Current Opinion in Oncology最新文献

Purpose of review: Metastatic adenoid cystic carcinoma (ACC) remains a therapeutic challenge with no approved systemic standard of care. This review highlights recent advances in ACC biology and emerging therapeutic strategies that may improve outcomes for patients with advanced disease.

Recent findings: Recent progress in understanding the molecular biology of ACC has led to the investigation of novel systemic therapies. Recent studies have focused on targeted agents and immuno-oncology approaches. VEGFR-targeting tyrosine kinase inhibitors, such as lenvatinib and axitinib, have shown encouraging disease control rates and are now considered standard options. Immunotherapy has demonstrated limited efficacy. New agents targeting oncogenic drivers, such as NOTCH1 mutations and epigenetic regulators like PRMT5, have demonstrated preliminary activity in early-phase clinical trials. Additional strategies, including B7-H4 targeted antibody-drug conjugates, MYB-directed vaccines and degraders, and MDM2 inhibitors for TP53 wild-type tumors, offer strong biological rationale for further development.

Summary: While conventional chemotherapy and immune checkpoint inhibitors remain largely ineffective, advances in ACC biology have driven the development of mechanism-based treatments. Future trials should prioritize biomarker-guided patient selection, rational combinations, and integration of molecular diagnostics to improve outcomes in this indolent but ultimately fatal disease.

Purpose of review: The global rise in obesity, metabolic syndrome (MetS), insulin resistance (IR), and type 2 diabetes mellitus (T2DM) is reshaping the epidemiology of thyroid disorders, particularly thyroid nodular disease and differentiated thyroid cancer (DTC). This review summarizes emerging evidence linking metabolic dysfunction to thyroid nodule growth and tumorigenesis.

Recent findings: Chronic hyperinsulinemia in IR states activates mitogenic pathways, including PI3K/AKT/mechanistic target of rapamycin (mTOR) and MAPK/ERK. These effects are amplified in thyrocytes overexpressing insulin receptor isoform A (INSR-A) and insulin-like growth factor 1 receptor (IGF1R). Dysfunctional adipose tissue further increases risk through enhanced leptin signaling, reduced adiponectin-mediated AMPK activation, and persistent systemic inflammation and oxidative stress. Environmental factors such as endocrine-disrupting chemicals and gut microbiota alterations add additional susceptibility. Clinical evidence supports these mechanistic links: patients with thyroid nodules consistently show higher HOMA-IR values, and large cohort studies identify MetS as an independent predictor of thyroid nodularity. Female-specific susceptibility appears to be mediated by estrogen receptor activity, adipokine profiles, and postmenopausal fat redistribution. Therapeutically, metformin shows promise via AMPK activation and mTOR inhibition, exerting both metabolic and antiproliferative effects, although randomized trials specific to thyroid cancer outcomes remain limited. Concerns about GLP-1 receptor agonists and thyroid safety are largely theoretical; current data suggest their established cardiometabolic benefits may outweigh potential risks.

Summary: Converging epidemiological, molecular, and translational evidence underscores the complex interplay between metabolic dysfunction and thyroid diseases. Integrating metabolic health into prevention, risk stratification, and treatment strategies will be essential for advancing precision management of thyroid nodules and DTC.

Purpose of review: This review illustrates the spectrum of atypical computed tomography (CT) appearances of lung cancer and provides practical guidance for accurate diagnosis and staging.

Recent findings: While most lung cancers show typical CT features, certain subtypes present atypically, mimicking benign conditions or other malignancies. These include pneumonic-type adenocarcinoma, multifocal adenocarcinoma with ground-glass/lepidic features, lung cancer with air lucency, and pulmonary carcinoid tumors. Pneumonic-type adenocarcinoma often resembles infectious pneumonia, requiring careful CT evaluation, and tissue sampling for confirmation. Multifocal ground-glass/lepidic adenocarcinomas, most commonly seen in female never-smokers, are indolent with low metastatic potential. Lung cancers with air lucency, appearing as cysts, cavitary, or bullous lesions, challenge volumetric assessment and may benefit from adapted TNM measurements excluding air-space components. Pulmonary carcinoid tumors show variable imaging features and require tailored staging and management based on their differentiation and spread.

Summary: Accurate recognition of atypical CT manifestations of lung cancer is critical to avoid misinterpretation and inappropriate management. Integrating imaging characteristics with histopathologic and, when applicable, molecular data ensures correct staging and guides personalized therapy.

Purpose of review: Antibody-drug conjugates (ADCs) have emerged as a significant therapeutic class in lung cancer, integrating the target specificity of monoclonal antibodies with the cytotoxic potency of chemotherapeutic agents. This review delineates ADC structure, mechanisms of action, and clinical advancements in nonsmall-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), with a focus on novel bispecific formats to address tumor heterogeneity and therapeutic approaches to overcome resistance mechanisms.

Recent findings: Multiple ADCs have demonstrated significant clinical activity in biomarker-defined patient subsets. The human epidermal growth factor receptor 2 (HER2)-targeted ADC trastuzumab deruxtecan has demonstrated unprecedented efficacy in HER2-mutant NSCLC, resulting in global regulatory approvals. Novel ADC targets such as TROP2, HER3, MET, CEACAM5, integrin β6, DLL3, B7-H3, and SEZ6 are undergoing clinical evaluation. Advancements in payload design, linker stability, and conjugation methodologies have enhanced therapeutic indices. Concurrently, bispecific ADCs are emerging to address challenges posed by intratumoral heterogeneity and antigen-loss-mediated resistance mechanisms.

Summary: ADCs are transforming lung cancer therapy by delivering potent cytotoxics with manageable safety. Next-generation bispecific and biparatopic formats may broaden eligibility, improve tumor penetration, and delay resistance. Incorporating predictive biomarkers and real-time monitoring will be key to their use in earlier disease and to establishing ADCs as a cornerstone of precision oncology.

Purpose of review: The purpose of this review is to summarize the breakthroughs in the systemic treatment of patients with nonsmall cell lung cancer (NSCLC) during the last five decades.

Recent findings: Chemotherapy was established in metastatic, locally advanced and early-stage NSCLC. Tyrosine kinase inhibitors have become standard for palliative and adjuvant therapy in patients with driver mutation-positive NSCLC. Immune checkpoint inhibitors were established in operable, locally advanced and metastatic NSCLC. Antiemetics, hematopoietic growth factors, bisphosphonates and opioids improved palliative care.

Summary: Breakthroughs in the systemic therapy of NSCLC during the last five decades included chemotherapy, targeted therapies, immune checkpoint inhibitors and better supportive care.

Purpose of review: This review focuses on the current role of artificial intelligence (AI) in lung cancer screening, diagnosis and therapy. We also highlight its strengths in improving the accuracy and efficiency of these processes.

Recent findings: We evaluate AI's potential in lung cancer screening and prevention, which involves lung nodules detection and differentiation, risk classification and monitoring, and even combination with liquid biopsy in early detection. Additionally, AI's value in patients' selection and treatment planning during surgery, radiotherapy and systemic therapy has been demonstrated. Ultimately, AI's capability in predicting clinical outcomes and toxicities helps in making more informed decisions regarding treatment strategies.

Summary: Artificial intelligence demonstrates great potential in lung cancer management. Although there are limitations to AI and challenges remain, AI based interventions will play a key role in lung cancer management in future.

Purpose of review: Lung cancer in pregnancy is relatively rare, however, with increasing gestational age, its incidence is likely to increase. Many of the summary recommendations were developed before the advent of targeted therapies and immunotherapy, which represent a significant part of modern lung cancer treatment. The aim of this review is therefore to provide a current perspective on this issue.

Recent findings: In diagnostics, we are replacing PET/computed tomography with MRI. It is necessary to discuss with the patient sensitively whether to continue the pregnancy and if so, whether to choose treatment and what kind. Case reports are described about practically all treatment procedures generally known for lung cancer, but some of them cannot be recommended due to possible risks (bevacizumab, chest irradiation), other should be chosen with great caution (some targeted therapy, immunotherapy). Chemotherapy appears to be relatively safe outside the first trimester of pregnancy. The review also addresses general principles of neonatal delivery in these patients.

Summary: Lung cancer in pregnancy is highly stressful for both the pregnant woman and the treatment team. The benefits and risks of possible treatment options need to be openly discussed and a consensus reached between the patient and the treatment team.

Purpose of review: This review provides the latest update on chimeric antigen receptor (CAR) T-cell therapy in diffuse large B-cell lymphoma (DLBCL), as of April 2025, with a focus on specific patient populations, long-term toxicities, and the optimal sequencing of therapies, particularly in view of emerging treatments such as bispecific antibodies.

Recent findings: Currently, three autologous CAR T-cell therapies targeting CD19 (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) have been approved for third-line treatment of DLBCL, demonstrating durable complete remission rates of up to 40%. More recently, axicabtagene ciloleucel and lisocabtagene maraleucel have been approved for second-line therapy in refractory or early-relapsed DLBCL. Additionally, the emergence of CD20/CD3 bispecific antibodies has expanded therapeutic options for relapsed/refractory DLBCL, raising questions about the optimal sequencing of these therapies. Growing real-world evidence further supports the efficacy of CAR T-cell therapy in specific populations, including elderly patients, patients with transformed indolent B-cell non-Hodgkin lymphoma, and those with Richter's transformation. Finally, extended follow-up periods have allowed for a better characterization of the long-term toxicities associated with CAR T-cell therapy.

Summary: Recent data on CAR T-cell therapy in DLBCL provides valuable insights into its benefits for specific populations, the optimization of treatment sequencing, and the management of long-term toxicities.

Purpose of review: This review evaluates the importance of circulating tumor DNA (ctDNA) as a minimally invasive tool in lymphoma management.

Recent findings: Current literature demonstrates ctDNA's ability to alleviate the shortcomings of standard biopsy and imaging, providing real-time insights into tumor burden, clonal evolution, and treatment resistance. In Hodgkin lymphoma, ctDNA allows for comprehensive genomic profiling and treatment monitoring. In diffuse large B-cell lymphoma (DLBCL), ctDNA correlates with disease burden and is valuable for tracking resistance, especially in CAR T-cell therapy. In rare subtypes like primary central nervous system lymphoma (PCNSL) and intravascular large B-cell lymphoma (IVLBCL), ctDNA enhances diagnostic precision and enables early relapse detection. Even in indolent lymphomas, ctDNA could prove useful in relapse monitoring and risk assessment.

Summary: CtDNA analysis could become a key element in personalized lymphoma management, enabling earlier interventions and tailored treatment strategies. However, future efforts should focus on harmonizing methodologies and validating findings in large-scale trials to allow these techniques to be adopted in routine practice.

Purpose of review: First-line treatment strategies for mantle cell lymphoma (MCL) have greatly improved in recent years. High dose cytarabine, autologous stem cell transplantation for eligible patients and anti-CD20 maintenance therapy for all patients, have contributed to enhanced results, establishing a standard of care with unprecedented long-term outcome. Recently, a growing number of effective options such as Bruton's tyrosine kinase (BTK) inhibitors, combinations of targeted therapies, and immunotherapies, have emerged, leading to confusion regarding the optimal first-line approach.

Recent findings: BTK inhibitors have reshaped MCL treatment landscape, optimizing outcomes and minimizing toxicity. They will now be essential to first-line treatment strategy for young patients, challenging the traditional role of autologous stem cell transplantation. Moreover, targeted therapies have opened new prospects on chemo-free treatments for older patients.

Summary: The variety of treatment options will enable tailoring therapy. Prognostic stratification at diagnosis is crucial, paving the way for personalized treatment. This underscores the need for clear guidelines to navigate the complexities of available therapies and ensure effective treatment selection.