Expert Review of Anticancer Therapy最新文献

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, with a low survival rate. TFB2M, a mitochondrial transcription factor, maintains normal mitochondrial function. Its role in LUAD is unclear.

Methods: We analyzed TFB2M expression in LUAD and normal tissues based on TCGA database. GSEA analyzed pathway enrichment. TFB2M-knockdown LUAD and control groups were constructed. Western blot detected levels of mitophagy- and ferroptosis-related proteins with/without mitophagy inhibitor (Mdivi-1, 10 μM). Malondialdehyde, glutathione, 4-hydroxynonenal, reactive oxygen species, and Fe²⁺ levels were measured to evaluate ferroptosis. CCK-8, EdU experiments, and flow cytometry evaluated cell survival. Immunofluorescence detected co-localization of glutathione peroxidase 4 and mitochondrial outer membrane transferase 20. Mitochondrial-specific fluorescent probes evaluated mitochondrial changes. A LUAD xenograft mouse model was constructed, with tumor volume and weight (with/without mitophagy inhibitors, 50 mg/kg) measured. IHC detected TFB2M and ki67 expression.

Results: TFB2M was upregulated (p < 0.05), and enriched in ferroptosis and mitophagy-related pathways. Mitophagy inhibitors reversed the promotion of mitophagy and ferroptosis and the inhibition of cell proliferation conferred by TFB2M knockdown. In animal experiments, they weakened the inhibition of mitophagy and the alleviation of LUAD progression induced by TFB2M knockdown.

Conclusion: TFB2M contributes to ferroptosis resistance in LUAD by suppressing mitophagy.

Introduction: Persistent human papillomavirus (HPV) infection is the causative factor for nearly all high-grade cervical lesions (CIN2/3) and invasive cervical cancers. HPV testing therefore plays a key role in the follow-up of patients treated surgically or managed conservatively.

Areas covered: To optimize HPV testing in follow-up, we identified key clinical scenarios - conservative management of high-grade lesions, surveillance after conization or hysterectomy, post-surgical follow-up of cervical carcinoma, and monitoring after primary radiation therapy. We reviewed the evidence to propose a strategy for integrating HPV testing into follow-up.

Expert opinion: HPV testing shows high sensitivity and nearly 100% negative predictive value after conization for cervical high-grade lesions. Post-surgical HPV status is a more reliable predictor of recurrence than histopathological margin assessment. A negative result identifies patients with very low relapse risk. However, the lifetime risk of recurrent dysplasia remains increased and mainly depends on HPV status. Conversely, after fertility-sparing surgery for T1b cervical cancer, HPV testing alone is insufficient to rule out all recurrences. Its role is also unclear in patients after hysterectomy for invasive cancer and in those whose preinvasive lesions regressed spontaneously.

Background: We aimed to investigate the effect of RAD51 expression on pathological response and survival in gastric cancer patients receiving fluorouracil plus leucovorin, cisplatin and docataxel (FLOT) as neoadjuvant chemotherapy (NACT).

Research design and methods: RAD51 immunohistochemistry staining was performed in the endoscopy biopsies of the patients, and the pathological responses in the surgery of the patients after NACT were evaluated using the Ryan tumor regression score (RTRS).

Results: 89 patients participated in this study. The factors affecting the pathological responses of the patients after NACT were examined, patients with high RAD51 nuclear expression percentage (NEP) responded better to NACT (p = 0.020). RAD51 nuclear expression density (NED) (p = 0.127), age (p = 0.999), sex (p = 0.098), clinical stage (p = 0.540), tumor pathology (p = 0.999) did not affect the pathological response after NACT. Age, gender, clinical stage, tumor pathology, RAD51 NEP or RAD51 NED did not affect DFS or OS. Patients with low RTRS had better DFS (p = 0.001) and OS (p = 0.009) results.

Conclusions: As a result of our study, it was observed that patients with high RAD51 NEP had better pathological responses after NACT.

Introduction: The incidence of intrahepatic cholangiocarcinoma has continued to increase, with dismal rates of overall survival. While upfront surgery remains the mainstay of resectable intrahepatic cholangiocarcinoma, systemic therapy has gained increasing acceptance worldwide, especially for advanced and metastatic cholangiocarcinoma.

Areas covered: In this article, we review the different genetic mutations associated with cholangiocarcinoma, as well as recent advances made in the management of intrahepatic cholangiocarcinoma using therapies that directly target actionable mutations. We also review the clinical trials that led to the approval of these drugs, and the specific indications for their use.

Expert opinion: While significant progress has been made in identifying actionable mutations and developing drugs that target these mutations, several challenges exist in the management of intrahepatic cholangiocarcinoma using these targeted therapies. These challenges include issues with drug resistance, efficacy and cost. Furthermore, enrollment in clinical trials for cholangiocarcinoma is very limited and completed trials often lack the diversity needed to generalize their findings.

Introduction: Radiation-related cognitive decline (RRCD), characterized by a decline in cognitive functioning within domains, such as memory and executive function, is a known potential consequence of cranial radiation. Older adults are disproportionately vulnerable to cognitive side effects of radiation (RT), and there can be significant impacts on quality of life and independence. Various mechanisms underlying the development of RRCD have been proposed but have not been specifically evaluated in older adults.

Areas covered: In this article, we review the studies that have evaluated cognitive effects of cranial radiation in older adults and discuss the mechanisms and factors that may lead to increased vulnerability of RRCD development in older adults.

Expert opinion: The review of the literature is limited by the variety of cognitive outcome measurements used as well as different ages evaluated. However, most studies support increased vulnerability to RRCD in older adults. No studies include geriatric assessment or other measures of biological age. Potential interventions include redefining whether different dose constraints are warranted in the older adult population, evaluating new medication interventions and utilizing radiation techniques that treat smaller volumes. Further research is needed to determine whether there is a corresponding reduction in RRCD.

Background: Inflammation, nutritional status, and cardiovascular health are all correlated withmortality in cancer survivors, yet their combined effect remains unclear.

Research design and methods: We included 2,322 cancer survivors from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 cycles. The Advanced Lung Cancer Inflammation Index (ALI), reflecting inflammatory burden and nutritional status, and Life's Essential 8 (LE8), representing cardiovascular health, were categorized into tertiles and three-level groups, respectively. Survey-weighted multivariable Cox models estimated hazard ratios (HR) with 95% confidence intervals (CI).

Results: In multiple adjusted models, higher ALI was correlated with lower all-cause mortality (HR 0.63; 95% CI 0.47-0.84) and non-cancer mortality (HR 0.55; 95% CI 0.39-0.77). Similarly, elevated LE8 scores were linked to reduced risks of all-cause (HR 0.56; 95% CI 0.33-0.95) and non-cancer mortality (HR 0.39; 95% CI 0.22-0.67). Furthermore, high ALI was correlated with the lowest risk of all-cause mortality (HR, 0.38; 95% CI, 0.17-0.87) and non-cancer mortality (HR, 0.19; 95% CI, 0.06-0.56) death among cancer survivors who were high LE8 score.

Conclusions: High ALI and LE8 together reduce all-cause and non-cancer mortality in cancer survivors, supporting combined nutritional-inflammatory and cardiovascular optimization for longer survival.

Objective: To evaluate the cost-effectiveness of toripalimab combined with chemotherapy for the first-line treatment of extensive-stage small cell lung cancer.

Methods: A partitioned survival model was employed with data sourced from the EXTENTORCH clinical trial and related literature. The simulation period was set to 10 years, with a cycle of 3 weeks, and all cost and utility indicators were adjusted using a 5% annual discount rate. Using QALYs as the main evaluation indicator, ICERs were calculated to compare the economic differences between treatment with TC group and PC group. The reliability of the research results was verified through single-factor sensitivity analysis and probabilistic sensitivity analysis.

Results: From the base analysis indicate that the ICER for the TC group relative to the PC group is $3,151 per QALY, which is significantly lower than the WTP set at three times the 2024 per capita GDP of China. Sensitivity analysis shows that the discount rate, incidence of hematotoxicity in TC group, number of treatment cycles and other parameters have the greatest impact on ICER.

Conclusion: At the current willingness-to-pay threshold for Chinese patients, the combination of toripalimab and chemotherapy demonstrates superior cost-effectiveness compared to traditional chemotherapy.

Introduction: In the era of precision medicine, molecular biomarker testing is increasingly becoming the standard of care for Non-Small Cell Lung Cancer (NSCLC) patients. Tissue and liquid biopsy-based Next-Generation Sequencing (NGS) is now highly recommended.

Areas covered: Different NGS platforms emerged as a cost-effective strategy to perform a massive and parallel sequencing performing higher technical sensitivity than old generation technologies in detecting low abundant alterations in challenging diagnostic samples. NGS systems can detect single nucleotide variants (SNV), small insertions, and deletions (indels), copy number alterations (CNAs) and structural variants (SVs) or gene fusions across selected druggable genes optimizing clinical administration of NSCLC patients. The diagnostic implementation of the most adequate NGS panel depending on several factors that could impact on the clinical utility of the testing assay.

Expert opinion: Promising advanced technologies are emerging as potentially integrative tools in personalized medicine. In this context, multi-omic evaluation including genomic, transcriptomic, fragmentomic and epigenomic signatures are under investigation to significantly modify clinical algorithms of NSCLC patients. On this basis, sequencing strategies may play a pivotal role in the implementation of a new predictive model for cancer diagnosis and prognosis.

Introduction: Patients with advanced/metastatic non-small cell lung cancer (NSCLC) and programmed death ligand-1 (PD-L1) tumor cell expression <1% are difficult to treat, and an optimal treatment strategy for these patients is yet to be defined.

Areas covered: There have been significant advances in immunotherapy for NSCLC in the past decade. This article aims to answer the question of the optimal first-line treatment for patients with advanced/metastatic NSCLC and PD-L1 expression <1%, based on efficacy and safety data from phase 3 studies (published up to 31 December 2024).

Expert opinion: Current evidence from subgroup and exploratory analyses of phase 3 studies and indirect comparisons suggest that PD-1/PD-L1 inhibitors (with or without chemotherapy) combined with a cytotoxic T lymphocyte-associated protein-4 inhibitor or antiangiogenic therapy may provide the highest progression-free survival (PFS) and overall survival (OS) benefits in patients with newly diagnosed advanced/metastatic NSCLC and PD-L1 tumor cell expression <1%. Of these regimens, dual immunotherapy with nivolumab and ipilimumab combined with chemotherapy appeared to offer some advantages in terms of OS, PFS, objective response rates, and duration of response, relative to other treatment approaches. Well-designed, comparative studies are warranted to more definitively determine the best first-line treatment for these patients.