From macroautophagy to mitophagy: Unveiling the hidden role of mitophagy in gastrointestinal disorders.

In this editorial, we comment on an article titled "Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases", which was published in a recent issue of the World Journal of Gastroenterology. We focused on the statement that "autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal cells". With advancing research, autophagy, and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system, has garnered extensive study. However, the significance of mitophagy, a unique selective autophagy pathway with ubiquitin-dependent and independent variants, should not be overlooked. In recent decades, mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases, especially inflammatory bowel disease, gastric cancer, and colorectal cancer. The interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms, as well as for the development of novel treatment strategies. Exploring the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been exploring. This article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.

Pathological Mechanism and Treatment of Calcified Aortic Stenosis.

Calcified aortic stenosis (AS) is one of the most common valvular heart diseases worldwide, characterized by progressive fibrocalcific remodeling and thickening of the leaflets, which ultimately leads to obstruction of blood flow. Its pathobiology is an active and complicated process, involving endothelial cell dysfunction, lipoprotein deposition and oxidation, chronic inflammation, phenotypic transformation of valve interstitial cells, neovascularization, and intravalvular hemorrhage. To date, no targeted drug has been proven to slow down or prevent disease progression. Aortic valve replacement is still the optimal treatment of AS. This article reviews the etiology, diagnosis, and management of calcified aortic stenosis and proposes novel potential therapeutic targets.

Cinnamaldehyde Regulates the Migration and Apoptosis of Gastric Cancer Cells by Inhibiting the Jak2/Stat3 Pathway.

OBJECTIVE: Gastric cancer is a malignant tumor with high morbidity and mortality all around the world. Because of its poor prognosis and low survival rate, the treatment of gastric cancer has received extensive attention. Cinnamaldehyde (CA) is the main single active component of the Chinese herbal medicine cinnamon, which has a variety of pharmacological effects. The inhibitory effect of CA on the growth of some tumor cells has been proven, but its therapeutic effect on gastric cancer has rarely been reported. METHODS: Through network pharmacology, bioinformatics methods, and molecular docking technology, we predicted the interaction targets of CA and gastric cancer. Moreover, we found that apoptosis is an important mode of action of CA on gastric cancer cells. Subsequently, we validated it in gastric cancer cell lines cultured in vitro. RESULTS: The results showed that in the presence of CA, the Jak2/Stat3 pathway was inhibited, the ratio of Bcl-2/Bax decreased, and the apoptosis of gastric cancer cells was promoted in a concentration-dependent. CONCLUSION: In conclusion, CA can promote the apoptosis of gastric cancer cells by inhibiting the activity of the Jak2/Stat3 pathway, which may achieve the effect of treating gastric cancer.

NSPCs-ES: mechanisms and functional impact on central nervous system diseases.

Patients with central neuronal damage may suffer severe consequences, but effective therapies remain unclear. Previous research has established the transplantation of neural stem cells that generate new neurons to replace damaged ones. In a new field of scientific research, the extracellular secretion of NPSCs (NSPCs-ES) has been identified as an alternative to current chemical drugs. Many preclinical studies have shown that NSPCs-ES are effective in models of various central nervous system diseases (CNS) injuries, from maintaining functional structures at the cellular level to providing anti-inflammatory functions at the molecular level, as well as improving memory and motor functions, reducing apoptosis in neurons, and mediating multiple signaling pathways. The NSPC-ES can travel to the damaged tissue and exert a broad range of therapeutic effects by supporting and nourishing damaged neurons. However, gene editing and cell engineering techniques have recently improved therapeutic efficacy by modifying NSPCs-ES. Consequently, future research and application of NSPCs-ES may provide a novel strategy for the treatment of CNS diseases in the future. In this review, we summarize the current progress on these aspects.

Identification of chronic non-atrophic gastritis and intestinal metaplasia stages in the Correa's cascade through machine learning analyses of SERS spectral signature of non-invasively-collected human gastric fluid samples.

The progression of gastric cancer involves a complex multi-stage process, with gastroscopy and biopsy being the standard procedures for diagnosing gastric diseases. This study introduces an innovative non-invasive approach to differentiate gastric disease stage using gastric fluid samples through machine-learning-assisted surface-enhanced Raman spectroscopy (SERS). This method effectively identifies different stages of gastric lesions. The XGBoost algorithm demonstrates the highest accuracy of 96.88% and 91.67%, respectively, in distinguishing chronic non-atrophic gastritis from intestinal metaplasia and different subtypes of gastritis (mild, moderate, and severe). Through blinded testing validation, the model can achieve more than 80% accuracy. These findings offer new possibilities for rapid, cost-effective, and minimally invasive diagnosis of gastric diseases.

Safety, efficacy, and survival outcomes of immune checkpoint inhibitors rechallenge in patients with cancer: a systematic review and meta-analysis.

BACKGROUNDS: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05). CONCLUSION: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.

Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.

Vinorelbine administration impedes the timely progression of meiotic maturation and induces aneuploidy in mouse oocytes.

Vinorelbine is a commonly used drug to treat various malignancies, such as breast cancer, non-small cell lung cancer, and metastatic pleural mesothelioma. Its side effects include severe neutropenia, local phlebitis, gastrointestinal reactions, and neurotoxicity. In view of the scarcity of research on vinorelbine's reproductive toxicity, this study evaluated the impact of vinorelbine ditartrate, a commonly used form of vinorelbine, on oocyte maturation in vitro. Our investigation revealed that vinorelbine ditartrate had no effect on oocyte meiotic resumption. However, it did reduce the rate of first polar body extrusion, suggesting that it could significantly impede the meiotic maturation of oocytes. Vinorelbine ditartrate exposure was found to disturb the regular spindle assembly and chromosome alignment, leading to the continuous activation of the spindle assembly checkpoint (SAC) and a delayed activation of the anaphase-promoting complex/cyclosome (APC/C), ultimately causing aneuploidy in oocytes. Consequently, the administration of vinorelbine is likely to result in oocyte aneuploidy, which can be helpful in providing a drug reference and fertility guidance in a clinical context.

Multicenter propensity score-matched analysis to compare perioperative morbidity after laparoscopic or robotic complex hepatectomy for solitary hepatocellular carcinoma.

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.

Nuclear matrix protein 22 in bladder cancer.

Bladder cancer (BC) is ranked as the ninth most common malignancy worldwide, with approximately 570,000 new cases reported annually and over 200,000 deaths. Cystoscopy remains the gold standard for the diagnosis of BC, however, its invasiveness, cost, and discomfort have driven the demand for the development of non-invasive, cost-effective alternatives. Nuclear matrix protein 22 (NMP22) is a promising non-invasive diagnostic tool, having received FDA approval. Traditional methods for detecting NMP22 require a laboratory environment equipped with specialized equipment and trained personnel, thus, the development of NMP22 detection devices holds substantial potential for application. In this review, we evaluate the NMP22 sensors developed over the past decade, including electrochemical, colorimetric, and fluorescence biosensors. These sensors have enhanced detection sensitivity and overcome the limitations of existing diagnostic methods. However, many emerging devices exhibit deficiencies that limit their potential clinical use, therefore, we propose how sensor design can be optimized to enhance the likelihood of clinical translation and discuss the future applications of NMP22 as a legacy biomarker, providing insights for the design of new sensors.

Optical enhancement mode 2 improves the detection rate of gastric neoplastic lesion in high-risk populations: A multicenter randomized controlled clinical study.

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

Preoperative Antiviral Therapy and Long-Term Outcomes for Hepatitis B Virus-Related Hepatocellular Carcinoma After Curative Liver Resection: A Multicenter Analysis.

Background & Aims: To examine the association of the history of preoperative antiviral therapy (AVT) with the tumor recurrence and overall survival in HBV-related HCC patients undergoing curative-intent hepatectomy. Methods: Patients who underwent curative-intent hepatectomy for HBV-related HCC between 2014 and 2019 at 4 Chinese hospitals were analyzed. Patients were categorized as having undergone preoperative antiviral therapy (AVT) > 1 year or without antiviral therapy (non-AVT). Patient clinical features, short-term outcomes, overall survival (OS), and time-to-recurrence (TTR) were also compared. Multivariate Cox regression analysis was performed to identify the impact of preoperative AVT on the OS and TTR. Results: Among the 565 patients, 190 (33.6%) underwent continuous AVT > 1 year before surgery. Patients in the non-AVT group were more likely to have worse liver function and more advanced tumor pathological characteristics than those in the AVT group. Postoperative morbidity and mortality rates were comparable between the two groups. Multivariate analyses revealed that a preoperative HBV viral level ≥ 2000 IU/mL was independently associated with poorer TTR (hazard ratio, 1.328; 95% CI, 1.049-1.682) and preoperative AVT was a protective factor for OS (hazard ratio, 0.691; 95% CI, 0.484-0.986). Conclusion: A high preoperative HBV DNA level was an independent risk factor for tumor recurrence. Preoperative AVT > 1 year was associated with better OS and a reduced incidence of tumor recurrence by inhibiting the preoperative level of HBV DNA.

Surgical treatment outcomes of acetabular posterior wall and posterior column fractures using 3D printing technology and individualized custom-made metal plates: a retrospective study.

BACKGROUND: Fractures involving the posterior acetabulum with its rich vascular and neural supply present challenges in trauma orthopedics. This study evaluates the effectiveness of 3D printing technology with the use of custom-made metal plates in the treatment of posterior wall and column acetabular fractures. METHODS: A retrospective analysis included 31 patients undergoing surgical fixation for posterior wall and column fractures of the acetabulum (16 in the 3D printing group, utilizing 3D printing for a 1:1 pelvic model and custom-made plates based on preoperative simulation; 15 in the traditional group, using conventional methods). Surgical and instrument operation times, intraoperative fluoroscopy frequency, intraoperative blood loss, fracture reduction quality, fracture healing time, preoperative and 12-month postoperative pain scores (Numeric Rating Scale, NRS), hip joint function at 6 and 12 months (Harris scores), and complications were compared. RESULTS: The surgical and instrument operation times were significantly shorter in the 3D printing group (p < 0.001). The 3D printing group exhibited significantly lower intraoperative fluoroscopy frequency and blood loss (p = 0.001 and p < 0.001, respectively). No significant differences were observed between the two groups in terms of fracture reduction quality, fracture healing time, preoperative pain scores (NRS scores), and 6-month hip joint function (Harris scores) (p > 0.05). However, at 12 months, hip joint function and pain scores were significantly better in the 3D printing group (p < 0.05). Although the incidence of complications was lower in the 3D printing group (18.8% vs. 33.3%), the difference did not reach statistical significance (p = 0.433). CONCLUSION: Combining 3D printing with individualized custom-made metal plates for acetabular posterior wall and column fractures reduces surgery and instrument time, minimizes intraoperative procedures and blood loss, enhancing long-term hip joint function recovery. CLINICAL TRIAL REGISTRATION: 12/04/2023;Trial Registration No. ChiCTR2300070438; http://www.chictr.org.cn .

Survival benefit from adjuvant TACE combined with Lenvatinib for patients with hepatocellular carcinoma and microvascular invasion after curative hepatectomy.

BACKGROUND AND AIMS: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. METHODS: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. RESULTS: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. CONCLUSION: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.

Precise planning based on 3D-printed dry-laboratory models can reduce perioperative complications of laparoscopic surgery for complex hepatobiliary diseases: a preoperative cohort study.

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.

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OBJECTIVES: To investigate the effect of chaperone-mediated autophagy (CMA) on the damage of mouse microglial BV2 cells induce by unconjugated bilirubin (UCB). METHODS: The BV2 cell experiments were divided into two parts. (1) For the CMA activation experiment: control group (treated with an equal volume of dimethyl sulfoxide), QX77 group (treated with 20 µmol/L QX77 for 24 hours), UCB group (treated with 40 µmol/L UCB for 24 hours), and UCB+QX77 group (treated with both 20 µmol/L QX77 and 40 µmol/L UCB for 24 hours). (2) For the cell transfection experiment: LAMP2A silencing control group (treated with an equal volume of dimethyl sulfoxide), LAMP2A silencing control+UCB group (treated with 40 µmol/L UCB for 24 hours), LAMP2A silencing group (treated with an equal volume of dimethyl sulfoxide), and LAMP2A silencing+UCB group (treated with 40 µmol/L UCB for 24 hours). The cell viability was assessed using the modified MTT method. The expression levels of p65, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and cysteinyl aspartate specific proteinase-1 (caspase-1) were detected by Western blot. The relative mRNA expression levels of the inflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were determined by real-time quantitative polymerase chain reaction. Levels of IL-6 and TNF-α in the cell culture supernatant were measured using ELISA. The co-localization of heat shock cognate protein 70 with p65 and NLRP3 was detected by immunofluorescence. RESULTS: Compared to the UCB group, the cell viability in the UCB+QX77 group increased, and the expression levels of inflammation-related proteins p65, NLRP3, and caspase-1, as well as the mRNA relative expression levels of IL-1ß, IL-6, and TNF-α and levels of IL-6 and TNF-α decreased (P<0.05). Compared to the control group, there was co-localization of heat shock cognate protein 70 with p65 and NLRP3 in both the UCB and UCB+QX77 groups. After silencing the LAMP2A gene, compared to the LAMP2A silencing control+UCB group, the LAMP2A silencing+UCB group showed increased expression levels of inflammation-related proteins p65, NLRP3, and caspase-1, as well as increased mRNA relative expression levels of IL-1ß, IL-6, and TNF-α and levels of IL-6 and TNF-α (P<0.05). CONCLUSIONS: CMA is inhibited in UCB-induced BV2 cell damage, and activating CMA may reduce p65 and NLRP3 protein levels, suppress inflammatory responses, and counteract bilirubin neurotoxicity.

The effect of age, sex, and eastern cooperative oncology group performance status on the efficacy and safety of immune checkpoint inhibitors in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The effect of age, sex, and eastern cooperative oncology group performance status (ECOG PS) on the efficacy and safety of immune checkpoint inhibitor (ICI) therapy among hepatocellular carcinoma (HCC) patients remains elusive. Thus, a meta-analysis was conducted to evaluate whether such effects exist. RESEARCH DESIGN AND METHODS: Eligible studies in PubMed, Embase, and Cochrane Library databases were retrieved. RESULTS: One-hundred-and-eleven studies involving 14,768 HCC patients were included. The findings indicated that the ECOG PS didn't have a significant effect on the ORR and PFS in ICI-treated HCC patients (higher ECOG PS vs. lower ECOG PS: ORR: OR = 0.78, 95%CI = 0.55-1.10; PFS: HR = 1.15, 95%CI = 0.97-1.35), while those patients with a higher ECOG PS may have a worse OS (HR = 1.52, 95% CI = 1.26-1.84). There is no significant evidence of the effect of age (older vs. younger) or sex (males vs. females) on the efficacy of ICI therapy in HCC. CONCLUSION: ICI therapy in HCC should not be restricted strictly to certain patients in age or sex categories, while HCC patients with higher ECOG PS may require closer medication or follow-up strategy during ICI therapy. PROSPERO REGISTRATION: CRD42024518407.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.