Bulletin du cancer最新文献

Trophoblast cell surface antigen 2 (Trop2) is a transmembrane glycoprotein overexpressed in many epithelial cancers and functions as a critical driver of tumor growth, metastasis, and therapeutic resistance. While Trop2-targeting antibody-drug conjugates (ADCs) such as sacituzumab govitecan have demonstrated clinical success, limitations including off-target toxicity and drug resistance underscore the need for alternative modalities. This review explores recent advances in the development of small molecule inhibitors targeting Trop2, with a focus on structure-based strategies. We summarize the oncogenic signaling mechanisms of Trop2, including regulated intramembrane proteolysis and β-catenin stabilization, and identify key structural domains such as the TY-loop, ND-CD ridge, and intracellular phosphorylation region (Ser303, Lys307, Glu310) as candidate binding pockets. Bruceine D is presented as a case study of a natural Trop2-ICD modulator, supported by docking analyses and structure activity insights. In addition, we examine fragment-based drug discovery, covalent/allosteric inhibition, and AI-guided screening strategies, integrating computational and experimental workflows including CETSA, luciferase assays, and ADMET filtering. Together, these approaches provide a comprehensive framework for the rational design and optimization of next-generation Trop2-targeted small molecule therapeutics.

Objective: There is limited information concerning pediatric neuro-oncology in French-speaking Africa. The aim of this work was to assess the status of this specialty in member institutions of the Franco-African Group of Pediatric Oncology (GFAOP).

Methods: Data pertaining to pediatric brain tumors in the GFAOP registry were analyzed. A short questionnaire was sent to the GFAOP centers to collect information regarding the neuro-oncology activity. Recordings and minutes of the 17 teleconferences that took place between 01/2023 and 03/2025 were reviewed and analyzed.

Results: Only 331 patients were registered between 2016 and 2025. This suggests a considerable gap in terms of diagnosis. Most units manage between one and ten patients annually, with low-grade glioma and medulloblastoma being the most common tumors. In most units, the costs of treatment are borne by families. The review of the minutes of the teleconferences highlights important gaps in knowledge and obvious deficiencies in communication between the different teams involved.

Conclusions: This work highlights the challenges associated with the development of pediatric neuro-oncology in French-speaking Africa. The implementation of multidisciplinary programs is a critical step to improve the care of children with brain tumors.

Metastatic castration-sensitive prostate cancer (mCSPC) has undergone major therapeutic advances with the introduction of next-generation androgen receptor pathway inhibitors (ARPI). Two treatment strategies have demonstrated clinical benefit at this stage: doublet therapy, combining androgen deprivation therapy (ADT) with one of the four currently available ARPI, and triplet therapy, integrating abiraterone or darolutamide with docetaxel. The choice of therapeutic strategy is based on a personalized assessment that considers both tumor aggressiveness and the patient's overall profile, particularly cardiovascular and cognitive comorbidities, regardless of age, frailty, or level of activity. Optimal management of mCSPC requires a multidisciplinary approach, including a baseline cardiovascular workup, systematic geriatric assessment, non-pharmacological interventions (such as tailored physical activity and cognitive stimulation programs), calcium and vitamin D supplementation, structured sexual health support, and a comprehensive medication review conducted in collaboration with a pharmacist. Ongoing trials are exploring treatment de-escalation strategies, notably intermittent ADT, to preserve antitumor efficacy while improving quality of life. This review highlights the importance of a personalized, multidisciplinary approach, integrating therapeutic innovations with individualized supportive care, in a context marked by emerging differentiations of therapeutic options for mCSPC.

Introduction: Advance directives (AD) are rarely used although they have been enshrined in law since 2005. Health establishments have a duty to inform patients regarding AD. However, studies have shown little awareness of this law in the healthcare environment. Our study analyzes the perception of AD by oncohematology caregivers.

Methods: This is an observational, descriptive and prospective study conducted with a 12-item questionnaire distributed to oncohematology nurses and nursing assistants. Statistical analyses were carried out using a significance threshold of 0.05 and using the Chi², Fisher or Kruskal-Wallis tests.

Results: The questionnaire was completed by 138 caregivers. Among them, 63.8% felt they had "very weak" or "weak" knowledge of ADs. The level of training was considered insufficient by 83.8% of respondents. Those with a good level of knowledge of ADs approached them more often (P=0.003) and felt more comfortable doing so (P<0.001). More than 90% of caregivers were "convinced" or "very convinced" by ADs but less than half understood their impact in clinical practice.

Discussion: ADs remain little known among caregivers who do not feel comfortable approaching them. Training in ADs is an improvement clue because it allows you to approach them more often and to feel more comfortable. ADs are well-received by caregivers but their impact is little perceived in practice. The involvement of caregivers in end-of-life decisions through multidisciplinarity should be strengthened in oncohematology based on the palliative care model.

Ewing sarcoma (ES) is an aggressive sarcoma with a peak incidence in adolescents and young adults. Current therapy involves multiagent chemotherapy and local therapy but despite intensification of treatment patients with metastases at diagnosis and recurrent disease have poor prognosis. Improved understanding of ES biology has identified novel targets with promising activity in ES patients. Tyrosine kinase inhibitors are currently being evaluated as combination and maintenance therapy. Other emerging therapies include those that target the EWSR1:FLI1 fusion oncoprotein, cell cycle, apoptotic and DNA-repair pathways. Immunotherapeutic approaches are also being investigated, particularly CAR-T and CAR-NK cell therapy. Close collaboration between clinicians and biologists has also highlighted the importance of biomarkers that are still being validated prospectively and might be incorporated into standard of care in the future.

Introduction: Sickle cell disease affects approximately 30,000 people in France. Between 1988 and 2022, 700 patients underwent allogeneic hematopoietic stem cell transplantation (HSCT), mainly children, but the procedure is increasingly offered to adults. The medical and psychological complexities of transplantation in this population require specific attention to optimize care.

Methods: Our work was based on a literature review and team experience, following the standard methodology of the SFGM-TC. Our focus was on pre-transplant evaluation, transfusion preparation, fertility preservation, post-transplant medical follow-up, psychological support, and pain management.

Results: Transplantation for sickle cell disease requires comprehensive assessment of organ damage, transfusion preparation, and close interdisciplinary collaboration. Fertility is a major concern, with tailored protocols based on the patient's sex and age. Post-transplant pain, often complex, necessitates multidisciplinary follow-up and team awareness. Psychologically, the post-transplant transition is marked by a loss of bearings, requiring personalized psychological support.

Conclusion: Interdisciplinary collaboration, meticulous preparation, and long-term follow-up are essential to improving transplant outcomes in sickle cell patients. Enhanced team awareness and the involvement of expert patients are also recommended.