Current Opinion in Oncology最新文献

Purpose of review: Smoldering myeloma (SMM) is an asymptomatic precursor condition of multiple myeloma (MM) with a prevalence of about 0.5% in those aged >40 years age. While the current standard of care is active surveillance, there is a growing interest to determine the effectiveness of early intervention in this condition. This review discusses the contemporary trials focussed on treating SMM and the case for additional data in this space.

Recent findings: It is imperative to note that the risk stratification for SMM has constantly evolved over time. A proportion of patients with SLiM-CRAB [≥60% bone marrow plasma cells (BMPCs), free light chain ratio (sFLC-ratio) ≥100, and >1 MRI-defined ≥5 mm focal bony lesion, hypercalcemia, renal insufficiency, anaemia, lytic bone lesions], who were classified as high-risk-SMM in the past, have now been classified as MM, based on the IMWG-2014 diagnostic criteria. Current research on SMM risk stratification is focussed on developing models based on longitudinal trends, rather than single-point measures. Earlier trials were studying disease control strategy, working towards delaying disease progression. As the results were promising, currently, there are more trials utilizing intensive treatment approaches aiming at cure to eradicate disease clone (achieving sustained MRD negativity). Further ongoing trials, are attempting to refine disease control strategy and utilize immunotherapies.

Summary: We need more high-quality evidence in post-SLiM-CRAB SMM cohort to better identify the subset of patients most likely to benefit from early intervention. Treatment approaches should be refined considering patient preferences and maintaining quality of life (QoL).

Purpose of review: CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has transformed outcomes for relapsed/refractory large B-cell lymphoma (LBCL), yet nearly half of treated patients relapse, and toxicities remain frequent. A deeper understanding of response predictors is urgently needed to guide patient selection, treatment optimization, and development of rational combination strategies.

Recent findings: Emerging data reveal that response to CAR-T therapy is shaped by patient-specific, tumor-intrinsic, and treatment-related factors. Clinical variables such as age, performance status, inflammation, and microbiome composition influence efficacy. Tumor burden, disease distribution, histologic subtype, and genomic alterations correlate with resistance. Treatment factors, including bridging strategies, lymphodepletion regimen, and CAR-T product design, affect expansion, persistence, and clinical outcomes. Novel insights from immune profiling, radiomics, and single-cell transcriptomics offer further granularity and predictive potential.

Summary: Predictors of CAR-T response span diverse biological and clinical domains and are increasingly actionable. Integrating multimodal biomarkers into routine workflows can personalize care and improve outcomes. Prospective validation, real-time monitoring, and adaptive trial designs are essential next steps toward precision CAR-T therapy.

Purpose of review: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for noninvasive detection of minimal residual disease (MRD), prognosis, and treatment monitoring in early-stage triple-negative breast cancer (eTNBC), an aggressive subtype with high relapse risk. This review synthesizes the state-of-the-art and the advances in ctDNA technologies and evaluates their clinical relevance across the neoadjuvant, postneoadjuvant, and adjuvant settings.

Recent findings: We highlight the most recent (last 18-24 months) key prospective studies demonstrating ctDNA's potential to predict pathological response and recurrence, emphasizing the prognostic value of the ctDNA dynamics and the implications of persistent positivity. We discuss tumor-informed versus tumor-agnostic assays, address challenges in detecting MRD, and explore future directions, including ultrasensitive detection strategies, novel methylation and machine learning-based approaches, and ctDNA-guided therapeutic interventions.

Summary: Despite encouraging results, the clinical utility of ctDNA remains unproven due to technical limitations, especially in assay sensitivity, timing of testing, and low ctDNA shedding/high relapse rate in early-stage disease. Randomized trials are essential to confirm the role of ctDNA in guiding treatment de-escalation or escalation, ultimately aiming to personalize care and improve outcomes in patients with eTNBC.

Purpose of review: This review aims to summarize the current clinical evidence and future perspectives on the use of antiandrogen therapies in metastatic breast cancer, focusing on hormone receptor-positive and triple-negative subtypes, expressing androgen receptor (AR). We discuss recent clinical trials evaluating AR-targeted agents and explore mechanisms of resistance and novel therapeutic strategies.

Recent findings: Clinical trials of androgen-targeting have shown modest activity in AR-positive metastatic breast cancer, with variable disease control rates and progression-free survival depending on AR expression levels, intrinsic AR-dependency and tumor subtype. Combination therapies targeting AR alongside pathways like CDK4/6 and PI3K/AKT/mTOR appear promising in overcoming therapeutic resistance. New-generation agents, including PROTACs, nonligand-binding domain AR inhibitors and epigenetic modulators offer innovative approaches to target AR signalling.

Summary: Despite encouraging preclinical data, antiandrogen therapies have not demonstrated robust strong clinical efficacy in metastatic, AR-positive breast cancer, and their use in the clinical practice is still very limited. Improved patient selection using validated predictive biomarkers is crucial. Combination regimens and next-generation AR-targeting agents represent the future direction to overcome resistance and optimize therapeutic outcomes in AR-driven breast cancers.

Purpose of review: Recent preclinical studies have demonstrated that gliomas interact with the brain at the synaptic level, influencing tumor progression. These local interactions have broader effects on the brain's structural and functional connectivity. This review summarizes recent findings on how brain-glioma interactions impact the brain connectome and explores their clinical implications.

Recent findings: Glioma progression and brain connectivity are interdependent. Functional connectivity changes in glioma patients are observed across the entire brain and are associated with overall survival. Gliomas tend to develop in highly connected brain hubs, which have higher metabolic demands. Structurally, glioblastoma cells preferentially spread along white matter tracts, with tumours located in regions of dense white matter being linked to shorter survival. Moreover, functional network reorganization in glioma patients correlates with cognitive function and involves widespread areas, including the contralateral hemisphere.

Summary: Measures derived from the brain connectome offer promising prognostic value and deepen our understanding of glioma growth and dissemination mechanisms.

Purpose of review: Measurable residual disease (MRD) is a reliable biomarker measuring the quality of morphological complete remission in acute myeloid leukemia (AML). This review will illustrate the settings where, along with drug development, MRD monitoring is by itself an actionable therapeutic target and represents not only a prognostic marker but a predictive marker of response, prompting a further relevant progress toward personalized medicine.

Recent findings: The double nature of certain biomarkers (e.g. PML/RARA , bcr/abl , FLT3 , IDH1/2 , NPM1 ), useful for MRD monitoring and key actors in AML development, has emerged. The use of targeted drugs (e.g. FLT3 inhibitors, IDH1/2 inhibitors) or drug combination that are particularly active in specific AML subsets (e.g. Azacytidine/Venetoclax in NPM1 mutated AML), has paved the way to clinical trial experimenting maintenance or preemptive treatment driven by MRD persistence or reappearance.

Summary: Accurate and specific MRD monitoring, coupled with the increasing development of targeted drugs, will give to clinicians an extraordinary opportunity to anticipate the treatment of AML relapse in the early phases eventually increasing drug efficacy and long-term outcome of the patients (visual abstract).

Purpose of review: To summarize recent advances and emerging strategies for integrating immunotherapy into the neoadjuvant treatment of patients with hormone receptor (HR)-positive/HER2-negative early breast cancer (eBC). This review explores how combining immune checkpoint inhibitors (ICIs) with standard treatments and/or novel strategies may potentially improve responses and long-term outcomes.

Recent findings: Recent clinical trials have demonstrated that adding ICIs to standard neoadjuvant chemotherapy in HR-positive eBC significantly increases pathological complete response (pCR) rates. However, this benefit should be balanced against an increase in side effects, particularly those immune-mediated. Innovative approaches, such as incorporating radiation therapy to neoadjuvant treatments and ICIs have shown promise in enhancing immune responses, potentially overcoming the lower immunogenicity of luminal-like eBC.

Summary: The integration of immunotherapy into neoadjuvant regimens offers a promising strategy to improve outcomes in HR-positive/HER2-negative eBC. While increased pCR rates are encouraging, further research with longer follow-up is necessary to establish the impact on long-term survival. Optimizing patient selection through robust predictive biomarkers and refining combination strategies will be crucial to maximize clinical benefit while minimizing toxicity.

Purpose of review: Immunotherapy has transformed the management of several malignancies, yet its role in rare breast cancer histologies remains poorly defined due to limited research and few dedicated clinical trials. This review critically assesses current knowledge and emerging opportunities for immunotherapy in these uncommon breast cancer subtypes.

Recent findings: Rare breast cancer histologies exhibit heterogeneous immunogenicity, including variable expression of programmed death-ligand 1 (PD-L1), differing levels of tumor-infiltrating lymphocytes (TILs), and distinct mutational burdens. Recent studies highlight potential immunotherapy responsiveness in metaplastic, invasive lobular, apocrine, and other rare breast cancer types, though predictive biomarkers like PD-L1 and tumor mutational burden (TMB) alone appear insufficient. Currently, only two clinical trials specifically target rare breast cancer histologies, emphasizing significant knowledge gaps.

Summary: The effectiveness of immunotherapy in rare breast cancer histologies remains limited, likely due to inadequate patient selection using current biomarkers such as PD-L1 and TMB. Further research must focus on refining predictive biomarkers to better identify patients likely to from immunotherapy and enhance outcomes in these challenging clinical settings.

Purpose of review: Acute myeloid leukemia (AML) characterized by NPM1 mutations or KMT2A rearrangements depends on abnormal epigenetic programs mediated by menin, a critical scaffold protein for sustaining the expression of oncogenic HOX/MEIS1 genes. Therefore, menin inhibitors have become a promising class of AML treatments.

Recent findings: Early-phase trials have shown that agents such as revumenib, ziftomenib, bleximenib, and enzomenib are active, particularly in relapsed/refractory disease, with 23-48% of patients achieving composite complete remission. However, the durability of single-agent treatment remains limited, and resistance mechanisms, such as MEN1 mutations or transcriptional reprogramming, have been identified. Consequently, combination approaches involving venetoclax, hypomethylating agents, or chemotherapy are being investigated to improve response depth and duration. Recent SAVE, KOMET-007, and cAMeLot-2 trials have demonstrated high overall response rates (68%-100%) and encouraging MRD-negative complete remissions when combining menin inhibitors with venetoclax-based regimens. This has been observed even in patients who have previously received venetoclax. Combinations with intensive chemotherapy (e.g., 7 + 3) in the frontline setting have also yielded high CRc rates (up to 94% in NPM1-mutated AML) without exacerbating toxicity.

Summary: These findings justify the integration of menin inhibitors into the AML therapeutic landscape, and support ongoing randomized trials to confirm their benefit in both frontline and relapse or refractory settings.

Purpose of review: Brain metastases occur in nearly 20% of all patients with cancer, with a rising incidence in recent years, partly due to improved systemic therapies that have prolonged survival. Traditionally managed with local approaches such as surgery, whole-brain radiotherapy (WBRT), or stereotactic radiosurgery (SRT), the therapeutic landscape has been significantly transformed by the advent of targeted therapies, immune checkpoint inhibitors, and antibody-drug-conjugates (ADCs).

Recent findings: While symptomatic lesions often require local treatment, asymptomatic or oligosymptomatic brain metastases - especially in molecularly defined subgroups - may benefit from upfront systemic therapy. Significant intracranial efficacy has been demonstrated in nonsmall cell lung cancer (NSCLC) with oncogenic drivers treated with tyrosine kinase inhibitor (TKIs), in HER2-positive breast cancer with TKIs and ADCs, and in melanoma with dual immune checkpoint blockade or BRAF/MEK inhibitors. While these therapies have substantially improved intracranial disease control, the survival outcomes remain suboptimal and the optimal sequencing or combination of systemic therapy and local treatments such as SRT is yet to be defined. Several ongoing trials are exploring these strategies with promising early results, warranting further investigation.

Summary: The therapeutic landscape of brain metastases has recently been transformed by the emergence of central nervous system (CNS)-penetrant systemic therapies. These advances underscore the need for updated clinical practice guidelines to optimize the overall management of patients with brain metastases.