Strategy For Treatment Of Tumors Research Articles

Evolution of treatment strategies for solid tumors with RET rearrangement in China and real-world treatment status of Non-small Cell Lung Cancer (NSCLC)

ObjectiveThe present study endeavors to furnish an exhaustive review of the research advancements on solid tumors harboring RET rearrangement within the Chinese context, particularly emphasizing the examination of real-world therapeutic strategies and clinical outcomes observed in individuals diagnosed with advanced non-small cell lung cancer (NSCLC). The review delves into a critical assessment of the therapeutic efficacy of targeted RET inhibitors, while also scrutinizing the diverse array of treatment modalities employed in the Chinese patient population.MethodsThe study conducted a comprehensive review of the advancements made by Chinese scholars in the realm of RET driver genes. It delved into the analysis of the incidence of RET rearrangements in solid tumors, alongside an examination of the varied treatment paradigms and their current status within China. Utilizing the RECIST 1.1 criteria, the study evaluated the therapeutic efficacy achieved in RET-positive NSCLC patients undergoing diverse treatment modalities. Furthermore, treatment-related adverse events (TRAEs) were meticulously graded following the Common Terminology Criteria for Adverse Events (CTCAE).ResultsA retrospective, multi-center, real-world analysis was conducted, encompassing 64 patients diagnosed with pathologically confirmed RET rearrangement advanced non-small cell lung cancer (NSCLC) between December 2015 and November 2023. Notably, KIF5B-RET emerged as the most prevalent RET fusion partner, accounting for 59.4% of cases. Therapeutic interventions among these patients included specific targeted inhibitors such as Pralsetinib (48.4%), chemotherapy (34.3%), multi-target inhibitors (15.6%), and one case (1.6%) involving immunotherapy combined with anti-angiogenic therapy. In terms of progression-free survival (PFS), Pralsetinib monotherapy demonstrated a median PFS of 16.03 months, outperforming chemotherapy (2.87 months; p < 0.0001), chemotherapy combined with anti-angiogenic therapy (6.90 months; p = 0.048), and multi-target inhibitors (2.50 months; p < 0.0001). Furthermore, the one-year and two-year overall survival (OS) rates for Pralsetinib monotherapy were 64.3% and 46.4%, respectively. Regarding safety, 71.0% of patients receiving Pralsetinib experienced at least one adverse event, with 45.2% classified as grade 3–4 in severity. Notably, no fatalities were attributed to adverse events. Common adverse events included hemoglobin reduction (35.5%) and neutropenia (32.3%), indicative of an overall favorable safety profile for Pralsetinib in this patient population.ConclusionThis study encapsulates the research endeavors and treatment advancements of RET rearrangement solid tumors within the Chinese healthcare landscape, specifically highlighting the diverse real-world therapeutic approaches and their effectiveness in managing advanced RET rearrangement NSCLC among Chinese patients. Notably, targeted RET inhibitors like Pralsetinib have emerged as potent therapeutic agents, exhibiting remarkable efficacy and a manageable safety profile in this patient cohort. These findings underscore the potential of Pralsetinib and similar targeted therapies as novel treatment options for individuals with RET fusion-positive NSCLC.

Natural diterpene carrier-free hydrogel enhances antigen presentation and intensifies T cell activation for tumor immunotherapy

Although immunotherapy has revolutionized cancer treatment, the low immunogenicity, insufficient T cells intratumoral infiltration and defective antigen presentation in the “cold” tumor microenvironment limit its clinical application. To address this challenge, enlightened by the clinical combined application of antitumor herb medicines, we developed a carrier-free hydrogel KEEM by integrating multiple natural active lipophilic components with manganese ions into a natural co-assembled ternary system. The KEEM hydrogel induced the formation of hydroxyl radicals by Fenton-like reactions, leading to apoptosis, while simultaneously inducing tumor cell ferroptosis through the system xc−-GSH-GPX4 axis. Subsequent release of damage-associated molecular patterns (DAMPs) proved the emergence of immunogenic cell death (ICD). Additionally, manganese ions could directly activate the cGAS-STING pathway, further amplifying the immunostimulatory effects. This synergistic effect promoted dendritic cell maturation thus enhancing antigen presentation, and mediating the change of tumor microenvironment (TME) from “cold” to “hot”. In hepatoma ascites and melanoma models, KEEM combined with immune checkpoint blockade and adoptive T cell therapy respectively demonstrated promising anti-tumor effects in vivo, meanwhile showing excellent biocompatibility and biosafety. Thus, the combination of this multi-diterpenoids carrier-free hydrogel with immunotherapy offers a new strategy for clinical immune-refractory tumor treatment.

Compact Molecular Conformation of Prodrugs Enhances Photocleaving Performance for Tumor Vascular Growth Inhibition.

Highly spatiotemporal-resolved photomodulation demonstrates promise for investigating key biological events in vivo and in vitro, such as cell signaling pathways, neuromodulation, and tumor treatment without side effects. However, enhancing the performance of photomodulation tools remains challenging due to the limitations of the physicochemical properties of the photoactive molecules. Here, a compact, stable intramolecular π-πstacking conformation forming between the target molecule (naproxen) and the perylene-based photoremovable protecting group is discovered to confine the motion of the photolabile bond and then enhance the photocleavage quantum yield. In conjunction with a red-absorbing photosensitizer, the photocleavage wavelength is extended to the red region via triplet-triplet annihilation. In particular, the triplet lifetime of the prodrug can be extended via the linked steric hindrance to improve the conversion yield via TTA. Using the new photomodulation tool, it is precisely photoreleased cyclooxygenase-2 inhibitors for tumor vascular growth suppression in vivo. In combination with cisplatin, over 90% efficient inhibition of malignant breast tumors is observed via the synergistic tumor treatment strategy. These findings provide a new concept for the rational design of efficient photocleavage and have implications for photomodulating cell signaling pathways in tumor therapy, as well as laying a solid foundation for the development of phototherapeutic approaches.

Decoding tumor-fibrosis interplay: mechanisms, impact on progression, and innovative therapeutic strategies

Malignant tumors are a category of diseases that possess invasive and metastatic capabilities, with global incidence and mortality rates remaining high. In recent years, the pivotal role of fibrosis in tumor progression, drug resistance, and immune evasion has increasingly been acknowledged. Fibrosis enhances the proliferation, migration, and invasion of tumor cells by modifying the composition and structure of the extracellular matrix, thereby offering protection for immune evasion by tumor cells. The activation of cancer-associated fibroblasts (CAFs) plays a significant role in this process, as they further exacerbate the malignant traits of tumors by secreting a variety of cytokines and growth factors. Anti-fibrotic tumor treatment strategies, including the use of anti-fibrotic drugs and inhibition of fibrosis-related signaling pathways such as Transforming Growth Factor-β (TGF-β), have demonstrated potential in delaying tumor progression and improving the effectiveness of chemotherapy, targeted therapy, and immunotherapy. In the future, by developing novel drugs that target the fibrotic microenvironment, new therapeutic options may be available for patients with various refractory tumors.

T1/T2 Proportional Magnetic Resonance Nanoprobe Monitoring Tumor Autophagy during Chemotherapy.

Autophagy leads to cellular tolerance of the therapeutic pressure of chemotherapeutic drugs, resulting in treatment resistance. Therefore, the effective monitoring of the autophagy status of tumors in vivo and the regulating of the autophagy level are crucial for improving the efficacy of chemotherapy. In this work, we grafted nitroxide radicals onto the surface of iron oxide nanoparticles (Fe3O4 NPs) using dendrimer polymers, yielding Fe3O4-NO· NPs that are responsive to reactive oxygen species (ROS) and possess enhanced T1 and T2 signal capabilities in a magnetic resonance imaging (MRI) measurement. The ROS in tumor cells generated by autophagy quenches the nitroxide radicals, thereby weakening the T1 signal. In contrast, Fe3O4 NPs are unaffected by intracellular ROS, leading to a stable T2 signal. By comparing the intensity ratio of T1 to T2 in Fe3O4-NO· NPs, we can evaluate the in vivo autophagy status within tumors in real time. It also revealed that Fe3O4-NO· NPs loaded with doxorubicin (Dox) and combining the autophagy inhibitor exhibited high antitumor activity in cells and tumor-bearing mice. This system, which combines real-time monitoring of tumor cell autophagy with the delivery of chemotherapeutic drugs, provides an innovative and effective strategy for tumor treatment with potential clinical application prospects.

Injectable hydrogels for Fenton-like Mn2+/Fe2+ delivery with enhanced chemodynamic therapy prevent osteosarcoma recurrence and promote wound healing after excision surgery

Local recurrence of osteosarcoma and wound healing after excision surgery are major challenges in clinical research. The present anti-tumor treatments could inhibit normal tissues, resulting in difficulties in surgical wound healing. In this study, we constructed an injectable hydrogel as a platform to co-deliver MnO2 nanoparticles and ferrocene Fc, termed as (MnO2/Fc)@PLGA for osteosarcoma treatment and wound healing after excision. By simple local injection, the hydrogel could form a protective barrier on the surgical wound after osteosarcoma excision, which could promote wound healing and steady release of MnO2/Fc nanoparticles. The released MnO2/Fc might undergo the Fenton reaction through Mn2+/Fe2+ to inhibit osteosarcoma cells with chemodynamic therapy (CDT). Furthermore, MnO2 could catalyze endogenous H2O2 to produce O2, which eliminates the adverse effects of H2O2 and remodels the hypoxic state in the local lesions. The increased O2 facilitated surgical wound healing and anti-tumor effects by regulating the hypoxia inducible factor-1 functions. In conclusion, (MnO2/Fc)@PLGA hydrogel could effectively prevent local recurrence of osteosarcoma and promote wound healing after excision surgery, thereby providing a novel strategy for tumor treatment and tissue repair.

Multifaceted modeling of small intestinal neuroendocrine tumors

Small intestinal neuroendocrine tumors, siNETs, are a group of rare cancers that arise from neuroendocrine cells in the lining of the jejunum and ileum, which are either classified as tumors, siNETs, or carcinomas, siNECs. Current treatment strategies for low grade tumors include surgical resection, peptide radionucleotide receptor therapy, and somatostatin analogues, while high grade and recurrent tumors may receive cytotoxic chemotherapy. These limited treatment options are linked to the lack of representative models that can both reflect the biology of the tumor and are amenable to mid-to-high throughput experimentation. Cell line generation is challenging considering the indolent nature of primary lesions, although some attempts have been successful using a variety of methods and include the primary P-STS line and those derived from metastatic lesions including GOT1, CNDT2.5 and HC45. Patient-derived modeling, including organoids and xenografting, have allowed for multicellular and three-dimensional representations of the original tumor. These specific models allow for multicellular populations derived from the tumor, providing better tumor representation for use in drug screening and in vitro assays. Currently, there are limited, although increasing, published models of siNETs implanted as xenografts in mice and zebrafish. As these cellular and animal models provide insights on siNET biology, theragnostic modeling has provided key information on the clinical progression and treatment of this disease. Significant strides toward more representative models have been made throughout the last decade. In this review, details of these attempts as well as future directions and strategies for more robust models will be addressed.

Priming of cancer-immunity cycle by alleviating hypoxia-induced ferroptosis resistance and immunosuppression

Stimulating a robust cancer-immunity cycle (CIC) holds promising potential for eliciting potent and enduring immune responses for cancer immunotherapy. However, designing a therapeutic nanomaterial capable of both enhancing tumor immunogenicity and mitigating immunosuppression is challenging and often associated with complicated design paradigms and immune-related adverse effects. Herein, a multienzyme-mimetic alloy nanosheet incorporating palladium (Pd) and iron (Fe) is developed, which can prime effective CIC by overcoming ferroptosis resistance for enhancing tumor immunogenicity and reprograming the tumor microenvironment for enhanced second near-infrared (NIR-II) photoimmunotherapy. The nanosheets accumulate in tumors when administered intravenously and counteract hypoxia through catalase-like oxygen production and subsequent reduction of hypoxia-inducible factor-1α, M2-like macrophages, regulatory T-cell, and programmed death-ligand 1 (PD-L1) expression. The surface plasmon resonance of the nanosheets enables NIR-II phototherapy and photoacoustic imaging, coupling with its ferroptosis and tumor microenvironment reprogram properties to synergize with anti-PD-L1 checkpoint blockade therapy to achieve satisfactory antitumor outcome. This study offers a strategy for localized tumor treatment and boosting the CIC through a straightforward and inexpensive nanomaterial design.

NRG1 Fusions in NSCLC: Being eNRGy Conscious.

Fusions in neuregulin 1 (NRG1) are rare oncogenic drivers that occur across a number of tumor types, including non-small cell lung cancer (NSCLC). NRG1 has an EGF-like domain that serves as a ligand for HER3 receptors, inducing heterodimerization, usually with HER2, and subsequent activation of oncogenic downstream signaling pathways. Emerging evidence suggests that NSCLC harboring NRG1 fusions do not respond as well to standard therapeutic options including chemotherapy and immunotherapy, and prognosis is poor. Novel treatment approaches targeting the HER2/HER3 pathway are under investigation. Here, we discuss the biology and detection of NRG1 fusions in NSCLC and promising targeted treatment strategies for tumors harboring the mutation.

A glutathione-activated bismuth-gallic acid metal-organic framework nano-prodrug for enhanced sonodynamic therapy of breast tumor

Sonodynamic therapy is a promising, noninvasive, and precise tumor treatment that leverages sonosensitizers to generate cytotoxic reactive oxygen species during ultrasound stimulation. Gallic acid (GA), a natural polyphenol, possesses certain anti-tumor properties, but exhibits significant toxicity toward normal cells, limiting its application in cancer treatment. To overcome this issue, we synthesized a bismuth-gallic acid (BGA), coordinated metal–organic framework (MOF) nano-prodrug. Upon encountering glutathione (GSH), BGA gradually dissociated and depleted GSH, releasing GA, which had anti-tumor effects. As an MOF with semiconductor properties, BGA primarily produced superoxide anion radical upon ultrasound excitation. After the release of GA, GA generated superoxide anion radical and further produced high toxic singlet oxygen under ultrasound stimulation, while further oxidizing and consuming GSH, enhancing sonocatalytic performance. Additionally, the released GA induced cell cycle arrest, ultimately leading to apoptosis. Our results revealed that BGA, as a GSH-activated, metal-polyphenol MOF nano-prodrug, showed potential for use in breast tumor sonodynamic therapy, providing a novel strategy for precise tumor treatment.

Machine learning-based individualized survival prediction model for prognosis in osteosarcoma: Data from the SEER database.

Patient outcomes of osteosarcoma vary because of tumor heterogeneity and treatment strategies. This study aimed to compare the performance of multiple machine learning (ML) models with the traditional Cox proportional hazards (CoxPH) model in predicting prognosis and explored the potential of ML models in clinical decision-making. From 2000 to 2018, 1243 patients with osteosarcoma were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Three ML methods were chosen for model development (DeepSurv, neural multi-task logistic regression [NMTLR]) and random survival forest [RSF]) and compared them with the traditional CoxPH model and TNM staging systems. 871 samples were used for model training, and the rest were used for model validation. The models' overall performance and predictive accuracy for 3- and 5-year survival were assessed by several metrics, including the concordance index (C-index), the Integrated Brier Score (IBS), receiver operating characteristic curves (ROC), area under the ROC curves (AUC), calibration curves, and decision curve analysis. The efficacy of personalized recommendations by ML models was evaluated by the survival curves. The performance was highest in the DeepSurv model (C-index, 0.77; IBS, 0.14; 3-year AUC, 0.80; 5-year AUC, 0.78) compared with other methods (C-index, 0.73-0.74; IBS, 0.16-0.17; 3-year AUC, 0.73-0.78; 5-year AUC, 0.72-0.78). There are also significant differences in survival outcomes between patients who align with the treatment option recommended by the DeepSurv model and those who do not (hazard ratio, 1.88; P < .05). The DeepSurv model is available in an approachable web app format at https://survivalofosteosarcoma.streamlit.app/. We developed ML models capable of accurately predicting the survival of osteosarcoma, which can provide useful information for decision-making regarding the appropriate treatment.

Tumor Microenvironment-Responsive Biodegradable Nanomedicine for Self-Enhanced Synergistic Chemo-, Photothermal, and Chemodynamic Therapy.

The nanoscale multidrug codelivery system for synergistic therapy is an effective strategy for tumor treatment. However, the low drug delivery efficiency and poor therapeutic effects limit its application. Here, based on the coordination effect of Artemisinin (Art), quercetin (Qc), and Fe3+, we had constructed a safe and efficient carrier-free hyaluronic acid (HA)-modified Art-Fe-Qc nanoparticles (AFQ@HA NPs) for enhanced chemotherapy/photothermal therapy (PTT)-chemodynamic therapy (CDT) synergistic therapy, which achieved an ultrahigh drug loading efficiency and a multifunction anticancer strategy. The results showed that high drug loading was achieved based on drug coordination self-assembly, with Art and Qc contents of 38.6 and 42.7%, respectively. At the same time, based on the Qc-Fe coordination molecular network, the system had excellent photothermal conversion performance with an efficiency of 57.3% and could effectively inhibit the expression of HSP70, achieving enhanced PTT. Further, under the stimulation of excessive H2O2 and glutathione (GSH) in the tumor microenvironment, the AFQ@HA NPs were continuously degraded, while releasing Art and Fe3+/Fe2+ to achieve iron ion-enhanced CDT. The results of in vitro and in vivo experiments showed that AFQ@HA NPs could achieve chemotherapy-PTT-CDT synergistic therapy in response to tumor microenvironment by passively targeting and actively targeting tumor cells with CD44, demonstrating its excellent targeted antitumor effects.

Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.

Cell death is of great significance in maintaining tissue homeostasis and bodily functions. With considerable research coming to the fore, it has been found that programmed cell death presents in multiple modalities in the body, which is not only limited to apoptosis, but also can be divided into autophagy, pyroptosis, ferroptosis, mitotic catastrophe, entosis, netosis, and other ways. Different forms of programmed cell death have disparate or analogous characteristics with each other, and their occurrence is accompanied by multiple signal transduction and the role of a myriad of regulatory factors. In recent years, scholars across the world have carried out considerable in-depth research on programmed cell death, and new forms of cell death are being discovered continually. Concomitantly, the mechanisms of intricate signaling pathways and regulators have been discovered. More critically, cancer cells tend to choose distinct ways to evade cell death, and different tumors adapt to different manners of death. Therefore, targeting the cell death network has been regarded as an effective tumor treatment strategy for a long time. The objective of our paper is to review the signaling pathways and gene regulation in several typical types of programmed cell death and their correlation with cancer.

Photoferroptosis as a potent strategy for neuroblastoma treatment

Photodynamic therapy (PDT) and photothermal therapy (PTT) have been developed to treat tumors with potential of clinical applications due to their high spatiotemporal selectivity and non-invasiveness. Nevertheless, the hypoxia within the tumor microenvironment (TME) limits the efficacy of PDT. PTT has the risk of damaging surrounding normal tissues due to the high temperatures essential for killing tumor cells. Herein, we propose a new tumor treatment strategy based on photo-triggered ferroptosis of tumor cells, which is termed photoferroptosis therapy (PFT). The PFT agent (CuS&AIPH@PEG-PAE@PM) was synthesized by encapsulating a radical generator (2,2’-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH) and a photothermal agent (copper sulfide, CuS) into an amphiphilic polymer (poly(ethylene glycol)-poly(β-amino ester), PEG-PAE) via self-assembly and a following coating with platelet membrane (PM). Under near-infrared (NIR) irradiation, the PFT agent CuS&AIPH@PEG-PAE@PM generates abundant alkyl radicals (R●) to trigger tumor cell ferroptosis in a moderate temperature and oxygen-independent manner. Meanwhile, the PFT agent also reduces the GSH level and thus suppresses GPX4 expression to promote ferroptosis, which further consolidates the antitumor effect of PFT. The PFT is expected to establish a promising phototherapy strategy against tumors, which has the potential to overcome the limitations of PDT and PTT.

Hepatoma-Targeting and ROS-Responsive Polymeric Micelle-Based Chemotherapy Combined with Photodynamic Therapy for Hepatoma Treatment.

The combination of nanoplatform-based chemotherapy and photodynamic therapy (PDT) is a promising way to treat cancer. Celastrol (Cela) exhibits highly effective anti-hepatoma activity with low water solubility, poor bioavailability, non-tumor targeting, and toxic side effects. The combination of Cela-based chemotherapy and PDT via hepatoma-targeting and reactive oxygen species (ROS)-responsive polymeric micelles (PMs) could solve the application problem of Cela and further enhance antitumor efficacy. In this study, Cela and photosensitizer chlorin e6 (Ce6) co-loaded glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) PMs (Cela/Ce6/GCTR PMs) were prepared and characterized. The safety, ROS-sensitive drug release, and intracellular ROS production were evaluated. Furthermore, the in vitro anti-hepatoma effect and cellular uptaken in HepG2 and BEL-7402 cells, and in vivo pharmacokinetic, tissue distribution, and antitumor efficacy of Cela/Ce6/GCTR PMs in H22 tumor-bearing mice were then investigated. Cela/Ce6/GCTR PMs were successfully prepared with nanometer-scale particle size, favorable drug loading capacity, and encapsulation efficiency. Cela/Ce6/GCTR PMs exhibited a strong safety profile and better hemocompatibility, exhibiting less damage to normal tissues. Compared with Cela-loaded GCTR PMs, the ROS-responsiveness of Cela/Ce6/GCTR PMs was increased, and the release of Cela was accelerated after combination with PDT. Cela/Ce6/GCTR PMs can efficiently target liver tumor cells by uptake and have a high cell-killing effect in response to ROS. The combination of GCTR PM-based chemotherapy and PDT resulted in increased bioavailability of Cela and Ce6, improved liver tumor targeting, and better anti-hepatoma effects in vivo. Hepatoma-targeting and ROS-responsive GCTR PMs co-loaded with Cela and Ce6 combined with PDT exhibited improved primary hepatic carcinoma therapeutic effects with lower toxicity to normal tissues, overcoming the limitations of monotherapy and providing new strategies for tumor treatment.

Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) combined with conventional MRI for the detection of skull-base invasion in nasopharyngeal carcinoma: comparison with 18F-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT).

The extent of skull base invasion (SBI) in nasopharyngeal carcinoma (NPC) directly impacts tumor staging, treatment strategies, and prognosis assessment for NPC patients, emphasizing the critical need for prompt diagnosis and precise assessment of invasion. Thus, we aimed to integrate the advantages of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and conventional magnetic resonance imaging (cMRI), and assess their combined diagnostic efficacy versus that of 18F-sodium fluoride (18F-NaF) positron emission tomography/computed tomography (PET/CT) for detecting SBI in NPC patients. The study prospectively and randomly recruited 62 patients newly diagnosed with NPC by pathological biopsy at the Cancer Center of Affiliated Hospital of Guangdong Medical University from January 2021 to September 2022. All patients underwent baseline cMRI, IVIM-DWI, and PET/CT scans. The IVIM-DWI analysis included 3 primary parameters: true diffusion coefficient (D), pseudodiffusion coefficient (D*), and pseudodiffusion fraction (f). SBI was defined as the involvement of any substructure confirmed by follow-up MRI and clinical symptoms. Inter-observer agreement was evaluated utilizing the intraclass correlation coefficients (ICC) and kappa coefficients. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of cMRI, IVIM-DWI plus cMRI, and PET/CT. DeLong test was used to compare the areas under the curve (AUC) of the 3 modalities. Excellent inter-observer reliability was observed (range, 0.841-0.946). Among the IVIM-DWI parameters, D* + f demonstrated comparable accuracy to D + D* + f (AUC 0.906 vs. 0.904; sensitivity 88.9% vs. 89.8%; specificity 92.3% vs. 91.0%). IVIM-DWI plus cMRI yielded an overall AUC of 0.947, sensitivity of 92.6%, and specificity of 96.8%, surpassing cMRI alone with an AUC of 0.914 (P=0.025), sensitivity of 91.2%, and specificity of 91.7%, as well as 18F-NaF PET/CT with an AUC of 0.852 (P<0.001), sensitivity of 80.1%, and specificity of 90.4%. In detecting substructures of SBI, IVIM-DWI plus cMRI showed superior performance compared to 18F-NaF PET/CT within the petrous part of the temporal bone (AUC 0.968 vs. 0.871, P=0.011; sensitivity 93.5% vs. 87.1%, specificity 100% vs. 87.1%), pterygopalatine fossa (AUC 0.935 vs. 0.831, P=0.032; sensitivity 93.9% vs. 69.7%, specificity 93.1% vs. 96.6%), and foramen ovale (AUC 0.885 vs. 0.710, P=0.019; sensitivity 76.9% vs. 61.5%, specificity 100% vs. 80.6%). IVIM-DWI plus cMRI can accurately detect SBI and the substructures in NPC, providing a valuable reference for personalized treatment strategies and precise prognosis assessment.

Regulation of Tumor Microenvironment through YAP/TAZ under Tumor Hypoxia.

In solid tumors such as hepatocellular carcinoma (HCC), hypoxia is one of the important mechanisms of cancer development that closely influences cancer development, survival, and metastasis. The development of treatments for cancer was temporarily revolutionized by immunotherapy but continues to be constrained by limited response rates and the resistance and high costs required for the development of new and innovative strategies. In particular, solid tumors, including HCC, a multi-vascular tumor type, are sensitive to hypoxia and generate many blood vessels for metastasis and development, making it difficult to treat HCC, not only with immunotherapy but also with drugs targeting blood vessels. Therefore, in order to develop a treatment strategy for hypoxic tumors, various mechanisms must be explored and analyzed to treat these impregnable solid tumors. To date, tumor growth mechanisms linked to hypoxia are known to be complex and coexist with various signal pathways, but recently, mechanisms related to the Hippo signal pathway are emerging. Interestingly, Hippo YAP/TAZ, which appear during early tumor and normal tumor growth, and YAP/TAZ, which appear during hypoxia, help tumor growth and proliferation in different directions. Peculiarly, YAP/TAZ, which have different phosphorylation directions in the hypoxic environment of tumors, are involved in cancer proliferation and metastasis in various carcinomas, including HCC. Analyzing the mechanisms that regulate the function and expression of YAP in addition to HIF in the complex hypoxic environment of tumors may lead to a variety of anti-cancer strategies and combining HIF and YAP/TAZ may develop the potential to change the landscape of cancer treatment.

The Pattern of Copper Release in Copper‐Based Nanoparticles Regulates Tumor Proliferation and Invasiveness in 3D Culture Models

Cancer is a leading cause of death worldwide. Glioblastoma (GBM) is a major challenge in oncology due to its highly invasive nature and limited treatment options. GBM's aggressive migration beyond tumor margins and rapid tumor growth hinders success in patient treatment. Localized therapeutic delivery, such as the use of transition metals like copper, is highlighted as a novel therapeutic agent for many potential biomedical applications. Herein, it is aimed to study the effects of Cu release on the proliferation and invasiveness of cancer cells. To this end, novel copper‐based nanostructures with different release patterns are designed. Using a complex 3D cell culture model to mimic the tumor microenvironment, it is shown that different patterns of copper ion release have a strong impact on GBM progression and invasiveness. The findings highlight the importance of optimizing localized copper release patterns to tailor different tumor treatment strategies. They also show the potential and suitability of 3D microchips as instruments to study the behavior of tumor spheroids. In spite of their limitations, these 3D microdevices enable a controlled and close monitoring of the influence of environmental factors (such as the presence of Cu ions) on the proliferation and invasiveness of the cells, with a better approach to reality compared to 2D models and with a more controlled environment, compared to an in vivo model.

Surgical management of rare tumors (Part 1).

With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers and the Children's Oncology Group fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g., pleuropulmonary blastoma and desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g., thyroid, melanoma, and gastrointestinal stromal tumor). Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14. This article highlights several of the most common rare tumor types.

Primary treatments for solitary hepatocellular carcinoma ≤ 3 cm: A systematic review and network meta-analysis.

Various treatment modalities are available for small solitary hepatocellular carcinoma (HCC), yet the optimal primary treatment strategy for tumors ≤ 3 cm remains unclear. This network meta-analysis investigates the comparative efficacy of various interventions on the long-term outcomes of patients with solitary HCC ≤ 3 cm. A systematic search of electronic databases from January 2000 to December 2023 was conducted to identify studies that compared at least two of the following treatments: surgical resection (SR), radiofrequency ablation (RFA), microwave ablation (MWA), and transarterial chemoembolization (TACE). Survival data were extracted, and pooled hazard ratios with 95% confidence intervals were calculated using a frequentist network meta-analysis. A total of 30 studies, comprising 2 randomized controlled trials and 28 retrospective studies, involving 8,053 patients were analyzed. Surgical resection showed the highest overall survival benefit with a p-score of 0.95, followed by RFA at 0.59, MWA at 0.23, and TACE, also at 0.23. Moreover, SR provided the most significant recurrence-free survival advantage, with a p-score of 0.95, followed by RFA at 0.31 and MWA at 0.19. Sensitivity analyses, excluding low-quality or retrospective non-matched studies, corroborated these findings. This network meta-analysis demonstrates that SR is the most effective first-line curative treatment for single HCC ≤ 3 cm, followed by RFA in patients with preserved liver function. The limited data on MWA and TACE underscore the need for further studies.