature search identified 511 potentially relevant studies, of which 11 were ultimately included in the present meta-analysis. Ten studies were retrospective and only 1 study was prospective. Overall these studies incorporated 2760 patients and 2760 total LNs (1733 malignant, 1027 benign). Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) values for these studies were 0.33 (95% CI: 0.20-0.49), 0.92 (95% CI: 0.85-0.96), 3.96 (95% CI: 2.84-5.54), 0.73 (95% CI: 0.62-0.87), and 5.42 (95% CI: 3.77-7.78), respectively. The area under curve (AUC) value was 0.77, consistent with moderate diagnostic accuracy. We detected significant heterogeneity when calculating pooled sensitivity (I2 = 95.9%, P = 0.00), specificity (I2 = 92.0%, P = 0.00), PLR (I2 = 61.7%, P = 0.00), NLR (I2 = 92.8%, P = 0.00), and DOR (I2 = 93.8%, P = 0.00). No significant evidence of publication bias was detected via Deeks' funnel plot asymmetry test (P = 0.371). Meta-regression analysis revealed different reference standards to be closely associated with both sensitivity and specificity. CONCLUSIONS: Serum CEA can achieve moderate diagnostic performance as a means of differentiating between malignant and benign LNs.

Research Status, Synthesis and Clinical Application of Recently Marketed and Clinical BCR-ABL Inhibitors.

Tyrosine kinases expressed by BCR-ABL fusion genes can cause changes in cell proliferation, adhesion, and survival properties, which are the main causes of chronic myelogenous leukemia (CML). Inhibiting the activity of BCR-ABL tyrosine kinase has become one of the effective methods for the treatment of chronic myelogenous leukemia. Initially, imatinib was the first small molecule of BCR-ABL tyrosine kinases inhibitors (TKIs) for the effective treatment of chronic myelogenous leukemia. Later, due to the emergence of various BCR-ABL mutations, especially T315I mutation, imatinib developed strong resistance. The second-generation kinase inhibitors dasatinib and nilotinib were able to overcome most of the mutation resistance but not T315I mutations. Therefore, in order to further overcome the problem of drug resistance, new types of KTIs such as flumatinib and radotinib have been developed, providing more options for clinical treatment. Some new drugs have entered clinical trials. In this review, two new BCRABL inhibitors (flumatinib and radotinib) and five new BCR-ABL inhibitors have been introduced into the clinical market in recent years. We reviewed their research status, synthesis methods, and clinical applications.