Expert Review of Anticancer Therapy最新文献

Introduction: Gastric and gastroesophageal adenocarcinomas (GEACs) continue to carry a poor prognosis in most patients. New and exciting therapies have entered the treatment landscape in recent years. Prior to these recent approvals, treatment advances had been limited.

Areas covered: Important treatment decision biomarkers for metastatic GEAC are microsatellite instability-high/deficient mismatch repair, human epidermal growth factor receptor-2, programmed-death ligand 1, and claudin 18.2 expression among others (such as Epstein Barr Virus (EBV) and agnostic biomarkers). Results of these biomarkers drive therapy decisions. Second-line treatment in most cases is less biomarker driven and needs further progress.

Expert opinion: Studies of molecular subsets in GEAC has led to the understanding that these are heterogenous diseases that need to be treated differently. Other biomarkers with targeted therapies are being studied including fibroblast growth factor receptor, trophoblast cell surface antigen-2, and epidermal growth factor receptor. Additionally, epidemiological distinctions are starting to drive therapy such as in EBV in GAC.

Background: The role of angiotensin system inhibitors (ASIs) in modifying the prognosis for patients undergoing pancreatic cancer resection is not yet definitively established. This meta-analysis endeavors to consolidate existing real-world data to provide a robust, evidence-based assessment of their impact on clinical outcomes.

Methods: A meticulous search strategy was devised and executed across PubMed, Embase, and Web of Science databases to retrieve all relevant studies evaluating the prognostic impact of ASIs in patients who have undergone resection for pancreatic cancer. Studies comparing survival outcomes between ASI users and non-users were included in the meta-analysis. Publication bias was assessed using funnel plotand Egger's test. Sensitivity analysis employing the leave-one-out approach was conducted to ensure the robustness and reliability of the pooled estimate.

Results: Seven studies encompassing 8,549 patients were analyzed. The utilization of ASIs was significantly associated with improved overall survival (HR: 0.78; 95%CI: 0.68-0.89) in patients undergoing pancreatic cancer resection. Sensitivity analysis further validated the consistency and stability of the pooled result.

Conclusion: Current clinical evidence suggests that ASIs are associated with improved prognosis in patients who have undergone pancreatic cancer resection. These findings highlight the potential of ASIs as a beneficial adjunctive therapy in the management of resected pancreatic cancer, warranting their consideration in clinical management protocols.

Registration: PROSPERO (identifier: CRD42024580624).

Background: The prognostic impact of renin-angiotensin system inhibitors (RASIs) on ovarian cancer (OC) remains indeterminate. This meta-analysis aims to consolidate real-world data to provide a comprehensive, evidence-based assessment of the association between RASIs use and clinical outcomes in OC patients.

Methods: A meticulous search strategy was devised and executed across PubMed, Scopus, and Embase databases to retrieve all relevant studies evaluating the prognostic impact of RASIs in patients with OC. Studies comparing survival outcomes between RASIs users and non-users were included in the meta-analysis.

Results: A total of six studies, encompassing 11 cohorts and 14,634 patients, were included in the meta-analysis. RASIs use was found to be significantly correlated with enhanced survival (HR: 0.82; 95%CI: 0.72-0.92) in the OC patient population. Subgroup analysis showed that ACEIs use (HR: 0.83, 95% CI: 0.78-0.89) and post-diagnostic RASIs use (HR: 0.77, 95% CI: 0.66-0.90) significantly improved overall survival.

Conclusion: This meta-analysis provides evidence that RASIs are associated with improved prognosis in OC patients. These findings suggest that RASIs may have potential as an adjunctive therapy in the management of OC, warranting further investigation and consideration in clinical management protocols.

Introduction: Histone modifications are crucial epigenetic mechanisms for regulating gene expression. Histone acetyltransferases and deacetylases (HDACs) catalyze histone acetylation, a process that mediates transcription. Over recent decades, studies have demonstrated that targeting histone acetylation can be effective in cancer treatment, leading to the development and approval of several HDAC inhibitors.

Areas covered: A comprehensive literature review was conducted using the PubMed database to identify studies evaluating the anticancer efficacy of approved and novel HDAC inhibitors.

Expert opinion: Accumulating evidence highlights the promising benefits of combining HDAC inhibitors with other anticancer agents. Additionally, HDAC-targeting therapeutics could enhance the sensitivity of cancer cells to chemotherapeutics or targeted tyrosine kinase inhibitors, thereby improving overall treatment outcomes. Future clinical studies must focus on optimizing combination therapies to ensure efficacy while maintaining manageable safety profiles.

Background: Immune checkpoint inhibitors (ICIs) are currently the primary approach for managing NSCLC. However, numerous combination therapies are currently under investigation. Our goal is to investigate the overall efficacy and safety of ICIs and taxane-based chemotherapy.

Methods: We conducted a systematic review and meta-analysis, searching web databases for relevant literature. We limited our eligibility to phase II/III randomized clinical trials involving advanced/metastatic NSCLC patients.

Results: We performed a meta-analysis encompassing nineteen studies derived from sixteen RCTs. For patients with sq-NSCLC PD-L1 ≥ 50%, using ICIs plus taxane significantly improve PFS and OS with HR of 0.58 (95% CI, 0.45-0.74, p < 0.0001) and 0.41 (95% CI, 0.33-0.50, p < 0.00001), respectively. For patients with non-sq NSCLC PD-L1 1-49%, the analysis revealed significant improvement of OS and PFS with HR of 0.64 (95% CI, 0.47-0.88, p = 0.005) and 0.62 (95% CI, 0.47-0.81, p = 0.0004), respectively. For TRAEs of all grades, ICIs plus taxane resulted with no significant difference compared to control group with risk ratio (RR) 1.00 (95% CI 0.99-1.02).

Conclusion: The analysis revealed significant improvement in efficacy of ICIs with taxane in advanced/metastatic NSCLC patients compared with ICI/taxane monotherapy.Registration: PROSPERO (CRD42023447532).

Introduction: The advent of immune-based combinations, primarily leveraging immune checkpoint inhibitors, has revolutionized the therapeutic landscape of hepatocellular carcinoma (HCC). The current scenario features multiple therapies that have shown superiority over tyrosine kinase inhibitors; however, the absence of direct comparisons and validated prognostic biomarkers complicates therapeutic decision-making. Additionally, a significant proportion of patients still exhibit primary or secondary resistance to existing immunotherapies, underscoring the ongoing need for novel therapeutic strategies.

Areas covered: This narrative review discusses current strategies aimed at improving the efficacy of immunotherapy for HCC, focusing on the following aspects: available therapeutic options, identification of prognostic biomarkers, approaches to overcoming resistance (including the development of neoantigen vaccines), and the exploration of adjuvant and neoadjuvant strategies.

Expert opinion: The future of systemic therapies for HCC is likely to be driven by advancements in immunotherapy. Key areas of exploration for the coming years include the discovery of novel checkpoint inhibitors or complementary agents to enhance tumor response when combined with existing treatments, a shift toward neoadjuvant/perioperative trials instead of traditional adjuvant approaches, and the development of personalized neoantigen vaccines.

Introduction: Acute Myeloid Leukemia is a heterogeneous hematological malignancy characterized by the uncontrolled proliferation of abnormal myeloid cells. Besides several other genetic abnormalities developed in AML, FLT3 mutations are significant due to their worse prognostic impacts and therapeutic resistance. As a result, these mutations enable AML cells to develop mechanisms for evading immune surveillance.

Areas covered: This review discusses the ways of immune escape of FLT3-mutated AML cells. A literature search was conducted on PubMed, Scopus, and Web of Science databases, covering articles published between 2010 and 2024 with related keywords. The discussion covers AML cells' downregulation of immune recognition markers, expression of immune checkpoint proteins, and establishment of an immunosuppressive tumor microenvironment. Specific attention is given to small extracellular vesicles and their participation in immune escape. The focus is on exosome-mediated pathways and possible combination therapies.

Expert opinion: FLT3 mutations in AML represent a formidable therapeutic challenge due to their crucial role in immune evasion. Exosomes are major players in these processes. Combination therapies targeting the exosome pathway could significantly improve these patients' immune recognition and overall outcomes. Understanding the underlying mechanisms, including targeted therapies, will be required to transcend existing therapeutic limitations and push newer strategies in treatment.

Small renal masses (SRM), especially those under 7 cm pose significant diagnostic challenges when using conventional imaging (CT/MRI). PET/CT with [⁸⁹Zr]Zr-girentuximab offers a promising alternative in this setting by enabling molecular-level imaging. The ZIRCON trial, a phase 3 multicenter study, evaluated the diagnostic accuracy of [⁸⁹Zr]Zr-girentuximab PET/CT in detecting clear cell renal cell carcinoma (ccRCC) in SRM. A total of 300 patients with indeterminate renal masses received a single intravenous dose of [⁸⁹Zr]Zr-girentuximab, followed by PET/CT imaging 5 days post-injection. Generally, sensitivity and specificity for ccRCC detection were 85.5% and 87.0%, respectively. However, smaller masses (maximum diameter: ≤4 cm) demonstrated strong diagnostic performance, with mean sensitivity and specificity of 85% and 89.5%, respectively. PET positivity was observed exclusively in malignant lesions. Nevertheless, both benign and malignant non-ccRCC tumors are 'cold' at [⁸⁹Zr]Zr-girentuximab, thus differential diagnosis remains an unresolved issue. Despite its strengths, the trial highlights limitations: restricted imaging scope to the abdomen, lack of a cost-effectiveness analysis, concerns over radiation exposure given zirconium-89's 78.4-h half-life, and the daily scheduling of the examination. Only further studies and time will reveal whether the ZIRCON trial's findings will shine like a diamond or remain akin to zircon - brilliant but constrained in value.