Cancers最新文献

Background/objective: To comprehensively characterize the genetic landscape of medullary thyroid carcinoma (MTC) in a Romanian cohort.

Methods: Germline and somatic RET testing were performed in 164 MTC patients (105 sporadic, 59 hereditary) consecutively enrolled at a single tertiary center (2021-2024) using genomic DNA or DNA extracted from fresh surgical or paraffin-embedded pathology specimens.

Results: Hereditary MTC (hMTC) accounted for 59/164 (35.9%) cases. Among hMTC, 58/59 (98.3%) had MEN2 (72.4% classic, 5.2% with cutaneous lichen amyloidosis, 5.2% with Hirschsprung disease, and 17.2% with familial medullary thyroid carcinoma), and 1/59 (1.7%) had MEN3. Codon 634 mutations were the most prevalent (33/59, 55.9%). Extracellular cysteine-rich domain mutations were significantly more prevalent in syndromic cases (p = 0.006), while non-cysteine mutations were predominant in apparently sporadic cases (p = 0.006). In advanced MTC (stage III/IV or metastatic), the somatic M918T mutation was the most common (15/20, 75% cases).

Conclusions: Germline RET screening is mandatory for all MTC cases. Somatic testing is critical in advanced disease, where M918T prevails in 75% of cases and guides tyrosine kinase inhibitor therapy. Codon 634 is the most frequent mutation in Romanian MTC, highlighting regional variation warranting population-adjusted screening and earlier prophylactic thyroidectomy.

Background: Globally, the incidence rate of hepatocellular carcinoma (HCC) has increased among elderly patients. Elderly patients often present with multiple comorbidities that affect treatment tolerance and outcomes, and the optimal management strategy for this population has not yet been established. Therefore, we assessed comorbidities in elderly patients and investigated the treatment outcomes of radiotherapy (RT) to liver-confined HCC. Methods: We retrospectively reviewed 40 elderly patients aged ≥70 years with liver-confined HCC, who were treated with RT between 2015 and 2023. Comorbidity was assessed by using the Charlson Comorbidity Index (CCI). Survival outcomes were analyzed using the Kaplan-Meier method. Results: The median age was 75 years (range, 70-87 years). The Barcelona Clinic Liver Cancer stage was 0 in 7 patients, A in 10 patients, B in 9 patients, and C in 14 patients. Most patients (85%) had Child-Pugh class A hepatic function before RT. The CCI scores ranged from 2 to 9 (median, 5). Various RT techniques were applied according to patients' condition, tumor burden, and treatment aim: three-dimensional conformal radiotherapy in four patients, intensity-modulated radiotherapy in 20 patients; and stereotactic body radiotherapy in 16 patients. RT was delivered with radical intent in 30 patients and with palliative intent in 10 patients. The median biological effective dose calculated with an α/β ratio of 10 was 53.7 Gy₁₀ (range, 39-134.4 Gy₁₀). The median follow-up period after RT was 18 months. The 1-year local progression-free survival and overall survival (OS) rates were 74% and 81%, respectively, and the 3-year rates were 44% and 52%, respectively. Patients with CCI < 5 had more favorable OS than those with CCI ≥ 5, but the difference was not statistically significant. Conclusions: RT for liver-confined HCC appears to be a feasible treatment option for elderly patients with multiple comorbidities.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor long-term survival despite advances in surgical techniques, systemic therapies, and perioperative management. High rates of systemic recurrence following curative-intent resection suggest that many patients harbor minimal residual disease (MRD), microscopic tumor burden that persists postoperatively and remains undetectable by conventional diagnostic tools. Recent advances in liquid biopsy technologies, particularly circulating tumor DNA (ctDNA) analysis, alongside detailed characterization of the PDAC mutational landscape, offer a promising non-invasive approach for MRD detection. Emerging evidence indicates that MRD status can serve as a sensitive prognostic biomarker, identify patients at high risk of relapse, and guide personalized perioperative therapy, including optimization of adjuvant treatment. This review summarizes current knowledge on the biology and detection of MRD in PDAC, its implications for perioperative risk stratification and treatment decision-making, and discusses future directions for integrating MRD assessment into clinical practice to enable more precise, individualized patient management.

Background/Objectives: Colorectal cancer (CRC) is a major contributor to cancer-related deaths worldwide. While existing screening tools are effective, their high cost and limited availability restrict widespread adoption, particularly in low- and middle-income settings. The identification of affordable, non-invasive biomarkers is therefore critical to improve early CRC detection and survival outcomes. Methods: A systematic literature search was performed through PubMed, ScienceDirect, Medline, ISI Web of Knowledge, and Google Scholar to identify studies reporting stool- and blood-based biomarkers for CRC detection. Data were extracted using a standardized template, including study details, specimen type, detection method, and diagnostic performance parameters such as sensitivity and specificity. Results: DNA methylation biomarkers demonstrated high diagnostic potential. Syndecan 2 (SDC2) and Short Stature Homeobox 2 (SHOX2) achieved a combined stool sensitivity of 91.35%. Other methylation markers, including NDRG4, SEPT9, and BCAT1, showed a composite sensitivity of 82.7%. Plasma-based methylation markers such as GATA5, FOXE1, and SYNE1 reported sensitivities ranging from 18-47% and specificities of 93-99%. Hypermethylation of SFRP2 and WIF-1 achieved 81.3% sensitivity in CRC and precursor lesions. Matrix metalloproteinases (MMP-2 and MMP-9) were elevated in CRC patients, with stool MMP-9 yielding 72.2% sensitivity and 95% specificity. A stool gene panel (UBE2N, IMPDH1, DYNC1LI1, HRASLS2) reached 96.6% sensitivity and 89.7% specificity, while a methylation-based panel (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, VIM) achieved 90.7% sensitivity. MicroRNAs (miR-21, miR-92a, miR-223, miR-182) showed excellent diagnostic performance, with sensitivities exceeding 96% and specificities above 75%. Conclusions: DNA methylation and microRNA biomarkers hold strong promises for non-invasive CRC screening. Multi-marker panels demonstrate superior diagnostic accuracy and may provide a cost-effective, scalable approach for early CRC detection in resource-limited settings.

(1) Background: Globe-sparing radiotherapy is widely utilised in the treatment of uveal melanoma, but often results in complications requiring vitreoretinal intervention. The outcomes of secondary vitrectomy remain unclear. A multidisciplinary approach involving vitreoretinal and ocular oncology specialists is essential to managing complications. (2) Methods: We reviewed 1794 patients treated with radiotherapy for uveal melanoma between 2012 and 2022. In total, 70 patients underwent secondary vitrectomy after primary radiotherapy treatment. The outcomes included overall tumour control and visual outcome. (3) Results: Complications requiring vitrectomy were more common after proton-beam radiotherapy than plaque brachytherapy (5.4% versus 3.0%). Common indications included vitreous haemorrhage (39%) and retinal detachment/toxic tumour syndrome (31%). The affected tumours were larger, more often ciliary body in origin, and associated with a worse prognosis. Vitrectomy patients had higher rates of enucleation (9% versus 3%), metastasis (16% versus 6%), and visual decline (average 0.60 LogMAR), with limited visual improvement (≥3-line gain in 13%). Proton-beam patients had worse outcomes than plaque brachytherapy patients. (4) Conclusions: Vitreoretinal complications after uveal melanoma radiotherapy are rare, but timely treatment by those with experience may enable patients to keep their eye in situations where enucleation would be the only alternative. Patients and clinicians must understand the risks of complications to make informed decisions about treatment plans, with vitreoretinal surgeons and ocular oncologists key to outcomes.

Background: In this study, 28 caffeic acid phenethyl ester (CAPE) derivatives were designed and synthesized, and their anti-proliferative activities were evaluated against two representative human hepatocellular carcinoma (HCC) cell lines. The half-maximal inhibitory concentration (IC₅₀) was used as the activity metric. Among these derivatives, compound WX006 displayed the most potent anti-proliferative effect, with IC₅₀ values of 3.332 μM and 3.764 μM after 48 h of treatment, significantly lower than those of the parent compound CAPE. Consequently, WX006 was selected for further investigation into its antitumor efficacy and underlying mechanisms.

Methods: To investigate the pharmacological mechanism of WX006, we employed a combination of high-throughput transcriptomics, metabolomics, and mitochondrial function analysis to elucidate its intracellular mechanisms of action.

Results: WX006 disrupts cytoplasmic-mitochondrial metal ion homeostasis, triggering ferroptosis and cuproptosis through iron-copper dysregulation. Computational modeling revealed that WX006 selectively inhibits mitochondrial NDUFS2 subunit of respiratory chain complex I, which may induce NAD⁺ exhaustion and consequent energy metabolism collapse in tumor cells. These "metabolism & metal homeostasis" dual mechanisms collectively underpin its robust anti-tumor effects. Therapeutic efficacy of WX006 was further validated in murine H22 ectopic xenograft and Hepa1-6-Luc orthotopic xenograft models, where WX006 exhibited superior tumor suppression compared to sorafenib, alongside favorable safety profiles.

Conclusions: Our findings establish a foundational rationale for further pharmaceutical development of CAPE derivates as a promising therapeutic candidate for hepatocellular carcinoma.

Background: Prostate cancer (PrCa) outcomes are inferior in regional and rural areas compared to metropolitan centres. We evaluated patterns of care in PrCa patients treated in public and private healthcare facilities in regional Tasmania. Methods: This retrospective study used clinicopathological data for 2180 PrCa patients diagnosed between 2015-2022. Descriptive statistics and regression analyses determined associations between treatment facility (public vs. private) and diagnostic and treatment factors. Results: A significantly greater proportion of public patients were from outer regional/remote areas (prevalence ratio (PR) = 1.25, 95% CI: 1.19-1.31), presented with higher-risk disease (PR = 1.56, 95% CI: 1.22-2.00) and underwent active treatment compared to private patients (PR = 1.07, 95% CI: 1.03-1.11). Men treated privately were most likely to have low-risk PrCa (p < 0.001) and be managed with active surveillance (AS, 52.9%). When stratified by disease risk, public patients with intermediate (p < 0.001) or very high-risk/metastatic disease (p = 0.003) were still significantly more likely to receive active treatment than private patients. Furthermore, except for very high-risk/metastatic patients, public patients took significantly longer to commence treatment, ranging between a mean difference of 40 to 59 days depending on risk category. Conclusions: In Tasmania, treatment pathways for PrCa patients differ significantly between public and private healthcare sectors and may contribute to poorer outcomes in regional and remote areas.

Background: Management of lateral pelvic lymph node (LPLN) metastasis in advanced lower rectal cancer has historically exemplified a fundamental East-West divide. In Japan, the Japanese Society for Cancer of the Colon and Rectum (JSCCR) considers LPLN metastasis a regional manifestation requiring lateral pelvic lymph node dissection (LPLND). In contrast, Western practice has long approached LPLN disease as systemic, prioritizing neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) without additional lateral clearance. Recent Advances: Evidence generated from the JCOG0212 trial and subsequent multicenter cohorts has firmly demonstrated that LPLND markedly reduces lateral local recurrence, particularly in patients with radiologically enlarged nodes. These findings have contributed to a paradigm shift: the 2025 European Society for Medical Oncology (ESMO) Guidelines now endorse selective LPLND for suspicious nodes following neoadjuvant therapy, indicating an emerging convergence between Eastern surgical philosophy and Western multimodal treatment strategies. Surgical Innovation: Robotic surgery has transformed the technical execution of LPLND. Its stable, high-definition three-dimensional visualization, wristed instruments, and enhanced precision enable meticulous dissection across four anatomically defined planes: the medial plane (uretero-hypogastric fascia), intermediate plane (vesico-hypogastric fascia), lateral plane (pelvic sidewall), and dorsal plane (pelvic floor and lumbosacral trunk/sacral plexus). These features facilitate consistent nerve-sparing surgery, reduce blood loss, and improve postoperative urinary and sexual function compared with conventional laparoscopy or open approaches. Robotic LPLND therefore represents a contemporary synthesis of Eastern surgical precision and Western evidence-based multimodal therapy-offering an integrated pathway toward optimized oncologic control and enhanced functional outcomes.

Background: Genetic studies have found that a germline BRCA1 gene mutation is the origin of highly increased cancer risk. Clinical studies have suggested that increased cancer risk in type-2 diabetes may be attributed to unhealthy lifestyle factors and bad habits.

Purpose: Patients with either BRCA1 gene mutation or type-2 diabetes similarly exhibit increased cancer risk, insulin resistance, and fertility disorders. It was suggested that these three alterations derive from a common genomic failure, and its recognition may shed light on the unsolved secret of cancer.

Results: (1) Germline mutations on ESR1, BRCA1, and CYP19A genes encoding estrogen receptor alpha (ERα), genome safeguarding BRCA1 protein, and CYP19 aromatase enzyme cause genomic instability. BRCA1 and ESR1 gene mutations specifically cause breast cancer, while error in the CYP19A gene leads to cancers in the endometrium, ovaries, and thyroid. (2) ERα, BRCA1, and CYP19 aromatase proteins are transcription factors creating the crucial DNA stabilizer circuit driven by estrogen regulation. Liganded ERα drives a second regulatory circuit to also control cell proliferation, in partnership with various growth factors. In a third regulatory circuit, liganded ERα drives cellular glucose supply in close interplay with insulin, IGF-1, and glucose transporters. (3) Impaired expression or activation of each transcription factor of the triad leads to defective estrogen signaling and endangers regular cell proliferation, insulin sensitivity, and fertility. (4) Impaired estrogen signaling caused by either genetic or lifestyle factors alarms the hypothalamus, which issues neural and hormonal commands throughout the body to restore estrogen signaling. (5) When the compensatory actions cannot restore estrogen signaling, the breakdown of genomic regulation leads to cancer initiation. (6) Lifestyle factors that upregulate estrogen signaling decrease cancer risk, while downregulating estrogen signaling increases it.

Conclusions: Increased cancer risk, insulin resistance, and infertility all originate from defective estrogen signaling.

Background/Objectives: Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy have become the standard of care for HR+/HER2- metastatic breast cancer. Given the metabolic functions of CDK4/6 and the endocrine activity of adipose tissue, body mass index has been proposed as a potential prognostic or predictive factor in this setting. This systematic review aimed to summarize current evidence on the association between BMI and treatment outcomes in HR+/HER2- MBC patients receiving CDK4/6i. Methods: A systematic literature search was conducted in PubMed and Scopus databases, covering publications from 2015 to 2025. We included real-world studies and clinical cohorts reporting survival outcomes of HR+/HER2- MBC patients treated with CDK4/6i in relation to BMI and other body composition parameters. Results: From 69 records identified, 14 studies met the inclusion criteria. Findings were heterogenous; four studies reported improved survival outcomes in higher BMI patients, whereas most identified no significant association. Studies incorporating computed tomography-based metrics demonstrated that body composition parameters such as visceral adiposity and skeletal muscle area were more reliable predictors of prognosis than BMI alone. Conclusions: Our findings indicate that BMI as a standalone metric is an insufficient predictor of clinical outcomes or treatment response for those receiving CDK4/6i, highlighting the need for precise body composition evaluation. More detailed anthropometric and metabolic profiling could clarify the clinical significance of adiposity in HR+/HER2- MBC.