Journal of the National Cancer Center最新文献

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a groundbreaking approach in cancer treatment, utilizing the immune system's capabilities to combat malignancies. This innovative therapy involves extracting T-cells from a patient's blood, genetically modifying them to target specific cancer cells, and reinfusing them back into the patient's body. The genetically modified T-cells then seek out and eliminate cancer cells, offering a promising therapeutic strategy. Since its initial approval in 2017, CAR-T therapy has witnessed remarkable advancements and updates. Notably, CAR-T therapy, which was initially developed for hematological malignancies, has expanded its scope to target solid tumors. Currently, clinical trials are underway to explore the efficacy of CAR-T therapy in treating various solid tumors, such as lung cancer, breast cancer, and ovarian cancer. These trials hold great potential to revolutionize cancer treatment and provide new hope to patients with challenging-to-treat solid tumors. In this mini-review, we present an overview of CAR-T therapy's mechanisms, emphasizing its role in targeting cancer cells and the potential therapeutic benefits. Additionally, we discuss the recent progress and updates in CAR-T therapy, particularly its application in treating solid tumors, and highlight the ongoing clinical trials aimed at broadening its therapeutic horizon. The evolving landscape of CAR-T therapy signifies a promising direction in cancer therapeutics, with the potential to revolutionize the treatment of both hematological and solid tumor malignancies.

Lung cancer is the leading cause of cancer-related deaths worldwide. Bone is a common metastatic site of lung cancer, about 50% of bone metastatic patients will experience skeletal related events (SREs). SREs not only seriously impact the quality of life of patients, but also shorten their survival time. The treatment of bone metastasis requires multi-disciplinary therapy (MDT) and development of individualized treatment plan. In order to standardize the diagnosis and treatment of bone metastasis in lung cancer, the expert group of the MDT Committee of the Chinese Medical Doctor Association has developed the expert consensus on the diagnosis and treatment of lung cancer bone metastasis.

Pancreatic ductal adenocarcinoma (PDAC) stands as a profoundly heterogeneous and aggressive malignancy, manifesting a discouragingly limited response to conventional therapeutic interventions. Within the intricate tapestry of the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) emerge as pivotal constituents, wielding the capacity to propel the malignant attributes of neoplastic cells while bolstering their deftness in thwarting treatments. The rapid evolution of nanomedicinal technologies ushers in fresh avenues for therapeutic paradigms meticulously honed to target CAFs. Notably, a recent proposition by Yuan et al. introduces a PDAC treatment strategy metaphorically akin to “shooting fish in a barrel.” By adeptly capitalizing on the spatial distribution of the CAF barricade encircling the tumor, this innovative approach orchestrates a metamorphosis of CAFs, transitioning them from impediments to drug delivery into reservoirs of therapeutic agents. The resultant outcome, an augmentation of chemotherapy and immunotherapy efficacy, attests to the transformative potential of this concept. The study not only bequeaths novel insights and methodologies to surmount barriers in drug delivery for tumor treatment but also holds promise in elevating the precision, efficacy, and safety of tailored therapeutic regimens. Within this discourse, we meticulously evaluate Yuan et al.'s research, scrutinizing its merits and limitations, and cast a forward-looking gaze upon the formulation, validation of efficacy, and clinical translation of nanomedicines targeting CAFs.

Treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2; HER2-low) has drawn much attention in recent years. With the proven therapeutic effect of trastuzumab deruxtecan (T-DXd) in patients with HER2-low (immunohistochemistry [IHC] 1+, or IHC2+/in situ hybridization [ISH]-) breast cancer, HER2-low may become a new subtype of targeted therapy for breast cancer. The expert committee formulated this consensus based on the current clinical studies and clinical medication experience. The current consensus is the collaborative work of an interdisciplinary working group, including experts in the fields of pathology and oncology. The purpose of this consensus was to guide the clinical diagnosis and treatment of HER2-low breast cancer, thereby prolonging the overall survival of patients.

Cellular senescence is characterized by a generally irreversible cell cycle arrest and the secretion of bioactive factors known as the senescence-associated secretory phenotype (SASP). In an oncogenic context, senescence is considered a tumor suppressive mechanism as it prevents cell proliferation and inhibits the progression from pre-malignant to malignant disease. However, recent studies have demonstrated that senescent tumor cells, which could spontaneously exist within cancer tissues or arise in response to various cancer interventions (the so-called therapy-induced senescence, TIS), can acquire pro-tumorigenic properties and are capable of driving local and metastatic relapse. This highlights the complex and multifaceted nature of cellular senescence in cancer biology. Here, we summarize the current knowledge of the pathological function of therapy-induced senescent tumor cells and discuss possible mechanisms by which tumor cell senescence contributes to cancer relapse. We also discuss implications for future studies toward targeting these less appreciated cells.

Background

Although poor oral health and several lifestyle factors have been found to be associated with cancer risk, their joint relationship has rarely been studied.

Methods

We prospectively examined the associations of oral health and healthy lifestyle factors with cancer risk among 0.5 million rural and urban residents from the China Kadoorie Biobank (2004–2015). Oral health status was assessed from self-reported baseline questionnaires. A healthy lifestyle index comprising non-smoking, non-drinking, ideal body shape, physical activity and healthy diet was calculated for each participant, and categorized into favorable, intermediate and unfavorable lifestyle behavior. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) relating oral health and healthy lifestyle index to cancer risk using Cox proportional hazards models. We estimated the population attributable risk percent (PAR%) and 95% CIs using multivariate models.

Results

During a median follow-up of 9 years, 23,805 new cancer cases were documented, with 52% from rural areas and 48% from urban areas. Compared with those with good oral health and favorable lifestyle, participants with poor oral health and unfavorable lifestyle had a higher risk of developing cancer in both rural (adjusted HR, 1.55 [95% CI, 1.39–1.74]; P for trend < 0.001) and urban areas (adjusted HR, 1.44 [95% CI, 1.24–1.67]; P for trend < 0.001). A significant multiplicative interaction between oral health and healthy lifestyle index on cancer risk was found in rural residents (P for interaction = 0.004) rather than in urban residents (P for interaction = 0.973). Assuming poor oral health as an additional risk factor, the PAR% of total cancer increased by 3.0% and 1.1% for participants with intermediate lifestyle and unfavorable lifestyle, respectively.

Conclusions

These findings suggest a joint effect of oral health and common lifestyle factors on cancer risk. Promotion of healthy lifestyle by integration of good oral health would be beneficial to consider in cancer prevention strategies.

Objective

Accurate prognostic predictions and personalized decision-making on induction chemotherapy (IC) for individuals with locally advanced nasopharyngeal carcinoma (LA-NPC) remain challenging. This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival (OS) and their value in guiding treatment in patients with LA-NPC.

Methods

Individuals with LA-NPC were reviewed retrospectively. Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods, the interpretable eXtreme Gradient Boosting (XGBoost) risk prediction model, and DeepHit time-to-event neural network. The models' prediction performances were compared using the concordance index (C-index) and the area under the curve (AUC). The patients were divided into two cohorts based on the risk predictions of the most successful model. The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone.

Results

The 1 221 eligible individuals, assigned to the training (n = 813) or validation (n = 408) set, showed significant respective differences in the C-indices of the XGBoost, DeepHit, and nomogram models (0.849 and 0.768, 0.811 and 0.767, 0.730 and 0.705). The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS (0.881 and 0.760, 0.845 and 0.776, and 0.764 and 0.729, P < 0.001). IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group.

Conclusion

This research used machine-learning algorithms to create and verify a comprehensive model integrating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC. This model could be valuable for delivering patient counseling and conducting clinical evaluations.