With the rapid introduction of novel breast cancer therapies, recognizing and managing side effects is essential to maintain adherence and improve outcomes. As novel oral endocrine therapies and combination strategies including targeted agents have prolonged progression and in some cases disease-free survival, early recognition and appropriate management of these toxicities is critical to optimize quality of life. Dermatologic adverse events are frequently associated with novel breast cancer therapies including immune checkpoint inhibitors (ICIs), targeted therapies, and antibody-drug conjugates (ADCs). These include various rashes, stomatitis, and alopecia, necessitating multidisciplinary dermatologic intervention to allow for prompt management of cutaneous toxicities and continuation of oncologic therapy. Targeted breast cancer therapies, including ADCs, can also induce ocular adverse events (OAEs), such as corneal pseudomicrocysts which lead to blurry vision and eye pain. Current preventative therapies have had limited success for these OAEs, necessitating dose interruptions. Although anthracycline-based chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy are associated with an increased risk of heart failure and left ventricular (LV) dysfunction, novel breast cancer therapies including ADCs, HER2 tyrosine kinase inhibitors, cyclin-dependent kinase 4 and 6 inhibitors, ICIs, and oral selective estrogen receptor degrader are also associated with an increased risk of LV dysfunction, heart failure, corrected QT prolongation, myocarditis, and bradycardia. This review provides a comprehensive overview of novel and emerging breast cancer therapy toxicities, with suggested management strategies to prevent and mitigate these adverse events. Through a multidisciplinary approach involving preventative strategies, monitoring, proactive interventions, providers can minimize symptom burden and improve patient adherence, ultimately improving breast cancer outcomes.

New technologies and innovations are changing the future of melanoma care. Teledermatology and skin screening mobile apps aided by artificial intelligence (AI) diagnostic support could assist in closing disparity gaps in melanoma early detection and access to specialty care. Although the field of AI in dermatology has exploded over the past decade, prospective validation of available algorithms using real-world, multimodal data sets has shown performance decline, limiting their current use in clinical practice. Newer methodological approaches have focused on how AI can augment clinical decision making to speed diagnosis and care delivery-and whether the model output results in a favorable change for the patient. Selective BRAF and MEK inhibitors have an established role in the adjuvant and metastatic setting for the approximately 50% of patients whose melanomas harbor a BRAF V600 mutation. Acquired resistance to these agents remains a challenge, however. For other driver mutations, including class II and III BRAF mutations, alterations in NRAS and CDKN2A, novel agents and combinations are demonstrating promising activity. At least 50% of patients with metastatic melanoma do not derive long-term benefit from immune checkpoint inhibitors (ICIs). Adoptive cellular immunotherapy with tumor infiltrating lymphocytes offers the possibility of a durable response for a minority of these patients. Potentially more effective and better tolerated T-cell therapies are being evaluated in clinical trials.

Given the graft-versus-leukemia effect observed with allogeneic hematopoietic stem cell transplantation in refractory or relapsed acute myeloid leukemia (AML), immunotherapies have been explored in nontransplant settings. We applied a multiomic approach to examine bone marrow interactions in patients with AML treated with pembrolizumab and decitabine. Using extensively trained nuclear and membrane segmentation models, we achieved precise transcript assignment and deep learning-based image analysis. To address read-depth limitations, we integrated single-cell RNA sequencing with single-cell spatial transcriptomics from the same sample. Quantifying cell-cell distances at the edge level enabled more accurate tumor microenvironment analysis, revealing global and local immune cell enrichment near leukemia cells postpembrolizumab treatment, potentially linked to clinical response. Furthermore, ligand-receptor analysis indicated potential alterations in specific signaling pathways between leukemia and immune cells following immunotherapy treatment. These findings provide insights into immune interactions in AML and may inform therapeutic strategies.

Lung cancer remains the leading cause of cancer-related death globally, with metastasis driven by circulating tumor cells (CTCs)-particularly clusters-being a major treatment challenge. Despite their critical role, the biological differences between single CTCs and CTC clusters remain unclear. Here, we comprehensively compared their behavioral, transcriptomic, and proteomic profiles in lung cancer models. Compared with single cells, CTC clusters present enhanced metastatic potential, greater survival in the bloodstream and increased resistance to microenvironment. Mechanistically, the Src/FN1 pathway is centrally activated in clusters, promoting intercellular cohesion and protecting against immune clearance and stress in circulation. Pharmacological inhibition of Src with the clinical inhibitor KX2-391 disrupted clustering, impaired CTC survival, and reduced metastasis in preclinical models. Our findings identify the Src/FN1 pathway as a key vulnerability in CTC cluster-driven metastasis, suggesting that Src inhibitors are promising therapeutic strategies to disrupt clustering and improve outcomes in patients with metastatic lung cancer.

Metastasis represents a crucial cancer progression and is promoted by cancer-associated fibroblasts (CAFs). Modulating CAFs in distant metastasis is challenging due to their diverse phenotypes and the lack of effective delivery strategies. Inspired by the tropism of tumor extracellular vesicles (Evs) expressing specific integrins toward fibroblasts, we developed a labeling strategy for both tumors and tumor-derived Evs. Our modified nanoliposomes, by hitchhiking on these labeled Evs, concentrated in CAFs at distant metastatic sites while simultaneously targeting the labeled tumor. This Ev-hitchhiking strategy, in combination with the loaded drugs ATRA and lenvatinib, efficiently regulated the myogenic and inflammatory characteristics of CAFs, remodeled the metastatic microenvironment, and suppressed tumor growth and metastasis. The labeling and Ev-hitchhiking approach holds promise for enhancing tumor elimination and modulating CAFs or other Ev-activated cells in distant metastasis, offering a potential breakthrough in cancer therapy.

Myeloma bone disease, a complication of multiple myeloma (MM), is characterized by impaired osteogenic function of bone marrow stromal cells (BMSCs) and can be an indicator of disease progression. The underlying mechanisms driving BMSC dysfunction are not yet fully understood. This work investigated MM cell interaction with BMSCs, finding that BMSC ciliogenesis is inhibited in the presence of myeloma cells. We demonstrated that direct interaction between myeloma cells and BMSCs through CD40-CD40L led to BMSC down-regulation of sentrin-specific protease 1 (SENP1), a cysteine protease that removes small ubiquitin-like modifier (SUMO) posttranslational modifications. SENP1 down-regulation led to increased SUMOylation of oral-facial-digital syndrome type 1 protein (OFD1), a centriole and centriolar satellite protein, at K931. Increased SUMOylation led to increased OFD1 protein stability and localization at centriolar satellites of primary cilia and decreased ciliogenesis. Consequently, BMSCs lacking primary cilia became desensitized to shear stress stimulation and decreased Hedgehog signaling activation. This cascade of events resulted in inhibited ciliogenesis and osteogenesis in myeloma-BMSC-interacting models, in Prx1CreCd40lf/f mice, and in clinical samples. Treatment with an anti-CD40 neutralizing antibody effectively mitigated bone disruption and tumor burden in the Vk*MYC and SCID (severe combined immunodeficient)-hu mouse models of MM. Overall, our study provides experimental insights into BMSC dysfunction in MM and suggests that targeting the CD40-SENP1-OFD1 axis could hold promise for MM treatment in clinical settings.

Programmed death-ligand 1 (PD-L1) expression in various tumors is known to correlate with the efficacy of immune checkpoint inhibitors; however, evaluation of PD-L1 expression in thymic epithelial tumors (TETs) using multiple antibodies are limited. We retrospectivity evaluated PD-L1 expression in thymomas and thymic carcinomas using two antibodies, SP142 and SP263, and compared their expression rates in each type of TETs.

Exploring the clinical differences between papillary thyroid micarcinoma (PTMC) and papillary thyroid carcinoma (PTC), optimizing clinical decision-making pathways, and reducing excessive medical behavior while ensuring therapeutic efficacy.

Despite extensive efforts to develop strategies to inhibit cancer metastasis-the leading cause of cancer-related deaths-progress has been limited in recent decades. Epithelial-to-mesenchymal transition (EMT) initiates metastasis by enhancing the migratory capacity and plasticity of cancer cells, enabling them to escape the primary tumor site. Identifying vulnerabilities unique to mesenchymal cancer cells is, therefore, critical for developing effective antimetastatic therapies. Our prior research has highlighted the crucial role of the Golgi apparatus in EMT-driven cancer cell motility and metastasis. In this study, we investigated the antimigratory effects of various Golgi-disrupting compounds and identified Monensin, a polyether ionophore antibiotic, as a potent migration suppressor in mesenchymal non-small cell lung cancer (NSCLC) cells. Monensin treatment increases the pH within the Golgi lumen, inducing rapid exocytosis of the promigratory Golgi scaffold protein Golgi Integral Membrane Protein 4 (GOLIM4). GOLIM4 plays a key role in regulating cell motility and adhesion by modulating the post-Golgi trafficking of Talin 1 (TLN1), an essential focal adhesion component. Furthermore, we found that both GOLIM4 and TLN1 are highly expressed in mesenchymal cancer cells and are direct targets of microRNA-200b, a microRNA that is suppressed during EMT. Treatment with Monensin or depletion of GOLIM4 or TLN1 significantly impaired the migratory activity of mesenchymal NSCLC cells. In summary, this study demonstrates that Monensin exhibits potential antimetastatic activity by disrupting the promigratory GOLIM4-TLN1 axis in mesenchymal NSCLC cells.

Neuroblastoma (NB), a common pediatric cancer, is often associated with poor prognosis due to resistance to conventional therapies. Abemaciclib, a selective inhibitor of CDK4/6, is known for its ability to block cell cycle progression and induce cell death in various cancer types. In this study, we explore its potential therapeutic impact on NB by assessing its effects on cell proliferation, apoptosis, and the regulation of microRNAs (miRNAs) that are related to NB progression. Antiproliferative effect of abemaciclib, doxorubicin, cisplatin, and temozolomide (TMZ) were detected by MTT method. Combinations of abemaciclib-doxorubicin, abemaciclib-cisplatin, and abemaciclib-TMZ were also investigated by applying IC50 doses of the drugs for 24 h. ELISA and flow cytometry were performed for apoptosis detection, and for cell cycle analysis, flow cytometry was used. The expression levels of eight apoptosis, threee tumor suppressors, two oncogenes, and nine cell cycle-related genes were analyzed by quantitative PCR. Moreover, the expression levels of five NB-related miRNAs were determined. IC50 doses of abemaciclib, doxorubicin, cisplatin, and TMZ were found to be 4.757, 1.958, 34.21, and 240.7 uM in the 24 h, respectively. The combination of the drugs increased apoptosis and decreased cell migration and colony formation rates. The highest expression level difference was observed in PUMA when control and dose groups were compared. Increased expression levels of hsa-mir-18a-5p and hsa-miR-124-3p were detected in all drug-treated groups compared to the control group. Our results highlight the potential of abemaciclib as a promising treatment strategy for NB, particularly when used in combination with other therapies to overcome resistance and improve clinical outcomes.

Hepatocellular carcinoma (HCC) is the primary cause of cancer-related mortality in the world. Cytochrome P450 2E1 (CYP2E1) plays a key role in metabolizing xenobiotics and toxic substances. The attempts to target CYP2E1 with inhibitors have yielded limited success in cancer treatment. Loss and gain-of-function experiments were performed to investigate the effects of CYP2E1 on HepG2 and Hepa 1-6 cells. Migration, invasion, intracellular reactive oxygen species (ROS) accumulation, and mitochondrial membrane potential were assessed in HepG2 cells. In vivo histopathological alterations were studied in DEN-administered rat models. Western blotting was performed to evaluate the mechanistic activation of the Wnt/β-catenin signaling pathway. In our pursuit, to elucidate the impact of CYP2E1 in carcinogenesis we revealed that in vitro, overexpression of CYP2E1 enhances the migration, invasion, increases the accumulation of intracellular ROS, and reduces the loss of mitochondrial membrane potential of HepG2 cells. In contrast, siRNA-mediated silencing of CYP2E1 produced the opposite effects. Histopathological analysis of liver sections showed pathological features such as clear cell foci, bile duct proliferation, inflammatory cell infiltration and nodule formation. In vitro and in vivo, mechanistic analysis demonstrated that CYP2E1 overexpression significantly activated the Wnt/β-catenin signaling pathway in HCC cells, as evidenced by increased protein levels of β-catenin, LEF, Cyclin D1 and survivin in immunoblot study. In vivo increased β catenin, LEF and GPC3 enhance the carcinogenicity as revealed in immunohistochemistry results. Altogether, the above findings indicates that CYP2E1 has a pivotal role in the pathogenesis and progression of HCC identifying it as a potential target for liver cancer treatment.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer, and has a high recurrence rate. RING finger transmembrane-domain containing protein 2 (RNFT2) is a RING-finger E3 ubiquitin ligase that exerts oncogene functions in multiple malignant tumors such as bladder cancer and gastric cancer. However, RNFT2's role in TNBC is still unclear. Here, we investigated RNFT2's function and mechanism in TNBC. RNFT2 expressions in different stages of breast cancer were evaluated using the Gene Expression Profiling Interactive Analysis database. Overall survival (OS) in TNBC patients with high RNFT2 expressions was assessed with the Kaplan-Meier plotter database. Meanwhile, RNFT2 expressions in TNBC cells and tissues were determined using Western blot and quantitative real-time PCR. The relationship between RNFT2 and TNBC patients' OS rates was examined with Kaplan-Meier curve analysis. The correlation between RNFT2 expressions and TNBC clinicopathological data was estimated by the chi-square test. Moreover, RNFT2 functions in TNBC were determined using loss-of-function assay, Cell Counting Kit-8 analysis, Transwell, and tube formation assay. Furthermore, RNFT2's mechanism in TNBC was evaluated by prediction software, dual-luciferase reporter assay, and rescue experiments. Additionally, RNFT2's roles in TNBC in vivo were identified with cell-derived xenograft, hematoxylin-eosin staining, and immunohistochemical assays. RNFT2 was elevated in breast cancer, and owned different degrees of overexpression in breast cancer at different stages. Meanwhile, OS of TNBC patients with high RNFT2 expressions was poor. Also, RNFT2 expressions were positively correlated with size, TNM stage, and lymph node metastasis of TNBC. Functionally, silencing RNFT2 repressed TNBC cell proliferation, invasion, and angiogenesis. Mechanistically, miR-211-5p targeted RNFT2, and RNFT2 was negatively regulated by miR-211-5p in TNBC cells. Rescue assays further validated that miR-211-5p overexpression restrained TNBC cell proliferation, invasion, and angiogenesis, yet these impacts were abolished after RNFT2 overexpression. Meanwhile, animal experimental data further implied that RNFT2 knockdown reduced TNBC cell proliferation in vivo. RNFT2 facilitated TNBC development and predicted its adverse outcomes.

Long non-coding RNA MINCR performs a tumor-promoting role in various cancers. Accordingly, this research analyzed whether MINCR exerted tumor-promoting effects and facilitated gemcitabine (GEM) resistance in BC. MINCR, microRNA (miR)-876-5p, ZEB1, and PHGDH expression was detected in BC tissues and cells. Following the construction of GEM-resistant cells, MINCR expression was examined with RT-qPCR. Gain- and loss-of-function assays were conducted in GEM-resistant cells, followed by the measurement of cell proliferation, invasion, and apoptosis. The relationships among MINCR, miR-876-5p, and ZEB1 were assessed with dual-luciferase and RIP assays. Subcutaneous tumor formation in nude mice was conducted for in vivo corroboration. MINCR was up-regulated in BC tissues and cells and GEM-resistant BC cells. miR-876-5p expression was poor and ZEB1 and PHGDH expression was abundant in BC tissues. Mechanistically, MINCR enhanced ZEB1 expression in BC cells via competitive binding to miR-876-5p, and ectopic ZEB1 induced PHGDH up-regulation. MINCR silencing diminished proliferation and invasion while accelerating apoptosis in GEM-resistant BC cells, which was further advanced by miR-876-5p overexpression but nullified by ZEB1 overexpression. Meanwhile, MINCR silencing or miR-876-5p overexpression synergized with GEM to depress BC growth in vivo. MINCR silencing impedes GEM resistance in BC through the miR-876-5p/ZEB1/PHGDH axis.

Nodular melanoma (NM) is considered one of the most aggressive forms of skin cancer, accounting for approximately 10-15% of all melanoma cases. It tends to grow quickly and spread deeper into the skin's layers, providing fewer opportunities for early detection. NM often carries a poor prognosis due to local invasion and frequent distant metastases. BRAF mutations are frequently found in melanoma, with the most common mutation being a single-point mutation at codon 600 (typically V600E).

miR-429 is a tumor suppressor that has been observed in various cancers. The exact mechanism by which miR-429 affects salivary adenoid cystic carcinoma(SACC) is not fully understood. Initially, the expression of miR-429 and zinc finger E-box-binding homeobox 1 (ZEB1) in tumor tissues and matched adjacent non-tumor tissues of SACC patients were inspected by quantitative real-time polymerase chain reaction. Next, CCK-8, wound healing, transwell, and dorsal root ganglion (DRG) co-culture models were used to explore the effects of miR-429 on SACC cell proliferation, migration, invasion, and perineural invasion (PNI). Finally, the downstream target genes of miR-429 were screened and validated through bioinformatics analysis and dual-luciferase reporter analysis, and the regulatory role of miR-429 on epithelial-mesenchymal transition (EMT) in SACC cells was explored. miR-429 was poorly expressed while ZEB1 was substantially expressed in SACC tumor tissues. Elevated levels of miR-429 led to a significant suppression of SACC cell of proliferation, migration, invasion, and PNI. ZEB1 was screened and validated as a downstream target gene of miR-429. High concentrations of miR-429 also markedly lowered the expression of ZEB1 in SACC cells, thereby inhibiting EMT. These results suggest that miR-429 is lowly expressed in SACC, may suppress progression and metastasis of SACC cells, and is associated with ZEB1 and the EMT pathway.

Colon cancer remains a leading cause of cancer-related mortality globally, highlighting the urgent need for advanced diagnostic methods to improve early detection and patient outcomes.

Ovarian cancer is a highly aggressive malignancy influenced by complex molecular interactions, including those involving long non-coding RNAs. RBM5-AS1, a nuclear-retained lncRNA, interacts with GCN5 to acetylate PGC-1α, thereby enhancing the Warburg effect. Although fasting is known to exert antitumor effects by modulating lncRNAs and activating PGC-1α, its impact on the RBM5-AS1/GCN5 axis in ovarian cancer remains underexplored. This study evaluates the therapeutic efficacy of RBM5-AS1 knockdown and GCN5 inhibition under fasting-mimicked conditions in SKOV3 cells.

The current study seeks to investigate the clinical outcomes of combining immune checkpoint blockade, anti-angiogenesis, and chemotherapy in neoadjuvant treatment for individuals diagnosed with locally advanced (high-risk Stage III or initially unresectable Stage III) or resectable/unresectable Stage IV colorectal cancer, including metastatic cases.

Esophageal cancer (EC) is still a difficult problem in medicine, depriving many patients of their lives every year. RAD18 and ATM were implicated in cancers including esophageal squamous cell carcinoma (ESCC). However, whether RAD18/ATM axis influences ESCC progression remains unclear.

To review, evaluate and summarize data from the literature presenting the risk of developing gallbladder cancer in patients with PSC and gallbladder polyps.