Volume 27, Issue 2

Metastatic urothelial carcinoma (mUC) is considered an incurable malignancy; however, patient outcomes are improving with the adoption of novel treatments. A significant portion of patients with UC have HER2 overexpression measured by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) or HER2 genomic amplifications and/or mutations detected on next-generation sequencing, making HER2 an attractive therapeutic target. Several clinical trials have assessed the efficacy of HER2-targeted therapies in UC, and trastuzumab deruxtecan has recently been approved as a tumor-agnostic systemic therapy for metastatic solid tumors, including mUC, that are HER2-positive by IHC 3+ expression. Nonetheless, clinical trials of HER2-targeting therapies in mUC have used different assays for the measurement of HER2 positivity, which could affect results. This review summarizes past experiences and delves into the controversies and potential of HER2-targeting therapies, including antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates, in mUC.

Colorectal cancer (CRC) is a prevalent malignancy, and its liver metastasis is a key factor leading to patient death. Research has shown that exosomal microRNA (miRNA) plays an important role as a mediator of communication between tumor cells and other cells in the growth, invasion, and metastasis of cancer cells. It also plays a critical role in the occurrence and development of CRC liver metastasis (CRC-LM). This article reviews the biological functions of exosomal miRNA and explores its significant involvement in the mechanism of CRC-LM. It also focuses on the latest progress of extracellular vesicle miRNA in the study of CRC-LM, providing new ideas and methods for future treatments.

Sebaceous carcinoma (SC) is an aggressive cancer arising from sebaceous glands, rarely occurring in the oral cavity (IOSC). With 21 documented cases, it typically affects the buccal and labial mucosa, tongue, and palate. The cause remains unclear, but Fordyce granules, sebaceous structures in oral mucosa, may play a role in malignancy. IOSC often presents as a painless lump, leading to delayed diagnosis and increased risks of recurrence and metastasis. Early detection and treatment are crucial. Wide local excision (WLE) is the primary treatment, while radiotherapy (RT) is an option for patients unfit for surgery, unwilling to undergo it, or requiring palliative care for advanced cases. RT may also be used pre- or postoperatively to reduce recurrence risks. Cryotherapy and chemotherapy are not standard treatments for IOSC. Regular follow-up is essential for long-term management and to monitor for potential recurrence. The current review provides an updated overview of IOSC, focusing on its clinical presentation, risk factors, pathogenesis, diagnostic approaches, treatment strategies, and prognosis, aims to emphasize the importance of early intervention and a multidisciplinary approach to optimize outcomes.

Theranostics is a technique used in precision oncology to combine focused treatments with diagnostic imaging, thereby enabling tailored cancer treatment. Using modern imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), Theranostics guarantees accurate tumor diagnosis and tailored treatment planning. Radiopharmaceuticals, such as Lutetium-177 (Lu-177) and prostate-specific membrane antigen (PSMA)-targeted therapies, have demonstrated significant clinical enhancements in progression-free and overall survival rates relative to traditional treatments, especially in prostate cancer and neuroendocrine tumors. Emerging technologies such as nanotheranostics and artificial intelligence (AI)-driven tools are enhancing the precision and efficacy of these treatments. However, the widespread application of theranostics is impeded by tumor heterogeneity, elevated prices, and restricted accessibility. Increased research and funding are necessary to address these issues and fully actualize theranostics’ potential to revolutionize cancer detection and therapy. To highlight the above challenges, this review examines diagnostic imaging and therapy advancements, focusing on clinical applications and technologies such as nanotechnology and AI-driven methods.

Objectives To evaluate the safety and efficacy of half-body irradiation (HBI) in improving quality of life, reducing analgesic intake, alleviating pain intensity, and achieving local disease control. We hypothesized that a higher biological effective dose (BED) would increase the objective response rate (ORR) and enhance pain relief. Methods We retrospectively reviewed our mono-institutional database to identify patients with painful widespread bone metastases from solid tumors treated with HBI. Primary outcomes included pain levels, analgesic consumption, and toxicity. Secondary outcomes were ORR, local control (LC), progression-free survival (PFS), and overall survival (OS). Results Twenty-three patients met the inclusion criteria, with 24 treatments administered (one patient underwent HBI twice). Higher doses were given in 9 treatments, with 6 patients receiving a simultaneous integrated boost (SIB). Almost all patients reported immediate pain relief, with 25 % achieving complete pain resolution. Better outcomes were observed in breast cancer patients, with nearly half achieving complete pain relief. Before treatment, 82.6 % of patients used analgesics; after treatment, 42.1 % discontinued medications. Six complete responses were recorded out of 15 imaging assessments, with 5 involving higher doses. Two patients experienced local relapse, neither receiving SIB. Higher doses improved local control and pain relief, though not statistically significant. Five patients died. Three required blood transfusions due to anemia, and two had decreased platelet counts. No additional toxicity was observed in SIB-treated patients. Conclusions HBI is effective for symptom palliation in widespread bone metastases. Incorporating SIB may enhance ORR by increasing BED. Attention to marrow toxicity is needed despite radiotherapy advancements.

Objectives Detecting and diagnosing Lynch syndrome in colorectal cancer patients is essential for enhancing the quality of diagnosis, treatment, and management. This study aims to characterize mismatch repair (MMR) protein expression and MMR gene variants in Vietnamese patients. Methods A total of 218 patients diagnosed with colorectal cancer at the Nuclear Medicine and Oncology Center, Bach Mai Hospital (Hanoi, Vietnam) were included in this descriptive, retrospective study. Tumor tissue samples were evaluated for MMR protein expression. Cases with loss of MMR protein expression underwent genomic sequencing for MMR gene mutations. Results Among 218 colorectal cancer patients, 135 were men (61.9 %) and 83 were women (38.1 %), aged 16–86 years. The prevalence of MMR deficiency (dMMR) was 14.7 %. The expression loss rates of the MLH1, MSH2, MSH6, PMS2, MLH1/PMS2, and MSH2/MSH6 proteins were 9.4 %, 3.1 %, 3.1 %, 21.9 %, 46.9 %, and 15.6 %, respectively. Within the dMMR group, four variants were identified in the MLH1 gene, one in the MSH2 gene, two in the PMS2 gene, and one in the EPCAM gene, and all were classified as germline pathogenic variants associated with Lynch syndrome. Conclusion This is a study to apply next-generation sequencing (NGS) technology to diagnose Lynch syndrome from dMMR cases in Vietnamese colorectal cancer patients. Our research supports the screening and diagnosis of Lynch syndrome through testing using MMR protein expression and assessing pathogenic variants in MMR genes.

Objectives Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. Although bone morphogenetic protein receptor type 1A (BMPR1A) is recognized for its important role in tumor development, the precise mechanism by which it acts in CRC necessitates additional research. Our study aimed to investigate the role and mechanism of BMPR1A in CRC. Methods Using the Gene Expression Profiling Interactive Analysis (GEPIA) database, we analyzed BMPR1A expression in CRC. We investigated the effects of BMPR1A on cell proliferation, migration, invasion, and cell cycle, and the regulation of Smad1. In addition, a mouse xenograft model was established. Results The GEPIA database revealed that elevated expression levels of BMPR1A correlate with higher mortality rates and shorter survival duration in patients with CRC. Following the knockdown of BMPR1A, SW620 and HCT116 cells exhibited a decrease in the rate of value addition, arrest of the cell cycle, and a heightened rate of apoptosis, alongside a reduction in migratory and invasive capabilities. Tumor growth was inhibited after the injection of cells with si-BMPR1A in CRC mouse models. Further investigation demonstrated that SMAD family member 1 (Smad1) is activated by BMPR1A. Inhibition of the BMPR1A/Smad1 pathway was found to block p38 pathway activation and mitigate CRC progression. Conclusions BMPR1A could have a crucial function in the development of CRC through the activation of Smad1, and governs related downstream processes. Targeting BMPR1A provides a foundation for novel therapeutic strategies in CRC.

Objectives We aim to explore the diagnostic value of platelet-based “liquid biopsy” technology for cholangiocarcinoma (CCA), seeking reliable methods for early cancer diagnosis to improve patient prognosis. Methods Bioinformatics methods were utilized to analyze the GEO databases (GSE183635) and (GSE68086), identifying differentially expressed genes and constructing a diagnostic model of CCA using tumor-educated platelet (TEP) RNA expression profiles. GO and KEGG pathway enrichment analysis were performed. Additionally, platelet RNA from CCA patients and controls totaling 60 cases was extracted by qRT-PCR experiments to validate the diagnostic reliability of candidate genes, further confirmed through in vitro experiments. Results A diagnostic model comprising seven platelet genes (CRYM, IFI27, EED, METAP1, RASGRP1, SEC11A, and WDR82) effectively distinguished CCA from controls. Area under curve (AUC) values were 0.862 (training set), 0.875 (internal validation), 0.865 (total internal), and 0.954 (external validation). GO analysis highlighted “non-coding RNA processing,” “nuclear envelope,” and “catalytic activity, acting on RNA.” KEGG pathways included “Ribosome biogenesis in eukaryotes”, “RNA translocation” and “Spliceosome”. qRT-PCR experiments revealed significant differences (p<0.05) in METAP1, SEC11A, WDR82, RASGRP1, and EED gene expression in CCAs, consistent with bioinformatics predictions. CRYM showed significant differences (p<0.001) compared to healthy individuals. WDR82 and CRYM had high diagnostic efficiency (AUC 0.939 and 0.942), surpassing conventional tumor markers (AFP, CEA, and CA19-9). Joint receiver operating characteristics (ROC) analysis yielded an AUC of 0.806, sensitivity of 1.000, and accuracy of 0.833. Conclusions Based on the GEO database, we identified seven TEP RNAs (CRYM, IFI27, METAP1, SEC11A, WDR82, RASGRP1, EED) with strong discriminative ability for CCA, suggesting their potential as reliable non-invasive biomarkers.

Objectives PCSK9 is critical in cholesterol homeostasis and anti-tumor immunity modulation. This study aims to investigate PCSK9’s role in HER2-positive breast cancer (BC) as a potential prognostic marker. Methods The impact of PCSK9 on HER2-positive BC was analyzed by virtue of data from The Cancer Genome Atlas (TCGA). Moreover, PCSK9 expression in tumor cells from 92 HER2-positive patients was assessed through immunohistochemistry (IHC). Then, it was found that this expression was correlated with various clinicopathological parameters including histological grading, hormone receptor (HR) status, and patient survival. Results PCSK9 expression positively correlated with pathohistological grading and hormone receptor status, but negatively with patient survival. GSEA showed low PCSK9 expression groups enriched in immune-related pathways, while high expression groups favored coagulation pathways. CIBERSORT analysis revealed a notable negative association between PCSK9 expression and γδ T cells, suggesting PCSK9’s role in modulating tumor microenvironment (TME) immune reactivity. Low PCSK9 expression was associated with a more favorable response to neoadjuvant therapy in patients. Conclusions PCSK9 expression in HER2-positive BC is a significant prognostic indicator, with higher levels related to worse clinical outcomes. These results suggest PCSK9’s potential utility in predicting treatment responses and guiding therapeutic strategies for HER2-positive BC patients.

Objectives Studies on the impact of hormone replacement therapy (HRT) on hepatocellular carcinoma (HCC) have been investigated in the past. This study aims to further address this topic using a large population dataset of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (NIH, USA). Methods Multivariable logistic regression was used for the analysis of women in the entire PLCO cohort. Results A non-significant reduction in the risk of developing HCC was observed in women using HRT compared to never users (OR=0.61, 95 % CI: 0.21–1.79, p=0.367). Oral contraceptive use was significantly associated with reduced risk of HCC in the HRT group, (OR=0.17, 95 % CI: 0.00–0.82, p=0.028), and there was a nearly-significant interaction between HRT use and oral contraceptive use (p=0.054). Regardless of HRT use, those with pre-existing liver comorbidities of hepatitis or cirrhosis were at the highest risk of developing HCC (OR=5.09, 95 % CI: 1.13–22.81, p=0.034). However, liver comorbidities of hepatitis or cirrhosis and exposure to HRT showed a significant interaction (p=0.0001). Conclusions In those taking HRT, oral contraceptive use was significantly protective against HCC, suggesting that a longer period of hormone use (oral contraceptive plus HRT) provides additional protection against HCC than HRT alone. Overall, the low numbers of HCC diagnoses, which reflect the wider healthy female population, limited our ability to establish statistical significance regarding the impact of HRT on HCC incidence, which requires further prospective studies of larger populations.

A Commentary on Plant-Based and Ketogenic Diets as Diverging Paths to Address Cancer: A Review by Shah AU and Iyengar NM. JAMA Oncol 2022 Aug 1;8(8):1201–8. doi: 10.1001/jamaoncol.2022.1769.

Renal cell carcinoma (RCC) is one of the 10 most common human cancers representing 3–4 % of all malignant diseases, and almost 30 % of cases are diagnosed in an advanced or metastatic stage. Many studies have demonstrated that alterations in cell metabolism are involved in the development of RCC and that many altered genes have a fundamental role in controlling metabolic features in this tumor. Recent reports revealed that metabolic reprogramming is also associated with disease progression. Metastasis, particularly through the formation of a tumor thrombus within the vascular system, is a critical aspect of RCC progression. Recent advancements in understanding genetic and nongenetic variations in tumors have led to a deeper understanding of RCC evolution and intratumor heterogeneity, along with the functional characterization of cellular and molecular components of tumor microenvironment. This commentary briefly explores the novel findings in advanced RCC, highlighting the role of high-throughput technologies and multi-omics approach in the understanding of its pathogenesis and the identification of new therapeutic targets.