Critical reviews in oncology/hematology最新文献

Cellular senescence, a hallmark of aging, has emerged as a captivating area of research in tumor immunology with profound implications for cancer prevention and treatment. In the tumor microenvironment, senescent cells exhibit a dual role, simultaneously hindering tumor development through collaboration with immune cells and evading immune cell attacks by upregulating immunoinhibitory proteins. However, the intricate immune escape mechanism of cellular senescence in the tumor microenvironment remains a subject of intense investigation. Chronic inflammation is exacerbated by cellular senescence through the upregulation of pro-inflammatory factors such as interleukin-1β, thereby augmenting the risk of tumorigenesis. Additionally, the interplay between autophagy and cellular senescence adds another layer of complexity. Autophagy, known to slow down the aging process by reducing p53/p21 levels, may be downregulated by cellular senescence. To harness the therapeutic potential of cellular senescence, targeting its immunological aspects has gained significant attention. Strategies such as immune checkpoint inhibitors and T-cell senescence inhibition are being explored in the context of cellular senescence immunotherapy. In this comprehensive review, we provide a compelling overview of the regulation of cellular senescence and delve into the influencing factors, including chronic inflammation, autophagy, and circadian rhythms, associated with senescence in the tumor microenvironment. We specifically focus on unraveling the enigmatic dual role of cellular senescence in tumor immune escape. By deciphering the intricate nature of cellular senescence in the tumor microenvironment, this review aims to advance our understanding and pave the way for leveraging senescence as a promising target for tumor immunotherapy applications.

There is a much debate regarding optimal selection in patients with metastatic cancer who should undergo local treatment (surgery or radiation treatment) to the primary tumor and/or metastases. Additionally, the optimal treatment of newly diagnosed metastatic cancer is largely unclear. Current prognostication systems to best inform these clinical scenarios are limited, as all metastatic patients are grouped together as having Stage IV disease without further incorporation of patient and disease-specific covariates that significantly impact patient outcomes. Therefore, improving current prognostic scoring systems and incorporation of these covariates is essential to best individualize treatment for patients with metastatic cancer. In this narrative review article, we provide a detailed review of prognostication systems that can be used for both the site of metastasis and primary site to best tailor treatment in these patients. Additionally, we discuss the incorporation and ongoing developments in radiographic, genomic, and biostatistical techniques that can be used as prognostication tools.

Small cell lung cancer (SCLC) remains a challenge in oncology due to its aggressive behavior and dismal prognosis. Despite advances in treatments, novel strategies are urgently needed. Enter liquid biopsy-a game-changer in SCLC management. This revolutionary non-invasive approach allows for the analysis of circulating tumor cells (CTCs), offering insights into tumor behavior and treatment responses. Our review focuses on a groundbreaking frontier: harnessing CTCs to create three-dimensional (3D) organoid models. These models, derived from CTCs that break away from the primary tumor or metastatic locations, hold immense potential for revolutionizing cancer research, especially in SCLC. We explore the essential conditions for successfully establishing CTC-derived organoids-a transformative approach with profound implications for personalized medicine. Our evaluation spans diverse isolation techniques, shedding light on their advantages and limitations. Furthermore, we uncover the critical factors governing the cultivation of 3D organoids from CTCs, meticulously mimicking the tumor microenvironment. This review comprehensively elucidates the molecular characterization of these organoids, showcasing their potential in identifying treatment targets and predicting responses. In essence, our review amalgamates cutting-edge methodologies for isolating CTCs, establishing transformative CTC-derived organoids, and characterizing their molecular landscape. This represents a promising frontier for advancing personalized medicine in the complex realm of SCLC management and holds significant implications for translational research.

Background: In patients with high-risk (HR) prostate cancer (PCa) treated with radiotherapy and androgen deprivation therapy (ADT), intensification with androgen receptor pathway inhibitor (ARPI) improves overall survival (OS), at the cost of significant side-effects. We hypothesized that "augmented RT" schedules (defined as either dose-escalation on the prostate gland over 78 Gy and/or addition of whole pelvic radiotherapy (WPRT)), combined with long-term ADT can reach excellent prostate cancer specific survival (PCSS) in this population with little detrimental impact on quality of life.

Methods: We searched Pubmed database until February 8, 2024. Studies reporting both oncological and toxicity outcomes after "augmented RT" were deemed eligible. Studies without ADT or with ARPI intensification were deemed ineligible.

Results: Dose-escalation within the prostate gland at doses over 78 Gy halved the risk of biochemical recurrence at 5 years, with however no impact on PCSS. The addition of WPRT provides a 5-year disease-free survival (DFS) reaching 89.5 % at 5 years, with no significant increase in late grade≥ 2 genito-urinary (GU) or gastrointestinal (GI) toxicity. Combined approaches result in 9-year PCSS ranging between 96.1 % and 100 %. Most approaches demonstrated excellent safety profiles.

Conclusions: "Augmented RT" reached excellent oncological outcomes, with minimal additional toxicity. The development of biomarkers might lead to further treatment personalization, in the rapidly evolving landscape of systemic therapies.

Small cell lung cancer (SCLC) is a highly aggressive disease, often diagnosed at an advanced stage and with limited treatment options. In recent years, immunotherapy has been approved in combination with chemotherapy in the first line setting of extensive stage disease (ES-SCLC). However, only 10-15 % of patients with ES-SCLC treated with chemoimmunotherapy (CT-IO) experience a long-term benefit. In addition, patients are often clinically frail due to advanced age, comorbidities, and disease-related symptoms, making SCLC a challenging condition. Real-world evidence (RWE) becomes particularly valuable in this scenario, not only to confirm the results of pivotal trials, but also to evaluate the outcomes of CT-IO in populations that are generally excluded from clinical trials. RWE could also define the role of integrative treatments such as thoracic consolidation radiotherapy and prophylactic cranial irradiation, which are used in selected patients in the clinical practice but were scarcely applied in pivotal trials. In this review, we focused on RWE in ES-SCLC, with the aim of improving clinical decision making. Notably, real-world data have largely confirmed the efficacy and safety of CT-IO observed in pivotal clinical trials, with a possible benefit even in more fragile patients. However, these studies also highlight that a significant proportion of the ES-SCLC population remains untreated due to poor clinical conditions.

Tumor metastasis involves a series of complex and coordinated processes, which is the main cause of patient death and still a significant challenge in cancer treatment. Pre-metastatic niches (PMN), a specialized microenvironment that develops in distant organs prior to the arrival of metastatic cancer cells, plays a crucial role in driving tumor metastasis. The development of PMN depends on a complex series of cellular and molecular components including tumor-derived factors, bone marrow-derived cells, resident immune cells, and extracellular matrix. Fibrinogen, a key factor in the typical blood clotting process, is related to tumor metastasis and prognosis, according to a growing body of evidence in recent years. Fibrinogen has emerged as an important factor in mediating the formation of tumor microenvironment. Nevertheless, a clear and detailed mechanism by which fibrinogen promotes tumor metastasis remains unknown. In this review, we first explore the roles of fibrinogen in the development of PMN from four perspectives: immunosuppression, inflammation, angiogenesis, and extracellular matrix remodeling. We highlight the significance of fibrinogen in shaping PMN and discuss its potential therapeutic values, opening new avenues for targeting fibrinogen to prevent or treat metastasis.

Breast cancer remains the most prevalent malignancy among women globally and ranks as the leading cause of cancer-related mortality in this demographic. Approximately 13 %-15 % of all breast cancer cases are classified as HER2-positive, a subtype associated with a particularly unfavorable prognosis. A large number of patients with HER2-positive breast cancer continue to face disease progression after receiving standardized treatment. Given these challenges, a thorough exploration into the mechanisms underlying drug resistance in HER2-targeted therapy is imperative. This review focuses on the factors related to drug resistance in HER2-targeted therapy, including tumor heterogeneity, antibody-binding efficacy, variations in the tumor microenvironment, and abnormalities in signal activation and transmission. Additionally, corresponding strategies to counteract these resistance mechanisms are discussed, to advance therapeutic efficacy and clinical benefits in the management of HER2-positive breast cancer.

Soft tissue sarcomas (STS) represent a large group of rare and ultra-rare tumors distinguished by unique morphological, molecular and clinical features. Patients with such rare cancers are generally underrepresented in clinical trials which has limited the introduction of new treatment options and subsequent improvement of patient outcomes. Preclinical models of STS that recapitulate the human disease can aid progress in identifying new effective treatments. However, due to the rarity of these tumors there are limited STS models available. Here we review the existing preclinical models of STS, including patient-derived cell lines and organoids, patient-derived xenografts and genetically engineered mouse models. We discuss the advantages and disadvantages of the different models and describe to what extent they have aided clinical translation. Finally, we consider what can be done in the future to enhance their predictivity in the preclinical setting.

Liquid biopsy (LB) has revolutionized molecular pathology, offering non-invasive insights into tumor biology. However, widespread adoption is hindered by a lack of standardized protocols, requiring robust quality control and harmonized workflows. Large-scale studies are needed to establish effective standard operating procedures (SOPs), particularly for circulating tumor DNA (ctDNA) assays tailored to different disease stages. The International Society of Liquid Biopsy (ISLB) has addressed these challenges by forming a Quality Control and Accreditation Committee, focused on developing frameworks for pre-analytical, analytical, and interpretive processes. Key priorities include mitigating pre-analytical variability with stringent guidelines for blood handling and ensuring adherence to international standards like ISO 15189 and CLIA/CAP. ISLB emphasizes harmonized methodologies, with advanced techniques like droplet digital PCR and next-generation sequencing requiring unified workflows. Collaboration with global initiatives, including the European Society of Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), and International Liquid Biopsy Standardization Alliance (ILSA), supports the validation of ctDNA testing. These efforts are vital for integrating LB into clinical care, advancing precision oncology, and improving patient outcomes through reliable and standardized applications.

Hepatocellular carcinoma (HCC) presents a formidable challenge in oncology, attributed to its association with chronic liver diseases and global prevalence. The immune microenvironment profoundly influences HCC progression, balancing immune suppression and antitumor responses. The Signal Transducer and Activator of Transcription 3 (STAT3) is central to this equilibrium, orchestrating immune dynamics and intertwining tumor progression with immune evasion mechanisms. Dysregulated STAT3 signaling, activated by various stimuli, including cytokines and growth factors, promotes an immunosuppressive milieu within HCC tumors, fostering tumor survival and proliferation while hindering immune surveillance. Non-coding RNAs and other molecules regulate this process, modulating STAT3 activity and influencing immune cell function. Moreover, therapeutic interventions targeting the STAT3 pathway, alongside advancements in radiotherapy, cancer vaccines, and diabetes-related drugs, offer promising strategies in HCC management. Integrating natural compounds with immunotherapy emerges as a novel approach, leveraging their ability to enhance antitumor immunity and counter immune evasion strategies. Understanding the multifaceted role of STAT3 and its interactions within the immune landscape of HCC is paramount for devising effective therapeutic interventions and improving patient outcomes.