Expert Review of Anticancer Therapy最新文献

Introduction: Autophagy is a highly conservative self-degradative process. Previous research confirmed its importance in cancer pathogenesis. PubMed and Google Scholar databases were searched, analyzing studies on the role of autophagy in the development of multiple myeloma. The manuscript focuses on meta-analyses, case-control studies, and observational studies involving people with multiple myeloma.

Areas covered: This article explores the role of autophagy in the development of MM. Autophagy can either promote or inhibit carcinogenesis. Autophagy is crucial in determining the fate of B cells, either supporting their survival or triggering cell death. Drugs that target autophagy may be the focus of 'molecular targeted therapy.' Autophagy mechanisms potentially effective in MM cells are discussed within the context of the unfolded protein response (UPR), the bone marrow microenvironment (BMME), drug resistance, hypoxia, and DNA repair. The genes and pathways involved in MM cell survival and drug resistance, which could serve as new targets for effective treatment, are highlighted.

Expert opinion: The analysis of autophagy gene expression in MM could be a important factor in the diagnostic process and treatment individualization. The autophagy modulation seems to be a relevant target in oncological therapy, it could limit disease progression and increase the effectiveness of treatment.

Background: The objective of this study is to evaluate the correlation between survival outcomes and renin angiotensin system inhibitors (RASI) use in patients treated nivolmab with metastatic non-small cell lung cancer (mNSCLC).

Methods: This retrospective cohort multicentre study was conducted on patients with mNSCLC patients treated Nivolumab monotherapy as second line therapy. Factors affecting the survival of patients receiving concurrent RASI therapy with nivolumab were analyzed.

Results: 614 patients were included. A total of 288 patients (46.9%) were using concurrent RASI. Patients using RASIs had a median progression free survival (PFS) of 10 months compared to 7 months in non-users. In the multivariate analysis, RASI use (HR: 0.747, 95% CI: 0.594-0.941; p: 0.013) was associated with improved PFS. RASI use was also significantly associated with overall survival (OS), median OS of 20 months in users and 12 months in non-users. In the multivariate analysis, RASI use (HR: 0.600, 95% CI: 0.458-0.787; p < 0.001) was associated with improved OS.

Conclusions: In this multicenter real-world study of patients with mNSCLC receiving second-line nivolumab, concomitant use of RASIs was associated with PFS and OS. The integration of RAS blockade into immunotherapy regimens could represent a promising strategy to enhance treatment efficacy.

Background: Immune checkpoint inhibitors (ICIs) improve survival in solid tumors but can cause immune-related adverse events (irAEs) that often require systemic steroids. The impact of steroid dose and timing on ICI efficacy remains unclear.

Methods: We conducted a single-center retrospective study of 466 patients with metastatic solid tumors treated with ICIs between June 2016 and September 2024. Steroids for irAEs were categorized as high dose (≥1 mg/kg prednisolone-equivalent) or low dose (≤0.5 mg/kg). Overall survival (OS), progression-free survival (PFS), and post-irAE OS/PFS were evaluated.

Results: IrAEs occurred in 182 (39.1%) patients, and 81 (17.4%) received systemic steroids. IrAE occurrence was associated with reduced mortality risk. Among patients with irAEs, steroid use increased mortality (p = 0.035) without significantly affecting PFS. High-dose steroids were linked to worse post-irAE OS (p = 0.002) and PFS (p = 0.034), while low-dose steroids showed no detrimental effect. Early initiation ( < 2 months) of high-dose steroids demonstrated the strongest negative association.

Conclusions: High-dose steroids, particularly when started early, are associated with significantly worse survival after irAEs in metastatic solid tumors. These findings support managing irAEs with the lowest effective steroid dose and encourage exploration of steroid-sparing strategies. Subtype-specific analyses were limited by small sample sizes and should be interpreted cautiously.

Introduction: Acute Myeloid Leukemia (AML) is a challenging blood cancer characterized by a high rate of relapse and often unfavorable outcomes. Immunotherapies can pave the way for a changing paradigm in AML treatment and improve therapeutic outcomes, ultimately leading to a possible cure for this challenging disease. This narrative review aims to summarize the progress of immunotherapy and highlight the future landscape of these measures in the context of AML.

Area covered: By searching English-language literature and querying the PubMed database using pertinent Medical Subject Headings, this review traces the development of AML immunotherapy, from the first antibody-drug conjugate, gemtuzumab ozogamicin, to newer approaches, including other monoclonal antibody formats, immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy, and vaccinations.

Expert review: Although there have been significant advances, the outcomes of both traditional and novel therapies are still unsatisfactory. Immunotherapies could eliminate leukemia stem cells, which contribute to treatment resistance and disease relapse in AML. The positioning of these new therapeutic measures in development within the management algorithm for AML and their precise place in each patient's therapeutic plan are future challenges for enhancing targeted, personalized clinical programs.

Background: This study evaluated the cost-effectiveness of repotrectinib as first-line versus second-line therapy compared with chemotherapy for advanced ROS1 fusion - positive non-small cell lung cancer (NSCLC) from a U.S. healthcare payer perspective.

Methods: A partitioned survival model was developed to estimate lifetime costs and health outcomes for three treatment strategies. Outcomes included costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), using a willingness-to-pay threshold of USD 150,000 per QALY One-way, probabilistic sensitivity analyses and scenario analyses were conducted to assess model uncertainty.

Results: Compared with chemotherapy, first-line repotrectinib yielded an additional 3.61688 QALYs at an incremental cost of $1,529,475, resulting in an ICER of $422,871 per QALY. As second-line therapy, repotrectinib provided 1.69511 additional QALYs at an incremental cost of $1,174,738, yielding an ICER of $693,016 per QALY. Both ICERs exceeded the willingness-to-pay threshold. Drug price and utility values were the main drivers of cost-effectiveness. Scenario analyses showed that reducing the price of repotrectinib to 31.843% of the base-case value lowered the ICER for first-line treatment to the WTP threshold.

Conclusions: Repotrectinib is not cost-effective at current prices, but first-line use is consistently more economically favorable than second-line therapy. Price reductions or shorter treatment durations could improve its cost-effectiveness.

Introduction: Synovial sarcoma (SyS) and myxoid round-cell liposarcoma (MRCL) are rare, aggressive soft tissue sarcomas with poor outcomes at the advanced and metastatic stage. Novel therapeutic strategies are urgently needed. Afamitresgene autoleucel (afami-cel) is the first Food and Drug Administration (FDA)-approved, affinity-enhanced T-cell receptor (TCR) therapy targeting the cancer-testis antigen MAGE-A4 in HLA-A*02-positive patients.

Areas covered: This review summarizes clinical evidence from one early-phase study and the pivotal phase 2 SPEARHEAD-1 trial. Afami-cel achieved objective response rates of 39% in SyS and 25% in MRCL, with durable responses exceeding 11 months in SyS. The safety profile is manageable, with hematological toxicities from lymphodepletion and predominantly low-grade cytokine release syndrome; no treatment-related deaths occurred in SPEARHEAD-1.

Expert opinion: Afami-cel represents a milestone in sarcoma therapy, establishing proof of concept for engineered TCR T-cell therapies in solid tumors. However, challenges remain regarding HLA restriction, tumor microenvironment resistance, manufacturing delays and cost. Future efforts should focus on broadening applicability, optimizing combinations, and ensuring equitable access.

Background: This study aimed to evaluate the clinical characteristics and identify prognostic variables affecting overall survival (OS) in children with undifferentiated embryonal sarcoma of the liver (UESL) using data from the SEER database.

Research design and methods: We performed a retrospective cohort analysis of 101 patients aged ≤19 years diagnosed with UESL between 2000 and 2022 from the SEER database. Kaplan - Meier survival analysis and Cox proportional hazards regression were applied to determine independent prognostic factors. A nomogram was constructed based on significant predictors.

Results: Tumor size, surgical resection, and chemotherapy emerged as independent prognostic factors. Patients with tumors larger than 15 cm had a markedly increased risk of mortality. Surgical resection and chemotherapy were associated with improved survival outcomes. A nomogram incorporating these factors was developed to predict OS. Larger tumor size was linked to higher mortality, whereas chemotherapy significantly reduced death risk.

Conclusions: Tumor size, surgery, and chemotherapy are crucial determinants of survival in pediatric UESL. Surgical intervention combined with chemotherapy appears essential for improving prognosis. Further external validation is warranted to refine treatment strategies.

Introduction: Targeting the DNA damage response (DDR) has emerged as a promising therapeutic strategy in oncology. This review highlights the growing clinical relevance of DDR inhibitors beyond PARP inhibitors, focusing on novel targets, biomarker-driven patient selection, and rational combination strategies.

Areas covered: A comprehensive literature search was conducted using PubMed and ClinicalTrials.gov through May 2025, using terms such as 'DDR inhibitors,' 'synthetic lethality,' and the names of specific DDR targets. This review summarizes preclinical and clinical data on next-generation DDR inhibitors, including agents targeting ATR, ATM, APE1, DNA-PK, WEE1, CHK1/2, CDC7, PLK4, PKMYT1, Polθ, USP1, PARG, WRN, and ALC1. It discusses mechanistic rationale, clinical activity, and safety profiles, with emphasis on combination strategies involving chemotherapy, immunotherapy, radiotherapy, and other DDR agents. Key challenges such as resistance, cumulative toxicity, and the need for predictive biomarkers are also addressed.

Expert opinion: DDR-targeting agents hold significant promise, especially when guided by predictive biomarkers and combined with other therapies. As these agents move into later-phase trials, future development should emphasize biomarker-driven design, toxicity mitigation through dose optimization, and expansion into non-canonical tumor types to maximize clinical impact.

Introduction: Genomic profiling has revolutionized the management of Urothelial carcinomas (UC), particularly in muscle-invasive bladder cancer (MIBC) and metastatic UC, by identifying molecular subtypes and actionable mutations that guide personalized therapies and prognostication.

Areas covered: The integration of genomic profiling in UC, potential prognostic and predictive biomarkers of prognosis, and the current landscape of systemic therapies in UC, including FGFR inhibitors (FGFRi), antibody-drug conjugates (ADC), immune checkpoint inhibitors (ICI), and chemotherapy are discussed herein as a narrative and descriptive review.

Expert opinion: Genomic profiling has advanced our understanding of UC diagnosis and treatment, but its routine clinical use remains limited to confirming biomarkers such as FGFR alterations and HER2 amplification for approved targeted therapies such as erdafitinib, a FGFRi, and trastuzumab deruxtecan, a HER2-directed ADC. Testing for other biomarkers such as PD-L1, tumor mutational burden (TMB), and Nectin-4 can be useful, but not required for the use of ICI and enfortumab vedotin. Circulating tumor DNA (ctDNA) is an emerging tool for monitoring disease and guiding therapy, with trials underway to confirm its clinical utility.

Introduction: Oral squamous cell carcinoma (OSCC) is a heterogeneous malignancy with rapid progression, limited therapeutic options, and poor prognosis. Epigenetic alterations - including DNA methylation, histone modifications, and noncoding RNA (ncRNA) regulation - are key drivers of oncogene activation and tumor suppressor silencing, offering novel therapeutic opportunities.

Areas covered: This review summarizes the major epigenetic mechanisms in OSCC and highlights recent progress in therapeutic agents and molecular targets. In particular, we emphasize ncRNA-based modulators, such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which play crucial roles in epigenetic regulation and represent promising therapeutic candidates. Innovative delivery strategies, including exosome-mediated transfer and nanoparticle formulations, are discussed for their potential to improve treatment specificity and overcome resistance. An updated summary of clinical trials targeting epigenetic regulators in OSCC is also presented, along with possible combination strategies to enhance clinical outcomes.

Expert commentary: Epigenetic therapies hold significant promise for precision treatment of OSCC. Combining targeted agents with advanced delivery systems may accelerate clinical translation, while validated biomarkers could support early detection, risk stratification, and personalized therapy.A literature search was conducted in PubMed and ClinicalTrials.gov from January 2002 to July 2025 to identify high-quality studies on epigenetic therapies in OSCC.