Thyroid cancer is the most widespread endocrine malignancy. Of all the cases of thyroid cancer, approximately 95% arise from follicular cells. Familial non-medullary thyroid cancers constitute 3-9% of all the reported cases of thyroid cancer and are diagnosed by the presence of two or more first-degree relatives with cancer. Most familial cases of non-medullary thyroid cancer are caused by papillary thyroid cancer and its histological variants. Although some genes predisposing to familial papillary thyroid cancer have been identified, their functionality is unclear, and routine examination is not recommended. Some of these cases may be syndromic, but most cases (>95%) are non-syndromic. Various researchers have suggested an association between familial papillary thyroid cancers and earlier age of onset, higher multifocal tumor rate, extrathyroid enlargement, lymph node metastasis, and disease recurrence. Therefore, screening and close follow-up of other family members are essential when familial papillary cancer is diagnosed. This case report presents a familial papillary thyroid cancer series involving an index male patient with a breast cancer history and his three sisters with thyroid papillary cancer.

Introuduction: FAT atypical cadherin 1 (FAT1), the Hippo pathway and Yes-associated protein (YAP) signaling play significant roles in cell proliferation, differentiation, and apoptosis. Dysregulation of these pathways contributes to tumorigenesis in multiple cancers, including head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), and breast cancer.

Premenopausal women carrying a BRCA1 or BRCA2 mutation are frequently advised to undergo risk-reducing bilateral salpingo-oophorectomy (BSO) to lower their significantly increased lifetime risk of ovarian cancer. However, this procedure induces abrupt estrogen deprivation, resulting in premature menopause with well-documented consequences including vasomotor symptoms (e.g., hot flashes, night sweats), urogenital atrophy, and long-term risks such as osteoporosis, cardiovascular disease, and cognitive decline (Nelson in Lancet 371(9614):760-770, 2008; Shuster et al. in Maturitas 65(2):161-166, 2010). To alleviate symptoms and prevent sequelae, hormone replacement therapy (HRT) remains the most effective intervention. However, the issue becomes complex when the patient has a personal history of triple-negative breast cancer (TNBC). Although TNBC lacks hormone receptor expression, systemic HRT has traditionally been contraindicated in breast cancer survivors, as early studies indicated an increased risk of recurrence with hormone therapy, even in receptor-negative subtypes (Kenemans et al. Lancet Oncol 10(2):135-146, 2009a). This leads to a critical question: Is HRT appropriate in BRCA mutation carriers with a history of TNBC following BSO, and if so, under what clinical conditions? What do current international guidelines, evidence, and expert recommendations suggest?

Clonal haematopoiesis (CH) is an age-related condition increasingly recognised for its relevance in haematologic malignancies. In chronic lymphocytic leukaemia (CLL), its prevalence and clinical implications are gaining attention, particularly in the context of prolonged patient survival and the widespread adoption of targeted therapies. A comprehensive understanding of the biological and clinical significance of CH in CLL is therefore essential.

The aryl hydrocarbon receptor (AhR) is a ubiquitously expressed, ligand-activated transcription factor which has been extensively studied for its role in mediating the toxic effects of several common environmental pollutants. However, more recent findings associating AhR with carcinogenesis and tumor progression have expanded the scope of AhR research and established the preclinical significance of AhR as a possible target for cancer therapy. In this review, the current knowledge of the role of AhR in cancer will be discussed, and evidence from an array of experimental cancer and immune models will be presented. It has been observed that AhR potentiates oncogenic mutations through induction of genetic damage and transactivates EGFR to promote proproliferative signaling along the classical Ras/Raf/MAPK and PI3K/Akt pathways. Furthermore, AhR downregulates E-cadherin via multiple axes to facilitate epithelial-to-mesenchymal transition and contributes to a shift of the tumor immune microenvironment to a predominantly regulatory milieu. The sheer versatility of AhR as a protumor factor should provide sufficient grounds for further investigation of the persisting question of whether targeting AhR can disrupt tumor progression in vivo.

The incidence and mortality of colorectal cancer (CRC) are steadily rising. Phosphatase-Tensin Homolog Deleted on Chromosome 10 (PTEN) expression is often dysregulated during tumourigenesis; however, its prognostic value in CRC remains debated. This study evaluated the correlation between PTEN expression and the clinicopathological characteristics of CRC patients, and its prognostic significance. A systematic literature review was conducted across Web of Science, PubMed, Cochrane Library, and CNKI up to June 2023. Thirteen studies with a total of 2,377 participants were included. PTEN expression was significantly lower in CRC tissues than in normal mucosa tissues. Positive PTEN expression was associated with better overall survival and favourable pathological features. No significant correlation was found with age, gender, differentiation grade, tumour size, or distant metastasis. Negative PTEN expression is a poor prognostic marker in CRC and may serve as a potential indicator for disease monitoring and outcome prediction. Key Words: PTEN, Colorectal cancer, Prognosis, Meta-analysis, Clinical characteristics.

Cervical cancer is caused by persistent infection with high-risk human papillomaviruses (HR-HPV). Current screening programs rely on cytology and HR-HPV molecular detection. However, as most infections are transient, effective triage for HR-HPV positive women is crucial to identify those at high risk of progression to cancer. DNA methylation analysis, an epigenetic modification involved in HPV-induced oncogenesis, is emerging as a promising triage tool. This marker could stratify risk, thereby reducing invasive examinations (colposcopies) and unnecessary overtreatment (conizations), which may impact future pregnancies. Methylation tests, applicable to both cervical smears and self-collected vaginal samples, target viral genes (e.g., L1, L2) or host cell genes (e.g., FAM19A4, CADM1, MAL). While many markers show good performance, their optimal place in screening strategies and the choice of the most relevant test are still under investigation and require further comparative studies.

Locoregional failure remains a major barrier to cure in head and neck squamous cell carcinoma (HNSCC). Radiotherapy dosing remains largely dictated by anatomy, despite clear biological determinants of radiosensitivity. This review synthesises recent clinical and molecular evidence defining radioresistance and the emerging tools to guide more personalised radiotherapy.

Human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) remains a challenging disease with poor prognosis. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker to improve risk stratification, detect minimal residual disease (MRD), and guide treatment adaptation. This review synthesizes recent advances in ctDNA technologies and their clinical relevance for HPV-negative HNSCC.

Triple negative breast cancer (TNBC) is an aggressive BC subtype with limited therapeutic options and poor clinical outcomes. This subtype accounts for 15‑20% of all BC cases and contributes to nearly 40% of BC mortalities. The chemokine C‑X‑C motif ligand 1 (CXCL1) is a key player in TNBC progression through several signaling pathways, including NF‑κB, MAPK and related cascades. CXCL1 contributes to tumor growth, metastasis, immune modulation and resistance to therapy, however its role and therapeutic potential in TNBC has not been comprehensively described. The present review aimed to summarize CXCL1 biology in TNBC, with a focus on its prognostic relevance, role in the tumor microenvironment and potential as a therapeutic target, as well as emerging strategies aimed at modulating CXCL1 signaling. However, challenges remain in translating these findings into clinical application, including incomplete understanding of certain molecular mechanisms underlying CXCL1 function, unclear prognostic value, the need for validation of potential inhibitors in large and diverse cohorts and the lack of well‑designed clinical trials testing CXCL1‑targeted approaches. Addressing these challenges through rigorous preclinical work and carefully designed clinical trials is key to define the true therapeutic potential of CXCL1 in TNBC to advance precision medicine strategies and enhance clinical outcomes in patients with TNBC.

Claudin‑7 (CLDN7) is a key component of epithelial tight junctions. It plays a vital role in maintaining cell polarity, barrier integrity and paracellular transport. Abnormal CLDN7 expression is closely related to the onset and progression of various diseases. It is especially markedly associated with the growth and metastasis of multiple cancers. Additionally, dysregulated CLDN7 expression contributes to the progression of intestinal, skin and respiratory system diseases. The present review summarized the structure, expression, physiological functions, stability and regulatory mechanisms of CLDN7, emphasizing its role in tumors. The expression patterns, regulatory mechanisms, effect on malignant phenotypes and clinical significance of CLDN7 were also discussed.

Remaining challenges in management of patients with germ cell tumors (GCTs) include selecting the optimal treatment modality in patients with early metastatic disease, biomarker development and developing newer treatments in patients with refractory disease. This review aims to highlight recent developments in these domains.

PARP inhibitors (PARPi) have rapidly reshaped the treatment landscape for metastatic prostate cancer, moving from biomarker-selected monotherapy in metastatic castration-resistant prostate cancer (mCRPC) to first-line combination strategies with androgen receptor pathway inhibitors (ARPIs) and more recently, into metastatic hormone-sensitive disease (mHSPC). This review summarizes the evidence-based use of PARPi in metastatic prostate cancer, integrating the mechanistic rationale and guideline perspectives. We also highlight the resistance mechanisms that inform patient selection and underpin emerging strategies.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a dismal 5‑year survival rate of ~9%, primarily due to late diagnosis, aggressive metastasis and profound resistance to conventional therapies. Epithelial‑mesenchymal transition (EMT) has been identified as a pivotal driver of these malignant phenotypes, facilitating early invasion, dissemination and treatment failure. The present review systematically elaborated on the multidimensional mechanisms underlying EMT in PDAC, emphasizing its operation as a spectrum of hybrid epithelial/mesenchymal states rather than a binary switch. Key molecular mechanisms include the activation of core transcription factors (such as Snail, ZEB, Twist), intricate crosstalk within the tumor microenvironment (such as transforming growth factor-β and hepatocyte growth factor signaling from stromal cells) and dynamic epigenetic reprogramming. Furthermore, EMT critically contributes to the acquisition of cancer stem cell properties and enhances the survival and colonization of circulating tumor cells. The present review also outlined emerging translational strategies targeting EMT‑related pathways, highlighting agents such as STNM01 that have entered early-phase clinical trials. By synthesizing unprecedented insights into EMT's plastic spectrum states and subtype‑specific regulatory networks, this work establishes a paradigm‑shifting framework for advancing EMT‑targeted therapies; offering transformative potential to overcome PDAC's historical therapeutic barriers and substantially improve patient survival outcomes. By synthesizing current insights from molecular pathways to therapeutic applications, the present review confirmed EMT as a promising therapeutic target and provides a strategic framework for advancing PDAC treatment, with the ultimate goal of improving clinical outcomes.

Colorectal cancer (CRC) remains a major global health concern, with a rising incidence among younger adults and persistently high mortality in advanced stages, despite significant scientific and technological progress. Its etiology is multifactorial, involving lifestyle factors, genetic susceptibility, chronic inflammation, and gut microbiome dysbiosis. Recent advances in screening, molecular profiling, surgery, and systemic therapies have substantially reshaped CRC management. This narrative review was conducted through a comprehensive literature search of PubMed/MEDLINE, Scopus, and Web of Science databases, covering publications from January 2015 to June 2025. Peer-reviewed articles addressing CRC epidemiology, molecular pathways, screening and diagnostic strategies, surgical management, systemic therapies, and emerging treatment modalities were selected. Evidence was qualitatively synthesized and organized into clinically relevant thematic domains. Recent progress in CRC screening, including advanced endoscopic imaging, fecal DNA testing, and blood-based biomarkers, has improved early detection, although implementation remains uneven. Molecular characterization such as MSI-H/dMMR status, RAS/RAF mutations, HER2 amplification, and consensus molecular subtypes â?" guides prognostic assessment and personalized therapy. Surgical resection remains the cornerstone of curative-intent treatment, with minimally invasive and robotic approaches reducing morbidity while maintaining oncologic safety. Techniques such as complete mesocolic excision and total mesorectal excision, along with multimodal strategies for advanced disease, have expanded therapeutic options. Despite these advances, challenges persist, including therapeutic resistance, tumor heterogeneity, limited immunotherapy efficacy in microsatellite-stable disease, and rising early-onset CRC. Future progress relies on precision medicine, ctDNA-guided monitoring, microbiome-targeted strategies, and optimized surgical selection.

IL‑6, a pleiotropic inflammatory cytokine predominantly secreted by fibroblasts, myeloid‑derived suppressor cells, tumor‑associated macrophages and tumor cells, is associated with poor prognosis of and therapeutic resistance in non‑small cell lung cancer (NSCLC). The activation of signaling pathways, including the JAK/STAT3, MAPK and PI3K/AKT pathways, promotes tumor survival. Furthermore, the IL‑6/JAK/STAT3 signaling axis has emerged as a key driver of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKI) resistance, orchestrating intricate crosstalk within the tumor microenvironment (TME) to promote cell survival and immunosuppression. The present review synthesized current evidence on the dual role of IL‑6 in mediating EGFR‑TKI resistance and blunting anti‑tumor immunity. The present review highlights the preclinical rationale for combining IL‑6 blockade with EGFR‑TKI or immune checkpoint inhibitors to overcome refractory disease. The present review also highlights the structure, molecular mechanisms and clinical insights of IL‑6 in the TME of EGFR‑mutant NSCLC and may provide optimized therapeutic strategies for EGFR‑TKI‑refractory NSCLC.

Diffuse large B‑cell lymphoma (DLBCL), the most prevalent subtype of lymphoma, is characterized by rapid growth and a poor prognosis, with the R‑CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) being the standard first‑line therapy. However, 30‑40% of patients experience early relapse or refractoriness to treatment, highlighting the need to understand the mechanisms of chemoresistance. The present review synthesizes the current knowledge on the molecular mechanisms underlying chemoresistance in DLBCL, including genetic mutations, epigenetic modifications, aberrant activation of signaling pathways, alterations in drug metabolism and efflux, and upregulation of anti‑apoptotic proteins. In addition, the role of the tumor microenvironment in mediating therapeutic resistance is discussed and biomarkers associated with chemoresistance are explored. Furthermore, novel therapeutic strategies targeting chemoresistance, such as immunotherapy, metabolic modulators and epigenetic therapies, are examined. Understanding these mechanisms is crucial for developing effective treatment strategies to overcome resistance and improve patient outcomes in DLBCL.

The present review focuses on the molecular functions of prostate‑specific membrane antigen (PSMA) as a biologically active protein. Its clinical use as a positron emission tomography imaging marker or radioligand therapy target is beyond the scope of the current review. The role of PSMA (also known as folate hydrolase 1/glutamate carboxypeptidase II/N‑acetylated‑α‑linked acidic dipeptidase) has progressed from that of a prostate cancer biomarker to a functional driver of tumor biology. Structurally, PSMA is a type II transmembrane glycoprotein with glutamate carboxypeptidase and folate hydrolase activities, linking glutamate and one‑carbon metabolism to proliferation, redox balance and epigenetic regulation. PSMA undergoes clathrin‑dependent endocytosis and interacts with various scaffolding proteins, such as filamin A and receptor for activated C kinase 1, which are properties that underlie its functional role as a molecular signaling hub, in addition to being a therapeutic entry point. Its expression is dynamically regulated by androgen receptor signaling, NF‑κB activation and epigenetic modifiers, contributing to intra‑patient heterogeneity and treatment resistance. PSMA expression is not restricted to prostate epithelium but is also expressed in tumor‑associated endothelium across multiple malignancies, where it can promote angiogenesis through integrin/PI3K‑AKT‑mTOR signaling and paracrine induction by extracellular vesicles. These molecular functions can result in immune exclusion, stromal activation and neuronal interactions, positioning PSMA as a key regulator of the tumor microenvironment. Although PSMA‑targeted imaging and therapies have demonstrated substantial clinical utility, understanding the biological basis of the function of PSMA is essential for interpreting the heterogeneous clinical responses and for designing next‑generation therapeutic strategies in association with this protein. By integrating enzymatic activity, non‑enzymatic scaffold signaling and tumor microenvironmental regulatory information, the present review provides a functional framework in the PSMA biology field and discusses how these molecular properties can be leveraged to develop novel rational and effective PSMA‑targeted interventions.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Despite major advances in therapy, the treatment of ALL remains a significant challenge. Therapeutic protocols are based on the use of combinations of chemotherapeutic drugs. While such combinations increase treatment efficacy, they also complicate the assessment of toxicity. It should be noted that the variability in the occurrence of toxic responses to ALL therapy in children may be determined by the presence of gene variants that influence both the pharmacokinetics and pharmacodynamics of chemotherapeutic drugs. This review summarized and analyzed the most significant and well-studied pharmacogenetic markers to date associated with the toxicity and response to chemotherapeutic agents used in the treatment of pediatric ALL. In particular, pharmacogenetic markers for the following drugs were analyzed: anthracyclines (doxorubicin, daunorubicin), vincristine, glucocorticoids (prednisone, dexamethasone), L-asparaginase, methotrexate, alkylating agents (cyclophosphamide, ifosfamide), 6-mercaptopurine, cytarabine, and etoposide. At present, only a few genes, TPMT and NUDT15, have well-established clinical utility, whereas the clinical relevance of pharmacogenetic markers for other drugs used in pediatric ALL therapy remains under investigation. The review also highlights the main knowledge gaps in current research and outlines promising directions for future studies aimed at integrating pharmacogenetic testing into clinical practice for personalized treatment of ALL.