Expert Review of Anticancer Therapy最新文献

Introduction: Adipokines are bioactive signaling molecules secreted from adipose tissue (AT) that have regulatory functions in maintaining metabolic homeostasis. In physiological conditions, balanced adipokine secretion supports metabolic stability and organ function. However, disruption of this balance can promote chronic inflammation and increase cancer risk. While their role in normal physiology is recognized, biological functions of adipokines in renal cell carcinoma (RCC) remain partially understood.

Areas covered: This review explores the biological functions of key adipokines such as adiponectin, leptin, visfatin, nesfatin-1, apelin, and omentin-1 in normal cellular processes and RCC. A search of the literature on PubMed, Web of Science, and Embase databases was performed from January 2000 through April 2025. This review summarizes findings on how these adipokines influence tumor biology, with a specific focus on their emerging roles in RCC. The review includes new findings and their possible limitations and the complexity of adipokine signaling and their roles in promoting or inhibiting tumorigenesis.

Expert opinion: The current evidence highlights adipokines as promising mediators in RCC biology; however, their mechanisms of action remain unclear. Further mechanistic studies are essential to unravel how adipokines regulate tumor initiation and progression. Without such understanding, the rational design of targeted therapies remains limited.

Introduction: Neuroplasticity is a dynamic process by which the brain reorganizes its structure and function in response to internal and external stimuli. In patients with brain neoplasms, neuroplasticity is crucial for preserving or restoring function, as it enables compensation for the tumor-induced disruption of neuronal circuits. Understanding this adaptive capacity is vital for improving clinical outcomes.

Areas covered: This review examines current research on neuroplasticity in the context of brain tumors. It explores how factors such as tumor location, molecular and genetic profiles, cognitive reserve, and DNA repair capacity influence neural adaptation. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, focusing on studies related to neuroplasticity, connectome analysis, and artificial intelligence (AI) in neuro-oncology. The application of connectomics is discussed as a means to assess brain network reorganization. Furthermore, the integration of AI is analyzed concerning its potential in enhancing diagnostic precision, prognostic models, and individualized treatment strategies.

Expert opinion: The convergence of neuroplasticity research, connectomics, and AI offers promising avenues for advancing personalized neuro-oncology care. Greater understanding of these elements can guide clinicians in developing tailored therapeutic interventions, ultimately improving patient function, prognosis, and quality of life.

Introduction: The tumor microbiome, a diverse microbial community within the tumor microenvironment (TME), significantly influences cancer progression and immunotherapy outcomes in colorectal cancer (CRC). Understanding its role in modulating immune responses and therapeutic resistance is critical for advancing precision oncology.

Areas covered: This review examines the tumor microbiome's impact on CRC immunotherapy, focusing on immune checkpoint inhibitors (ICIs) like anti-PD-1/PD-L1 and anti-CTLA-4. It explores microbial composition, their immune-modulatory mechanisms, and metabolite-driven resistance pathways, including short-chain fatty acids and polyamines. Emerging strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and targeted antibiotics are discussed, alongside challenges in personalizing microbiome-based therapies. Literature was sourced from peer-reviewed studies on tumor microbiome dynamics and immunotherapy resistance.

Expert opinion: The tumor microbiome shapes CRC immunotherapy efficacy by modulating immune evasion and TME dynamics. Targeted interventions like FMT and probiotics show promise in enhancing ICI responses, but challenges include microbial variability, safety concerns, and ethical considerations. Future research should prioritize personalized microbiome profiling and standardized protocols to optimize therapeutic outcomes and overcome resistance in CRC.

Introduction: Oncolytic viruses (OVs) are a promising yet understudied class of therapeutic agents. OVs mediate anti-tumor activity through multiple mechanisms, including direct lysis of tumor cells, local expression of therapeutic transgenes, and induction of anti-tumor immunity. In 2015, Talimogene laherparepvec (T-VEC) was approved OV for melanoma. Recent literature search and real-world experience have highlighted some of the challenges with clinical adoption of OV therapy and identified new opportunities for improving the clinical use of OVs for cancer treatment.

Areas covered: This review provides a brief overview of recent challenges and lessons learned from clinical trials and real-world data related to T-VEC and explores novel strategies for enhancing the therapeutic activity of OVs.

Expert opinion: OVs are versatile agents that can attack cancer at multiple levels. The ability to use OVs to add to defined mechanisms of anti-tumor activity, such as direct tumor cell killing, induction of anti-viral and anti-tumor immune responses, and effective delivery of therapeutic payloads, have resulted in multiple new OVs with promising early clinical data. OVs can be an especially useful tool for developing a more personalized approach to cancer treatment based on unique clinical features of patients and the molecular features of specific tumors.

Background: Research on urothelial carcinoma of the bladder (UCUB) in non-Hispanic Asian American (NHAA) populations typically amalgamate all subgroups, masking significant intra-ethnic difference. This study aimed to examine variations in UCUB characteristics and outcomes within NHAA populations.

Research design and methods: Patients with UCUB were identified from the Surveillance, Epidemiology, and End Results database. The NHAA cohort disaggregated into Chinese, Filipino, South Asian, Japanese, Korean, Vietnamese, and other Asian subgroups. Kaplan-Meier and Cox proportional hazards models were used to estimate unadjusted and adjusted overall survival (OS) and cancer-specific survival (CSS).

Results: NHAA patients (n = 2,686) exhibited the longest median OS (88 months) compared to other cohorts (p < 0.001). Among NHAA subgroups, five-year OS rates ranged from 50% in Filipino patients to 64% in other Asian groups. In adjusted analyses, Chinese (HR 0.84, 95% CI 0.74-0.94), Korean (HR 0.74, 95% CI 0.61-0.91), and other Asian (HR 0.68, 95% CI 0.56-0.82) patients exhibited significantly reduced mortality risk relative to Non-Hispanic White patients.

Conclusions: Filipino Americans faced comparatively poorer survival, while Chinese and Korean Americans showed more favorable prognoses. These findings highlight the need for targeted, culturally tailored interventions and refined risk stratification to enhance equity in the management of UCUB.

Background: Palbociclib is a cornerstone treatment for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer.

Research design and methods: This retrospective cohort study included 140 patients who were resistant to endocrine therapy and received palbociclib in combination with endocrine therapy. It is aimed to evaluate the efficacy and tolerability of palbociclib and to identify factors influencing progression-free survival and overall survival.

Results: A total of 140 were enrolled in the study; 57 and 83 patients were primary and secondary resistance to endocrine therapy, respectively. In the whole cohort, regarding progression-free survival; low Ki-67 and incidence of moderate-to-severe (grade 3/4) neutropenia were associated with longer median progression-free survival with p-values of 0.004 (3.7 vs. 8.4 months) and 0.026 (4.7 vs. 6.5 months), respectively. Regarding overall survival, duration on palbociclib (≥12 months) had longer overall survival compared with patients who received palbociclib <12 months (p = 0.0012). The overall survival was longer in the secondary-resistant group than in the primary-resistant group (log-rank test p = 0.0003).

Conclusion: In a metastatic setting, low Ki-67 and moderate-to-severe neutropenia are associated with better survival outcomes in endocrine resistant patients treated with palbociclib (Clinical trial registration: www.clinicaltrials.gov identifier is NCT06338644).

Background: This subgroup analysis investigates the clinical characteristics, treatment patterns, and outcomes of chronic lymphocytic leukemia (CLL) in the Middle East (ME).

Research design and methods: Retrospective study retrieved medical records of CLL patients treated for ≥12 months (CLL-treated) or treatment-naïve (TN). Results included data from 442 CLL-treated and 123 TN patients across five ME countries.

Results: CLL-treated group mean age: 61.1 ± 11.28 years; TN cohort: 63.5 ± 13.53 years. Most patients in both groups were male. CLL-IPI scores were mostly unavailable in both cohorts. Cytogenetic abnormalities were tested in 20.6% of CLL-treated and 18.7% of TN cohorts, with del(17p) being the most common abnormality (12.4% and 11.4%, respectively). TP53 aberrations were found in 9.0% of CLL-treated and 9.8% of TN cohorts. Regarding first-line treatment, 76.5% received CIT, while 17.9% received targeted therapies, with ibrutinib (75.9%) being the most common. CIT use led to significant resource utilization, including outpatient visits, length of stay, and blood transfusions.

Conclusion: CLL management in the ME is characterized by suboptimal utilization of risk-based treatment and genetic testing despite access to targeted therapy. Poor CLL outcomes stem from reliance on CIT, associated with an unfavorable safety profile and healthcare resource use compared to targeted therapies in the region.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT04964908.

Introduction: Neuroendocrine neoplasms (NENs) of the lung make up a heterogeneous clinicopathologic ensemble, encompassing well-differentiated neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Despite being characterized since decades, they still continue to embody diagnostic and therapeutic challenges, where establishing correlations among tumor nomenclature, molecular alterations, and therapeutic options is essential for the best clinical decision making.

Areas covered: Lung NENs were dissected according to five conveying perspectives (available English literature in PubMed, National Library of Medicine): (i) pathologic and molecular grounds for clinical decision making; (ii) tumor microenvironment and tumor immune microenvironment; (iii) how to manage NETs, especially in the metastatic setting; iv) handling life-threatening NECs, especially in light of emerging therapeutic protocols; (v) radiotherapy with some hints at the surgery's role.

Expert opinion: Diagnosis of NETs and NECs has precise clinical implications, which influences tumor nomenclature and clinical decision making (surgery, chemotherapy, radiotherapy, immuno-oncology). However, unexpected subtypes are currently emerging, which question the traditional segregation of NETs and NECs as separate and non-communicating tumor subsets, with no pathogenetic link. This paradigm shift could not only affect our outlook on lung NENs, but even modify the essence of the patient clinical management.

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of solid tumors. This meta-analysis of randomized controlled trials aimed to assess the survival benefit of anti-PD-1/PD-L1 therapies in women with advanced or recurrent endometrial cancer (EC) and mismatch repair deficiency (dMMR).

Methods: A systematic search was conducted in PubMed, Scopus, Cochrane, and Web of Science databases to compare PD-1/PD-L1 inhibitors versus standard therapy in patients with advanced/recurrent EC. Studies were screened based on predefined inclusion/exclusion criteria. Risk of bias was assessed using the Cochrane Risk of Bias Tool. We used DerSimonian and Laird random-effects models to estimate hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs).

Results: Five studies including 2,739 patients were analyzed, with 627 (22.90%) having dMMR tumors. ICIs significantly improved progression-free survival (HR 0.35; 95% CI 0.28-0.44) and overall survival (HR 0.40; 95% CI 0.28-0.57) in dMMR patients. No significant difference was found in objective response rate (RR 1.72; 95% CI 0.88-3.36).

Conclusions: The addition of immunotherapy for treating patients with advanced or recurrent endometrial cancer with dMMR and high microsatellite instability significantly improved PFS and OS outcomes.

Registration: PROSPERO (CRD22057890200).