Anaplastic thyroid carcinoma (ATC) is the rarest and most aggressive form of thyroid cancer, marked by a poor prognosis and resistance to conventional treatments. Like many malignancies, ATC has a complex genetic landscape, with numerous mutations driving tumor initiation, progression, and therapeutic resistance. However, recent advances in molecular research have expanded our understanding of these genetic alterations, paving the way for new targeted treatment strategies. Currently, therapies targeting specific genetic mutations, such as BRAF and MEK, show promise, but their effectiveness is limited to patients harboring these mutations. To explore broader therapeutic possibilities, we conducted a comprehensive literature review using the PubMed database and Google to identify studies on key genetic mutations in ATC. By leveraging these molecular insights, we aim to highlight potential therapeutic avenues that could enhance treatment options and improve patient outcomes.

Ovarian cancer is the deadliest gynecologic cancer, mainly because it is often diagnosed late and resists standard treatments. The tumor microenvironment (TME) plays a major role in disease progression and therapy failure. Two key components of the TME, cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), create conditions that facilitate tumor growth and immune evasion. CAFs are highly diverse and originate from sources like fibroblasts and stem cells. They support cancer by remodeling the extracellular matrix, promoting angiogenesis, and releasing cytokines and growth factors that aid tumor survival. TAMs, which are usually in an M2 state, also promote metastasis and suppress immune responses by secreting immunosuppressive molecules. Together, CAFs and TAMs interact with cancer cells to activate pathways such as the TGF-β, IL-6, and PI3K/AKT pathways, which drive resistance to therapy. New treatments aim to block these interactions by targeting CAFs and TAMs through depletion, reprogramming, or pathway inhibition, often combined with immunotherapy. Advances such as single-cell sequencing and spatial transcriptomics now enable more precise identification of CAF and TAM subtypes, enabling more targeted therapies. This review summarizes their roles in epithelial ovarian cancer and explores how targeting these cells could improve outcomes.

Anaplastic thyroid carcinoma (ATC) is the rarest and most aggressive form of thyroid cancer, marked by a poor prognosis and resistance to conventional treatments. Like many malignancies, ATC has a complex genetic landscape, with numerous mutations driving tumor initiation, progression, and therapeutic resistance. However, recent advances in molecular research have expanded our understanding of these genetic alterations, paving the way for new targeted treatment strategies. Currently, therapies targeting specific genetic mutations, such as BRAF and MEK, show promise, but their effectiveness is limited to patients harboring these mutations. To explore broader therapeutic possibilities, we conducted a comprehensive literature review using the PubMed database and Google to identify studies on key genetic mutations in ATC. By leveraging these molecular insights, we aim to highlight potential therapeutic avenues that could enhance treatment options and improve patient outcomes.

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer.

High-Grade Serous Ovarian Carcinoma (HGSOC) is a highly heterogeneous disease. Machine learning-based cellular morphometric biomarkers (CMB-ML) have been identified across multiple tumor types, capturing tissue heterogeneity, predicting tumor microenvironments (TME) and clinical outcomes. We aimed to identify ethnicity-specific CMBs in African American and White HGSOC patients using whole-slide images (WSIs) and assess their associations with overall survival (OS). Analysis of 109 patients from The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) cohort was validated in WSIs from 22 patients in the Loma Linda University (LLU) cohort. We linked immune checkpoint markers (ICM) to CMB scores and confirmed via immunohistochemistry. We identified and validated three ethnicity-specific CMBs — 73, 80, and 215 with significant frequency differences. Higher CMB 73 and 80 frequencies correlated with shorter OS in African Americans (p=0.022, p=0.023), while higher CMB 215 frequency was linked to improved OS in White patients (p=0.051). Molecular analysis of TCGA-OV cohort revealed lower immune infiltration in African Americans and higher ICM expression in Whites (PDCD1: p=0.033, PDCD1LG2: p=0.014, CD8A: p=0.014). Immunohistochemistry in the LLU-OV cohort showed expression of predicted markers CD3, CD8, and PDCD1. Although there were no significant differences between the two ethnic groups, CMB-ML explores a new avenue for understanding health disparities.

Background/Objectives: Anaplastic thyroid cancer (ATC) is a rare and highly aggressive thyroid malignancy with limited treatment options. Loss of the sodium/iodide symporter makes ATC resistant to radioactive iodine therapy, highlighting the need for alternative therapeutic targets. This study evaluated L-type amino acid transporter 1 (LAT-1) and vitamin D receptor (VDR) as potential targets in ATC. Methods: We examined LAT-1 (SLC7A5) and VDR gene expression using TCGA data from the UALCAN database. Protein expression was evaluated by immunohistochemistry in 28 formalin-fixed, paraffin-embedded ATC specimens from Loma Linda University Health. We assessed staining intensity and distribution and compared expression between male and female patients. Results: TCGA analysis showed significantly higher SLC7A5 expression in thyroid tumors compared with normal thyroid tissue (*p = 0.0115), while VDR was strongly increased in tumors (**p < 0.001) and across all tumor stages. All 28 ATC specimens expressed both LAT-1 and VDR, although staining intensity and distribution varied among tumors. LAT-1 was primarily localized to the membrane and cytoplasm of tumor cells, with additional expression in stromal and endothelial cells. VDR showed membranous, cytoplasmic, and occasional nuclear expression. LAT-1 expression did not differ significantly by sex (ns, not significant, p = 0.19), whereas VDR expression was significantly higher in females than males (**p = 0.0014). Conclusions: LAT-1 and VDR are broadly expressed in ATC despite substantial intratumoral heterogeneity. Their consistent expression supports further investigation as potential targets for radioligand or other ligand-directed therapies. The higher VDR expression observed in female patients also suggests a potentially important sex-associated difference that warrants validation in larger ATC cohorts.