The global incidence of thyroid cancer (TC) has markedly increased in recent years, making it the most prevalent endocrine‑related cancer worldwide. TC primarily originates from follicular and parafollicular cells of the thyroid gland, and includes four main pathological types: Papillary TC (PTC), follicular TC, medullary TC (MTC) and anaplastic TC. Notably, characteristic oncogenes and tumor suppressor genes are associated with TC, which are considered targets for the development of treatment strategies. The rearranged during transfection (RET) gene serves a pivotal role in the development of TC, and mutations and fusions of this gene are closely associated with the onset of MTC and PTC. The structure of RET includes four cadherin‑like domains and 16 cysteine residues in its extracellular domain, which confer unique functionalities and contribute to its intracellular role. RET activation is a complex process involving multiple intracellular events, including calcium ion binding, glial cell line‑derived neurotrophic factor family ligand binding, and RET receptor aggregation, dimerization and autophosphorylation. The present study reviews the structure and function of the RET proto‑oncogene and its pathogenic roles in various TC subtypes.

RNA polymerase II (Pol II) is an essential eukaryotic enzyme that transcribes protein‑coding genes and various non‑coding RNAs. RNA polymerase II, I and III subunit L (POLR2L) is a highly conserved component shared by RNA polymerase subunits I, II, and III, which contributes to transcriptional regulation, enzymatic structural integrity, key cellular processes such as proliferation, differentiation, and stress responses. Recent research has shown that POLR2L is not merely a Pol II structural subunit but also plays key roles in disease progression, particularly cancer, where POLR2L dysregulation contributes to tumor growth, metastasis, and resistance to chemotherapy. Additionally, POLR2L is closely linked to major signaling pathways including the PI3K‑Akt, Wnt/β‑catenin, and TGF‑β pathways, highlighting the diverse roles played by POLR2L in cellular signaling. This review summarizes current knowledge on the structural and functional properties of POLR2L, its involvement in various diseases, and its potential as a therapeutic target. By outlining the diagnostic and therapeutic relevance of POLR2L, this review aims to provide a framework for understanding how POLR2L related research may inform transcriptional regulation and its impact on human health and disease.

Histone modification is an important mechanism of epigenetic regulation. New histone modifications play key roles in the regulation of gene expression and in the development and progression of various diseases. In addition to histone modifications, epigenetic regulation includes classic pathways such as DNA methylation, chromatin remodeling complexes and non‑coding RNAs, which interact with each other and jointly shape the occurrence and development of gastric cancer (GC). The present study systematically elaborated on the role of histone modification in GC and introduced several main types of histone modification, including acetylation, methylation, citrullination, ubiquitination and lactylation, focusing on histone lactylation modification and exploring its biochemical basis, interaction with other modifications and functions such as metabolic reprogramming, cell proliferation, migration and immune escape, covering non‑tumor and other cancer fields. On this basis, the specific application of histone modification (acetylation, methylation and other modifications) in GC is further explained and the effects of histone lactylation on metabolic reprogramming, proliferation, migration and immune escape of GC are analyzed in detail. Finally, the clinical significance of histone lactylation modifications in the diagnosis and prognosis of GC, biomarkers, therapeutic targets and drug resistance mechanisms provides a reference for an in‑depth understanding of the role of histone modifications, especially lactylation modifications, in the development of GC and clinical transformation applications.

Lung cancer is an aggressive malignancy associated with a rapid progression and poor prognosis, for which immunotherapy only exhibits modest efficacy in most patients. In lung cancer, high lactate is associated with a low immunotherapy response and shortened survival; however, causal lactylation‑related genes remain to be elucidated. In the present study, candidate genes were screened using Mendelian randomization (MR) analysis, with expression quantitative trait loci data and genome‑wide association study summary statistics used as analytical resources. A total of 46 lactylation‑related genes were included in the MR analysis, and multiple testing correction was performed using the false discovery rate (FDR) and Bonferroni methods to control the false‑positive risk. MR identified three core genes [platelet‑type phosphofructokinase; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; and stathmin 1 (STMN1)]. Among these genes, only STMN1 was significantly associated with increased lung cancer risk (inverse variance weighting original P=0.005, FDR‑corrected P=0.014995, Bonferroni‑corrected P=0.014995, odds ratio=1.741, 95% confidence interval: 1.182‑2.564), with robust results confirmed by heterogeneity/pleiotropy/sensitivity analyses. Subsequently, transcriptomic analysis was conducted to assess STMN1 expression in lung cancer tissues and its association with patient survival. In vitro (cell proliferation, migration, invasion and apoptosis assays) and in vivo experiments (murine tumor models) were also conducted to explore the function of STMN1. STMN1 exhibited upregulation in lung cancer tissues, and was associated with a shorter survival, reduced antitumor immune cell infiltration and an immunosuppressive tumor microenvironment (TME) phenotype. STMN1 knockdown inhibited lung cancer malignancy both in vitro and in vivo, and modulated key markers, whereas its overexpression exhibited the opposite effects. Additionally, STMN1 promoted global histone lactylation and histone H3 lysine 18 lactylation in lung cancer cells, establishing a direct functional link between STMN1 and the lactylation pathway. In conclusion, STMN1 is a lactylation‑related causal oncogene in lung cancer, driving progression via malignant phenotypes, and its high expression is associated with an immunosuppressive TME that may synergistically facilitate tumor progression. Therefore, STMN1 may be considered a novel target for lung cancer therapy.

Bladder cancer (BCa) progression is closely linked to the immune microenvironment. However, the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood. This study aims to identify a key molecule and elucidate its mechanisms, providing a theoretical basis for identifying novel therapeutic targets.

ADP-ribosyltransferases (ARTs) regulate key processes in cancer, including DNA repair, transcription, immune responses, and treatment resistance. The clostridial toxin-like ADP-ribosyltransferase (ARTC) family and the diphtheria toxin-like ADP-ribosyltransferase (ARTD) family play a crucial role in genomic stability by modification of proteins either with mono(ADP-ribosyl)ation (MARylation) or poly(ADP-ribosyl)ation (PARylation). These ARTs are promising therapeutic targets and could serve as biomarkers in cancer management. This review explores the roles of these enzymes and current knowledge on specific inhibitors. A literature search was conducted in PubMed and Google Scholar to identify studies published between 1992 and 2025 on ADP-ribosyltransferases and their roles in cancer. Among ARTC family, ART1 and ART3 modulate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, influencing angiogenesis, tumor growth, and immune evasion via cluster of differentiation 8+ (CD8+) T-cell apoptosis. Within the ARTD family, poly(ADP-ribose)polymerase (PARP)1 and PARP2 are activated by DNA single-strand breaks and are clinically validated targets in cancers with homologous recombination deficiency, such as breast cancer susceptibility genes 1/2 (BRCA1/2)-mutated breast cancer. Their inhibition exemplifies synthetic lethality and has shown clinical efficacy. Four PARP inhibitors, olaparib, niraparib, rucaparib, are approved by the Food and Drug Administration (FDA) approved. Despite these advances, selective inhibitors for ARTs remain underexplored. Ongoing research focuses on overcoming PARP inhibitor resistance, improving biomarker-driven patient selection, and expanding therapeutic strategies that target ART-related pathways.

Long non-coding RNAs have been found to play a pivotal role in breast cancer, yet the majority of these lncRNAs remain to be thoroughly investigated. This study aimed to explore the role of differentially expressed long non-coding RNAs (lncRNAs) in breast cancer stemness and drug sensitivity.

Lung adenocarcinoma (LUAD), the most prevalent histological subtype of lung cancer, remains a leading cause of cancer-related mortality due to late diagnosis, metastasis, and therapy resistance. The aim of the study is to investigate the role of Kinetochore Scaffold 1 (KNL1) in promoting LUAD progression and its underlying molecular regulatory mechanisms.

Tumor recurrence is a major determinant of poor prognosis in hepatocellular carcinoma (HCC), yet its cellular and molecular basis remains incompletely understood. This study aimed to identify recurrence-associated genes at single-cell resolution and to develop a prognostic model for predicting survival outcomes and immunotherapy responsiveness in HCC.

Hepatocellular carcinoma (HCC) has limited systemic options with substantial toxicity. G-quadruplex (G4) structures in oncogene promoters are attractive but challenging drug targets. This study aimed to determine whether glutamic acid-chelated cobalt (GACC) is a G4-active scaffold with anti-HCC efficacy and favorable in vivo safety, and whether an AI-guided phenotypic response surface (PRS) can optimize less toxic combinations.

-Synovial sarcoma is a rare soft tissue sarcoma. Treatment of synovial sarcoma includes surgery, radiation, pazopanib, and chemotherapy. Targeted therapies, such as B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitors, are emerging as a potential treatment option. We describe the sixth case of a BRAFV600E synovial sarcoma, the first extra-thoracic case. This case is the first to show a complete pathological response to BRAF & mitogen-activated protein kinase kinase (MEK) inhibitors.

Progesterone (P4) is believed to inhibit breast cancer growth, but its role in counteracting estrogen (E2)-driven progression remains unclear. This study aimed to investigate the inhibitory effect of P4 on E2-induced cell proliferation, migration, and invasion in Estrogen receptor (ER)+/progesterone receptor (PR)+ breast cancer cells by examining its regulatory role in the epithelial-mesenchymal transition (EMT).

Breast cancer metastasis remains the leading cause of mortality and frequently targets the bone. Breast cancer cells release soluble factors and extracellular vesicles that disrupt bone marrow (BM)/bone homeostasis, promoting osteoclastogenesis and the accumulation of senescent cells. In line with updated cancer hallmarks, senescent mesenchymal stem/ stromal cells (MSCs), osteoblasts, and osteocytes contribute to remodeling of the BM microenvironment, thereby favoring pre-metastatic niche (PMN) formation and subsequent bone metastasis. We previously demonstrated that untreated stage III-B breast cancer patients (BCPs) exhibit increased oxidative stress and elevated reactive oxygen species (ROS) levels, accompanied by senescent and functionally impaired BM-MSCs-key regulators of BM/bone homeostasis. In the present study, we sought to identify the molecular targets affected by oxidative stress that drive MSC senescence in these patients.

Malignant melanoma (MM) is a highly aggressive skin cancer known for its rapid progression, potential for metastasis, and resistance to treatment. Despite advances in targeted therapies and immunotherapy, the prognosis for metastatic melanoma remains unfavorable. Recent research has shed light on the significance of epigenetic modifications in the pathogenesis of melanoma, revealing critical mechanisms of melanoma development and progression. Epigenetic modifications, including DNA and RNA modifications, histone modifications, chromatin remodeling, and non-coding RNA regulation, disrupt normal gene expression without modifying the DNA sequence, leading to cellular transformation, invasion, immune evasion, and therapeutic resistance. The reversible nature of epigenetic modifications opens up new opportunities for melanoma recognition and classification, as well as therapeutic applications, including the development of diagnostic and prognostic biomarkers and innovative targeted therapies aimed at restoring normal gene function and enhancing the efficacy of existing treatments. This review will focus on the multifaceted role of epigenetic dysregulation in melanoma. The future integration of epigenetic data and genomic profiling with clinical outcomes, likely facilitated by artificial intelligence (AI) algorithms, holds promise for personalized treatment strategies that are informed by precise and combinatorial diagnostic tools, ultimately improving melanoma care. The study aims to deliver a comprehensive overview of the current state of epigenetics in melanoma.

MicroRNAs (miRNAs) are small, non-coding RNAs that play a key role in the development of chemoresistance in various cancer types, including colorectal cancer (CRC). In this study, we aimed to study the underlying mechanisms of miRNA in chemotherapy-resistant CRC.

After about 20 years of exciting improvements in treatment efficacy outcomes of advanced epidermal growth factor receptor (EGFR) mutant and anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC), also combined with a progressively better safety profile, from chemotherapy to new generation tyrosine kinase inhibitors (TKIs) (osimertinib, alectinib, brigatinib), the recent MARIPOSA and CROWN trials have changed this trend. For the first time in the history of EGFR and ALK treatments, we must face the issue of being a step behind in terms of toxicity profile. The combination of amivantamab plus lazertinib in EGFR mutant NSCLC, and lorlatinib in ALK rearranged NSCLC, has improved efficacy outcomes as never before. The story would be easy and totally positive if these two innovative, amazing treatments were not associated with new peculiar features in safety profiles that must be discussed with patients, because they potentially affect their quality of life. When treating these patient populations, the peculiar safety profiles of amivantamab plu lazertinib and lorlatinib require a well-structured shared decision making, "where and when", both the high probability of a longer survival and the risk of worse quality of life must be well announced and explained to our patients before the shared final treatment choice.

Cholecystokinin A receptor (CCKAR) has been linked to poor prognosis in colon cancer patients, but the role of CCKAR in colon cancer cell invasiveness and the underlying mechanisms remain elusive. This study aimed to explore the effect of CCKAR on the invasive potential of colon cancer cells.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with high recurrence rates. Lymphovascular invasion (LVI) predicts a poor prognosis, yet its molecular drivers remain unclear. BOC cell adhesion-associated, oncogene-regulated (BOC, also known as Brother of CDO [Cell adhesion molecule-Related/Down-regulated by Oncogenes]), a hedgehog-related cell surface receptor, may serve as a biomarker for tumor progression and chemotherapy response. The study aimed to investigate the role of BOC in UTUC and its potential to predict LVI and chemotherapy response.

Piwi-associated RNAs are small non-coding RNAs implicated in cancer, yet few have been characterized in colorectal cancer (CRC). This study aimed to identify a CRC-related piRNA and investigate its clinical relevance, biological function, and biomarker potential.

Lactate, as a critical byproduct of tumor metabolic reprogramming, plays an important role in DNA damage repair and tumor immune infiltration. This work aims to elucidate the molecular mechanisms by which lactate promotes tumor DNA damage repair (DDR) and subsequent immune evasion.