Systemic therapy for recurrent and metastatic salivary gland malignancies (SGMs) remains a major therapeutic challenge. Traditional chemotherapy offers modest response rates with limited durability, and its role is largely palliative. The most meaningful advances have occurred in biomarker-selected subgroups: androgen receptor blockade for AR-positive salivary duct carcinoma and HER2-directed therapy for HER2-positive tumors have demonstrated superior response rates and survival (often exceeding 50%), compared with the single digit response rates seen with unselected chemotherapy or tyrosine kinase inhibitors. Small-molecule tyrosine kinase inhibitors such as lenvatinib and axitinib may provide disease stabilization in adenoid cystic carcinoma, although tumor shrinkage is uncommon and toxicity limits their long-term use. Immunotherapy as a single agent has been disappointing, but durable responses in select patients and modest activity with combination regimens suggest it may have a future role when rationally paired with other agents. In our practice, comprehensive molecular profiling is essential at the time of recurrence to identify actionable alterations, prioritize targeted therapy where available, and guide clinical trial enrollment. For most patients without a targetable alteration, platinum-based combinations remain the pragmatic choice, though expectations for benefit should be tempered. Future strategies will likely hinge on optimizing biomarker-driven therapies, expanding access to antibody-drug conjugates, and pursuing collaborative trial designs to overcome the rarity and heterogeneity of these tumors.

There are 2 mainstays of therapy for malignant or aggressive brain tumors that are effective in controlling growth: systemic treatments such as immunotherapy and chemotherapy and radiation including brachytherapy. Prior versions of brain brachytherapy have proven challenging to use due to adverse effects, resulting in limited application of this therapy. The most recent development in brain brachytherapy is a tile-based radioactive device, GammaTile®, that is implanted at the time of tumor removal. GammaTile is FDA-approved for malignant brain tumors as well as recurrent brain tumors and addresses all the nuances of prior versions. This literature review provides neuroscience nurses with a working understanding of tile-based brain brachytherapy. METHODS: Searches were conducted across multiple medical databases including PubMed, CINAHL, and EBSCO, using combinations of keywords related to brachytherapy, GammaTile, and brain tumors to identify relevant background and descriptive literature, and using combinations of keywords, nursing care, brachytherapy, brain, head, and malignancies, to identify relevant nursing care literature. RESULTS: Fifteen recently published articles were deemed relevant to provide neuroscience nurses with a working knowledge of tile-based brain brachytherapy. Literature on the nursing care of patients receiving tile-based brain brachytherapy is scarce, and only 2 articles published within the past 40 years specific to nursing care of patients receiving brain brachytherapy were discoverable. CONCLUSION: As the number of GammaTile cases and centers across the country continue to mount, neuroscience nurses need to have a working knowledge of this type of tile-based brain brachytherapy. There are significant differences in the care of patients after implantation of tile-based radiation therapy like GammaTile compared with prior brachytherapy products. These differences have implications for nurse and patient safety and patient/family education.

Anlotinib is a multi-target tyrosine kinase inhibitor that has been approved in China as a third-line treatment for advanced non-small cell lung cancer. It exerts anti-tumor effects by inhibiting tumor growth and tumor angiogenesis, and its toxicity also arises from this mechanism. Anlotinib can damage vascular endothelium, thereby inducing cardiovascular toxicity, which leads to hypertension, hyperlipidemia, accelerated atherosclerosis, and the initiation of atherosclerotic cardiovascular disease, ultimately resulting in life-threatening cardiovascular events. To the best of our knowledge, this study is the first case report documenting the development of hypertension, hyperlipidemia, hypothyroidism, subsequent discovery of bilateral renal artery stenosis, and acute myocardial infarction in a young patient receiving anlotinib treatment. This showed anlotinib may accelerate systemic large/medium-sized artery atherosclerosis in the context of complex tumor therapy, causing life-threatening cardiovascular events. Besides, it highlights the necessity of regular monitoring of relevant indicators during follow-up for patients undergoing anlotinib therapy, enabling early detection of warning signs and timely intervention.

Glutathione-responsive and mitochondria targeting enhanced photodynamic therapy and cascade-triggered carbon monoxide release for all-in-one tumor therapy.

pH-triggered Schottky heterojunctions for NIR-II-activated and tumor-specific pyroelectrodynamic and photothermal therapy.

The extracellular matrix shapes tumor architecture, cell behavior and therapy response. Here, we identify aberrant activation of the receptor tyrosine kinase VEGFR2 as a driver of tumor-promoting ECM remodeling in melanoma and ovarian cancer. ECM alterations in terms of composition and organization were observed in Sk-Mel-31 melanoma xenografts expressing the oncogenic VEGFR2R1032Q and in ovarian tumors with VEGFR2 hyperactivation. Down-modulation of VEGFR2 normalized ECM architecture. Decellularized ECM from VEGFR2R1032Q melanoma cells directly modified the behavior of VEGFR2WT tumor cells, increasing monolayer fluidity and mitochondrial activation. Transcriptomic profiling revealed a dysregulation of genes involved in ECM structure and remodeling, mediated by the PI3K-AKT and ERK pathways. Pharmacological inhibition of VEGFR2 with tyrosine kinase inhibitors, such as lenvatinib, partially reverted ECM alterations in vitro and in vivo, reducing matrix deposition and modifying its organization. These data identify VEGFR2 as a regulator of tumor ECM dynamics and suggest that its inhibition may restore ECM organization, offering a therapeutic strategy to reprogram the tumor microenvironment and limit cancer progression.

ABSTRACT Sonodynamic therapy, as a deep penetrating therapy method with high therapy efficacy, is garnering attention in the field of tumor therapy. Nevertheless, the trade‐off between high sonodynamic efficacy and stability is difficult to balance for conventional sonosensitizers, which impedes their clinical translation. Exploring the sonodynamic performance of novel materials is imperative to synchronously achieve these two aims. Two‐dimensional (2D) metal borides (MBene) possess enormous application potential in biotechnology fields, but so far there are few studies on sonodynamic therapy research. In this work, two types of metal boride nanosheets, orthorhombic and hexagonal molybdenum boride (MoAlB‐MoB and Mo 4/3 B 2‐x T z ), are synthesized, and their properties are characterized to understand the structure‐properties relationship. The MBene nanosheets demonstrate superior and stable sonodynamic efficacy compared with commercial sonosensitizers (TiO 2 and indocyanine green) and a nanosheet sonosensitizer (Mo 2 C MXene). By delivering via microneedle, the MBene nanosheets can significantly inhibit tumor growth with a high precision through sonodynamic reactions. Mechanistic investigations reveal that immunity is activated and long‐term immunity memory is established to suppress tumor. The structure‐function relationship of MBene nanosheets are further simulated. This work elucidates the therapeutic potential and mechanistic foundations of MBene‐based sonodynamic therapy, establishing a promising platform for sonodynamic cancer therapy.

Chlorella-based bioactive oxygen generator for sustained tumor hypoxia alleviation and combined-modality tumor therapy.

Recent advances have significantly expanded our understanding of the roles played by mitochondria and tumor innervation in tumorigenesis. Once viewed primarily as contributors to energy production and metastatic dissemination, mitochondria are now recognized as central players in broader processes, including immune modulation within the tumor microenvironment, therapy resistance, and metastatic progression. Interestingly, the findings have eventually converged, and evidence now shows that mitochondria can be transferred from neurons to tumor cells, resulting in enhanced invasiveness. While these discoveries are promising, they also present new challenges that must be addressed. As the interconnection between neuroscience, oncology, and immunology continues to deepen, these insights open new avenues for the development of innovative therapeutic strategies. This review explores the most recent findings regarding nerve-cancer interaction, with a specific focus on genitourinary cancers, highlights their emerging intersections, and discusses how these insights may inform the development of novel therapeutic targets for cancer treatment.

Background/Objectives: Cancer-associated fibroblasts (CAFs) are key stromal mediators of breast tumor progression and therapy resistance. Carvacrol, a dietary monoterpenic phenol, exhibits antiproliferative activity in cancer cells, but its effects on primary human breast CAFs remain unclear. This study aimed to determine whether carvacrol selectively induces mitochondria-related apoptotic signaling in breast CAFs while sparing normal fibroblasts (NFs). Methods: Primary fibroblast cultures were established from invasive ductal carcinoma tissues (CAFs, n = 9) and nonmalignant breast tissues (NFs, n = 5) and validated by α-SMA and FAP immunofluorescence. Cells were exposed to 400 μM carvacrol. Apoptosis was assessed by TUNEL assay and BAX/BCL-XL Western blotting. Changes in signaling pathways were evaluated by analyzing PPARα/NF-κB, sirtuin (SIRT1, SIRT3), autophagy-related markers (LAMP2A, p62), and matrix metalloproteinases (MMP-2, MMP-3). In silico molecular docking and 100-ns molecular dynamics simulations were performed to examine interactions between carvacrol and caspase-3 and caspase-9. Results: Carvacrol induced a pronounced, time-dependent apoptotic response in CAFs, with TUNEL-based viability declining to approximately 10% of control levels by 12 h and a marked increase in the BAX/BCL-XL ratio. In contrast, NFs exhibited minimal TUNEL positivity and no significant change in BAX/BCL-XL. In CAFs, but not NFs, carvacrol reduced PPARα expression and NF-κB nuclear localization, increased SIRT1 and SIRT3 levels, selectively suppressed MMP-3 while partially normalizing MMP-2, and altered autophagy-related markers (decreased LAMP2A and accumulation of p62), consistent with autophagic stress and possible impairment of autophagic flux. Computational analyses revealed stable carvacrol binding to caspase-3 and caspase-9 with modest stabilization of active-site loops, supporting caspase-dependent, mitochondria-related apoptosis. Conclusions: Carvacrol selectively targets breast cancer-associated fibroblasts by inducing mitochondria-related apoptotic signaling while largely sparing normal fibroblasts. This effect is accompanied by coordinated modulation of PPARα/NF-κB, sirtuin, autophagy, and MMP pathways. These findings support further evaluation of carvacrol as a microenvironment-directed adjunct in breast cancer therapy.

Ionizing radiation (IR) is used to treat more than half of cancer patients because it induces DNA double-strand breaks and triggers apoptosis. IR also damages other nucleic acids, lipids, proteins and cellular organelles, initiating additional complex cellular responses. Some of these responses are transient, while others can become permanent and lead to changes in cellular identity. This review focuses on cell fate plasticity, defined as the conversion of one cell type into another, during recovery after IR-induced damage. We recognize that this process likely occurs along a continuum and may be reversible. We will distinguish cell fate plasticity from molecular or phenotypic plasticity, such as epigenetic modifications, transcriptomic shifts, altered signalling, morphological changes or acquisition of migratory behaviour, all of which are clinically relevant but do not constitute a change in cell type for the purposes of this review. Importantly, cell fate plasticity can enable cancer cells to acquire stem-like properties, which has major implications for tumour progression and therapy resistance.

Computational versus experimental approach toward thermal therapy of tumor using magnetite nanoparticles with multiturn coil excitation

Correction: Bacteria‑triggered liposomes for synergistic tumour therapy based on the hypoxic microenvironment

Abstract Background Tumor-associated macrophages (TAMs) frequently adopt an M2-like, immunosuppressive state that promotes tumor growth and therapy resistance. Reprogramming TAMs toward a pro-inflammatory M1 phenotype is a promising strategy to remodel the tumor microenvironment (TME) and enhance treatment responses. We evaluated an iron(III)–quercetin complex (IronQ) as a macrophage-directed, magnetic resonance imaging (MRI)-visible theranostic. Methods IronQ stability was tested in protein-containing media by dynamic light scattering (DLS). Biocompatibility was assessed in fibroblasts (MRC-5), THP-1–derived macrophages, and non-small-cell lung cancer (NSCLC) cell lines (A549, H460). Cellular uptake was examined by Prussian blue staining and in vitro MRI. Reactive oxygen species (ROS; DCFH-DA), ERK/NF-κB activation (Western blot), and polarization markers (flow cytometry, qRT-PCR, ELISA) were quantified after IronQ exposure. Functional anti-tumor effects were evaluated in non-contact Transwell co-cultures and in 3D tri-culture spheroids (tumor cells, fibroblasts, macrophages). For imaging, agar-embedded spheroids containing IronQ-labeled macrophages were scanned by T1-weighted MRI. Results IronQ was colloidally stable and well tolerated across cell types within a broad non-toxic window. It accumulated preferentially in macrophages. At low doses, IronQ increased intracellular ROS, activated ERK/NF-κB signaling, upregulated M1 markers ( CD86 , NOS2 , TNFA , IL1B ), and downregulated M2 markers ( CD206 , TGFB1 , IL10 , CCL18 ); these effects attenuated at higher doses, indicating a biphasic response. Functionally, IronQ repolarized IL-4–primed M2 macrophages and indirectly reduced tumor viability in Transwell assays. In 3D spheroids, IronQ limited growth and shifted the secretome toward higher TNF-α and lower IL-10, with IL-6 unchanged. As an imaging agent, IronQ produced dose-dependent T1 hyperintensity in labeled cells and yielded positive T1 signal in spheroids containing IronQ-labeled macrophages. Conclusions IronQ integrates macrophage-selective uptake, actionable M1 repolarization within a defined dose window, and positive-contrast MRI visibility. These properties support its development as a cost-efficient, multifunctional platform for TAM-focused cancer immunotherapy and image-guided response monitoring.

Lactate, a major product of glycolysis, accumulates abundantly in the tumor microenvironment (TME), serving not only as a hallmark of metabolic dysregulation but also as a key driver of immunosuppression. In recent years, lysine lactylation (Kla), a novel post-translational modification (PTM), has been identified, linking lactate metabolism closely with epigenetic regulation. Current studies indicate that lactylation modulates gene transcription and metabolic pathways in tumor cells while broadly influencing immune cell functions. For example, histone lactylation in macrophages promotes M2 polarization, enhancing immunosuppressive phenotypes; T cells, natural killer (NK) cells, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs) may also be regulated by lactylation, thereby affecting anti-tumor immune responses and the efficacy of immune checkpoint inhibitors. As the mechanistic understanding of lactylation deepens, its roles in tumor immune evasion and therapy resistance are becoming increasingly evident. Targeting lactate metabolism and lactylation-related enzymatic processes, potentially in combination with immunotherapy, may represent a promising therapeutic strategy. This mini-review summarizes recent advances in lactylation research in tumor immunity and discusses its potential clinical implications and future directions.

Abstract Introduction: Aside from standard surgical resection followed by chemo/radiation therapy, there is a dearth of effective therapies for tumors of the central nervous system (CNS) despite increasing understanding of the molecular mechanisms driving oncogenesis and progression. Antisense oligonucleotides (ASOs) have emerged as a powerful method to target disease-causing transcripts through sequence-specific translational blocking or degradation. However, while it is known that oncogenic fusions drive some CNS tumors, few studies have investigated and characterized the landscape of oncogenic fusions and variation in breakpoints, pertinent for the translation of ASOs into a viable therapy. Methods: We performed retrospective analysis of CNS tumors from 1690 patients profiled at the Children’s Hospital of Philadelphia as part of routine clinical molecular workup. Additionally, we have developed an ASO-based therapeutic platform to design ASOs which target the fusion junctions and validate their efficacy in eliminating the targeted fusion transcripts. Results: Our cohort spanned both pediatric (980/1690) and adult (710/1690) ages (range = 0 - 91) and histologic subtypes. In total, 21% of CNS tumor patients (354/1690) harbored an oncogenic fusion; Grade 1 = 38% (218/567), Grade 2 = 6% (12/211), Grade 3 = 12% (22/176), and Grade 4 = 13% (75/570). Fusions were most common in glial neoplasms (27%, 328/1213) followed by ependymal tumors driven by ZFTA rearranged supratentorial ependymoma (13%, 20/150), and mesenchymal tumors (28%, 5/18). The most common fusions included BRAF in Grade 1 tumors and MET and EGFR in Grade 4 tumors. NTRK1/2/3 fusions, which have promiscuous partners spanned all grades, and FGFR1/2/3 fusions were only found in Grade 1 or 4 tumors, most often fused to TACC1 or TACC3. BRAF, NTRK2, and MET fusions had the highest number of unique partners. Investigating unique transcripts, nearly all fusions had conserved breakpoints except for KIAA1549::BRAF fusions, which had 15 unique transcripts. Interestingly, while ZFTA::RELA fusions had relatively conserved breakpoints, all tumors expressed at least 2 unique transcripts (1 major), suggesting co-existence of different chimeric isoforms. MYB::QKI fusions, identified in low-grade gliomas, was selected as a pilot target to evaluate the ASO-based therapeutic platform. A list of five ASOs were tested in mammalian cells expressing MYB::QKI fusion reporters. The most effective ASO was found to reduce MYB-QKI reporter fluorescent signal by ∼83% and fusion transcript level by ∼63% compared to the negative ASO, as measured by cellular imaging and RT-qPCR, respectively. Conclusion: In the current landscape, where therapeutic options for fusion-driven tumors in the CNS are limited, this ASO-based therapeutic platform presents a new avenue for developing personalized nucleic acid-based therapies aimed at improving clinical outcomes for individuals with CNS tumors. Citation Format: Hyojeong Hwang, Jinhua Wu, Jeffery Schubert, Meha Patel, Natali Naveh, Netta Golenberg, Minjie Luo, Yiming Zhong, Lea F Surrey, Marilyn M Li, Monica Pomaville, Kathy Fange Liu, Derek Wong. Transcriptomic landscape of fusion-driven CNS tumors for the design and validation of junction-specific antisense oligonucleotide-mediated targeting of fusion oncogenes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Fusion-Positive Cancer: From Discovery to Therapy; 2026 Jan 13-15; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(1_Suppl):Abstract nr A006.

Sarcomas are rare malignancies of mesenchymal origin, characterized by significant biological and clinical heterogeneity. Many subtypes demonstrate limited sensitivity to standard systemic treatments, including immune checkpoint inhibitors. Cell therapy has emerged as a promising strategy, with the potential of durable clinical responses seen with genetically-engineered T-cell receptor T-cell therapies (TCR-T) such as those targeting the cancer-testis antigen MAGE-A4 in synovial sarcoma, leading to the US Food and Drug Administration approval of afamitresgene autoleucel in 2024. This constituted only the second approval of a cell therapy in a solid tumor following lifileucel in melanoma and demonstrated the potential of cell therapies in sarcomas. This review provides the current landscape and growing potential of cell therapies in sarcomas, including TCR-T, chimeric antigen receptor-T cells, tumor-infiltrating lymphocytes, natural killer (NK) cells, and mesenchymal stromal cells. However, the broader application of these therapies is hindered by the lack of targetable sarcoma-restricted immunogenic epitopes, spatiotemporal intratumoral heterogeneity, and a profoundly immunosuppressive tumor microenvironment that impedes effector-cell trafficking, expansion and persistence. While cell therapies hold promise for integration into precision medicine approaches for sarcomas, their successful implementation will require careful evaluation of clinical feasibility, logistical considerations and cost-effectiveness to optimize patient outcomes.

Bicyclic peptides, which integrate the advantageous properties of small molecules and antibodies, have emerged as a promising class of therapeutic candidates. In particular, integrin αvβ3 serves as a critical molecular target for cancer diagnosis and therapy. However, the development of bicyclic peptide ligands specifically targeting this integrin remains inadequately explored. To address this gap, we designed and synthesized a series of RGD-containing bicyclic peptides featuring a tryptathionine bridge. Notably, bicyclic peptide 5j incorporates the non-canonical sequence norArg-Gly-Asp, exhibiting high affinity and selectivity toward integrin αvβ3. Molecular dynamics simulations provided insights into the conformational preferences and demonstrated that norArg plays a critical role in determining the selectivity between αvβ3 and αIIbβ3. Employing peptide 5j as the targeting ligand, the peptide drug conjugates P1 showed significant inhibitory effects on the A549 cell line in both, in vitro and in vivo experiments. These data provide important theoretical foundations for the development of αvβ3-targeting bicyclic peptides and offer new options for αvβ3-targeted tumor therapy.

Due to the paucity of validated cell surface osteosarcoma-specific targets, patients with this condition have long been excluded from the benefits of antibody-drug conjugate (ADC) therapy observed in patients with several solid and hematologic malignancies. Our comprehensive surfaceome profiling approach previously identified osteosarcoma-specific cell-surface antigens that are highly expressed in osteosarcomas but minimally expressed in normal tissues. As a result, one such antigen, CADM1, was selected for the generation of an ADC. We tested a CADM1-targeting ADC with a tesirine payload (SG3249) in vitro in osteosarcoma, rhabdomyosarcoma, and neuroblastoma patient-derived xenograft cell lines. In vivo, we tested six CADM1-expressing osteosarcoma patient-derived xenograft models. The CADM1 ADC demonstrated significant antitumor activity in vitro across the osteosarcoma, rhabdomyosarcoma, and neuroblastoma cell lines. Additionally, it effectively reduced tumor volume and extended event-free survival in all six osteosarcoma PDX models tested. Notably, the CADM1 ADC achieved a major complete response in one model (OS2), complete responses in two models (OS1 and OS33), and partial responses in three models (OS9, OS17, and OS31). Based on these results, clinical development of CADM1-targeted therapies for osteosarcoma and other CADM1-expressing pediatric solid tumors may be warranted.

SUMMARYB7-H3 is a cell surface protein overexpressed in many solid tumors and an attractive target for chimeric antigen receptor (CAR) T cell therapy. The most clinically advanced B7-H3 CARs are derived from murine monoclonal antibodies (mAbs) 376.96 and MGA271, which are now in phase1/11trials. However, non-human mAb sequences can provoke immune responses, leading to CAR T-cell rejection and therapeutic failure. Although scFv humanization reduces this risk, residual foreign residues within the variable domains remain. To overcome this limitation, we used in vitro phage display to generate fully human B7-H3-specific scFvs for CAR design. In pancreatic cancer, neuroblastoma, and glioblastoma xenograft models, CAR T cells incorporating the lead human binder Y111 were well tolerated and demonstrated superior antitumor activity compared with 376.96- and MGA271-based CARs. Y111 CAR treatment induced complete responses, tumor rejection, and significant survival benefits, identifying Y111 as a promising fully human B7-H3 CAR for solid tumors.