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Lenvatinib received its initial approval in 2018 for the treatment of advanced hepatocellular carcinoma. It has since emerged as the preferred first line agent, supported by non-inferiority data from the REFLECT trial. Notably, lenvatinib exhibits a more favorable toxicity profile and a higher response rate compared to sorafenib. Despite the approval of immunotherapy in 2020, specifically the combination of atezolizumab and bevacizumab following the IMbrave150 trial, tyrosine kinase inhibitors remain an indispensable class of agents in the landscape of hepatocellular carcinoma treatment. This comprehensive review delves into various facets of lenvatinib utilization in hepatocellular carcinoma, shedding light on real-world data, addressing challenges, and providing insights into strategies to overcome these obstacles. [ABSTRACT FROM AUTHOR]

Rectal cancer presents significant diagnostic and therapeutic challenges, with neoadjuvant therapy playing a pivotal role in improving resectability and patient outcomes. MRI serves as a critical tool in assessing treatment response. However, differentiating viable tumor tissue from therapy-induced changes on MRI remains a complex task. In this comprehensive review, we explore treatment options for rectal cancer based on resectability status, focusing on the role of MRI in guiding therapeutic decisions. We delve into the nuances of MRI-based evaluation of treatment response following neoadjuvant therapy, paying particular attention to emerging techniques like radiomics. Drawing from our insights based on the literature, we provide essential recommendations for post-neoadjuvant therapy management of rectal cancer, all within the context of MRI-based findings. [ABSTRACT FROM AUTHOR]

This document is a response to a letter regarding a paper titled "Real-World Effectiveness of First-Line Lenvatinib Therapy in Advanced Hepatocellular Carcinoma: Current Insights." The authors address concerns raised by the correspondents and clarify that their paper focused on scenarios where immunotherapy is not a viable option for treating hepatocellular carcinoma (HCC). They acknowledge the toxicity related to lenvatinib but highlight the positive results from the REFLECT trial, which showed non-inferior overall survival and significant improvements in secondary efficacy endpoints compared to sorafenib. The authors also mention that their paper focused on scenarios with contraindications to immunotherapy or as a second-line treatment following immunotherapy. They disagree with the suggestion that non-preplanned analysis or retrospective studies should determine the use of lenvatinib or sorafenib, and they favor lenvatinib based on the REFLECT data. The authors disclose their conflicts of interest. [Extracted from the article]

Background: Recently, markers related to molecular classification were suggested as promising therapeutic targets for treatment and prediction of prognosis in gastric cancer (GC), including c-MET, RhoA, and Claudin-18 (CLDN18). This study aimed to investigate their expression in GC and its correlation with clinicopathological characteristics and survival. Methods: We retrospectively evaluated GC patients who underwent curative gastrectomy. c-MET, RhoA, and CLDN18 were analyzed through immunohistochemistry (IHC), and groups for analysis were determined according to the median values obtained for each marker. Results: Among the 349 GC evaluated, 180 (51.6%), 59 (16.9%), and 61 (17.5%) patients were completely negative for c-MET, RhoA, and CLDN18, respectively. Total gastrectomy, D1 lymphadenectomy, poorly differentiated histology, and greater inflammatory infiltrate were more frequent in the c-MET-negative group. Diffuse type, greater inflammatory infiltrate, and advanced pT and pTNM stage were associated with low-RhoA GC. The venous invasion was more frequent in the low-CLDN18 group. Furthermore, c-MET was positively correlated with RhoA and negatively with CLDN18. HER2 expression was associated with c-MET-positive and high-CLDN18 GC; and loss of E-cadherin expression in c-MET-negative and low-RhoA GC. c-MET-negative and Low-RhoA were significantly associated with worse disease-free survival. Conclusions: c-MET, RhoA, and CLD18 expression occurred frequently in GC. RhoA GC had distinct clinicopathological characteristics related to prognosis. c-MET and RhoA were associated with survival but were not independent predictors of prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Biliary tract cancer (BTC) originates from the biliary epithelium of the small ducts within the liver (intrahepatic cholangiocarcinoma, IHCC), the main ducts of the hilum (extrahepatic cholangiocarcinoma, EHCC), or in the gallbladder (gallbladder cancer, GC). Due to presentation with nonspecific symptoms as well as absence of screening, most patients present with advanced disease and unfavorable prognosis., Areas Covered: The ABC-02 trial established the current first-line chemotherapy with gemcitabine/platinum for advanced BTC in 2010. Since then, multiple therapies have become available exploring different targetable alterations, emphasizing the importance of molecular profiling in all patients with BTC as well as understanding the distinct toxicity profile associated with these therapies. Besides chemotherapy, immunotherapy as well as targeted therapies for FGFR2, IDH1 and HER2 will be discussed in this manuscript. We performed a non-systematic review, largely based on high-quality articles on the topic of interest with no predefined protocol., Expert Opinion: The primary objective of this manuscript is to conduct a thorough review of diverse aspects related to the safety of systemic treatment in BTC. As the benefit of these therapies depends on compliance and/or tolerance, the authors aim to discuss different toxicity profiles and to provide insights into strategies for overcoming them.

Background: The regulation of cancer stem cells (CSCs) is influenced by RNA-binding proteins (RBPs). The present study sought to investigate the role of NOVA2 in the processes of self-renewal, carcinogenesis, and lenvatinib resistance in liver CSCs., Methods: Neuro-oncological ventral antigen 2 (NOVA2) expression in liver CSCs was examined by real-time polymerase chain reaction (PCR). In vitro experiments were used to assess the effects of NOVA2 on liver CSC expansion and lenvatinib resistance., Results: In our study, the expression of the RBP NOVA2 was higher in CSCs. NOVA2 also increased the capacity for self-renewal and carcinogenesis of the liver CSCs via the Wnt pathway. Further, suppressing the Wnt pathway leads to desensitization of the hepatocellular carcinoma (HCC) cells that overexpress NOVA2 to apoptosis caused by lenvatinib. Analyzing patient data confirmed reduced levels of NOVA2 and therefore we speculate that NOVA2 may serve as a potential indicator for response to lenvatinib in patients with HCC. Methyltransferase-like 3 (METTL3) and YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1)-dependent N6-methyladenosine (m 6 A) methylation were linked to upregulation of NOVA2 in HCC. Furthermore, it was shown that the expression of METTL3 was elevated in cellular models of type 2 diabetes mellitus (T2DM)., Conclusions: NOVA2 is involved in the process of liver CSC self-renewal and carcinogenesis. In addition, NOVA2 expression may help identify patients with a higher chance of benefiting from lenvatinib treatment and can be a promising therapeutic target for HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-145/coif). T.B.d.C. received honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme Corp, Astra-Zeneca, MD Health Brasil, and Remedy Health Group, support for attending meetings and travel from Ipsen and A2Bio, and payment for participation in Advisory Board from Ipsen and Moderna. The other authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: The epigenetic regulators of cellular senescence, especially long non-coding RNAs (lncRNAs), remain unclear. The expression levels of lncRNA were previously known to be prognostic indicators for tumors. We hypothesized that lncRNAs regulating cellular senescence could also predict prognosis in patients with hepatocellular carcinoma (HCC) and developed a novel lncRNA predictive signature., Methods: Using RNA sequencing data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database, a co-expression network of senescence-related messenger RNAs (mRNAs) and lncRNAs was constructed. Using univariate Cox regression analysis and a stepwise multiple Cox regression analysis, we constructed a prognostic HCC senescence-related lncRNA signature (HCCSenLncSig). Kaplan-Meier analysis was used to compare the overall survival (OS) of high- and low-risk groups stratified by the HCCSenLncSig. Furthermore, the HCCSenLncSig risk score and other clinical characteristics were included to develop an HCC prognostic nomogram. The accuracy of the model was evaluated by the time dependent receiver operating characteristic (ROC) and calibration curves, respectively., Results: We obtained a prognostic risk model consisting of 8 senescence-related lncRNAs: AL117336.3, AC103760.1, FOXD2-AS1, AC009283.1, AC026401.3, AC021491.4, AC124067.4, and RHPN1-AS1. The HCCSenLncSig high-risk group was associated with poor OS [hazard ratio (HR) =1.125, 95% confidence interval (CI): 1.082-1.169; P<0.001]. The accuracy of the model was further supported by ROC curves (the area under the curve is 0.783, sensitivity of 0.600, and specificity of 0.896 at the cut-off value of 1.447). The HCCSenLncSig was found to be an independent prognostic factor from other clinical factors in both univariate and multivariate Cox regression analyses. The prognostic nomogram shows HCCSenLncSig has a good prognostic effect for survival risk stratification. Finally, we found that a higher number of immunosuppressed Treg cells infiltrate in high-risk patients (P<0.001 compared to low-risk patients), possibly explaining why these patients have a poor prognosis. On the other hand, the expression of immunotherapy markers, such as CD276, PDCD1, and CTLA4, was also up-regulated in the high-risk patients, indicating potential immunotherapy response in these patients., Conclusions: The development of HCCSenLncSig allows us to better predict HCC patients' survival outcomes and disease risk, as well as contribute to the development of novel HCC anti-cancer therapeutic strategies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3348/coif). TBC received support from Astra Zeneca, Bayer, Eli Lilly, Genentech/Roche, Bristol-Myers Squibb, Merck KGaA, Merck Sharp & Dohme, and Astellas. TCZ reports funding support from the National Key Clinical Discipline, the Basic and Applied Basic Research Fund Project of Guangdong Province (No. 2021A1515410004). The other authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background and Objective: Neoadjuvant chemotherapy (NACT) followed by radical surgery represents a treatment option for patients with advanced gastric cancer (GC). This case-control study aimed to evaluate the clinicopathological characteristics and surgical outcomes of GC patients who received NACT, and its impact on survival., Methods: We retrospectively reviewed all patients with GC who underwent gastrectomy. A total of 45 cases with NACT were matched with consecutive 45 patients who underwent upfront gastrectomy for the following characteristics: gender, age, gastrectomy type, lymphadenectomy extent, American Society of Anesthesiologists class, histological type, cT and cN., Results: NACT group had smaller tumors (4.9 vs 6.8 cm P = .006), lower lymphatic invasion rate (40% vs 73.3%, P = .001), lower venous invasion rate (18% vs 46.7%, P = .003) and lower perineural invasion rate (35% vs 77.8%, P < .0001). The ypTNM stage was lower in patients treated with NACT (P < .001). The major postoperative complication (POC) rate was lower in NACT patients (6.7% vs 24.4%, P = .02), as was hospital length of stay (10.8 vs 17 days, P = .005)., Conclusions: NACT allowed nodal and tumor downstaging. In addition, patients who underwent NACT had fewer POC and shorter length of hospital stay., (© 2020 Wiley Periodicals, Inc.)