Targeting lipid metabolism: novel insights and therapeutic advances in pancreatic cancer treatment

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 13, 2025

Lipid metabolism in cancer is characterized by dysregulated lipid regulation and utilization, critical for promoting tumor growth, survival, resistance to therapy. Pancreatic (PC) a highly aggressive malignancy of the gastrointestinal tract that has dismal 5-year survival rate less than 10%. Given essential function pancreas digestion, progression severely disrupts its function. Standard treatments PC such as surgical resection, chemotherapy, radiotherapy. However, these therapies often face significant challenges, including biochemical recurrence drug resistance. limitations, new therapeutic approaches are being developed target metabolism. Dysregulation cholesterol biosynthesis alterations fatty acids (FAs), palmitate, stearate, omega-3, omega-6, have been observed pancreatic cancer. These lipids serve energy sources, signaling molecules, components cell membranes. Their accumulation fosters an immunosuppressive microenvironment supports proliferation metastasis. Moreover, dysregulation within immune cells, particularly T impairs surveillance weakens body's defenses against Abnormal also contributes PC. Despite targeting may offer promising strategy. By enhancing peroxidation, induction ferroptosis—a form regulated death—could impair cells hinder disease progression.

Language: Английский

---

Targeting of the G9a, DNMT1 and UHRF1 epigenetic complex as an effective strategy against pancreatic ductal adenocarcinoma

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 15, 2025

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options and poor prognosis. The critical role of epigenetic alterations such as changes in DNA methylation, histones modifications, chromatin remodeling, pancreatic tumors progression becoming increasingly recognized. Moreover, PDAC these aberrant mechanisms can also limit therapy efficacy. This study aimed to investigate the expression prognostic significance key complex encompassing methyltransferase-1 (DNMT1), histone methyltransferase G9a, scaffold protein UHRF1 PDAC. We evaluated therapeutic potential an innovative inhibitor targeting effectors. Methods Immunohistochemical analysis DNMT1, was conducted human tissue samples. Staining semi-quantitatively scored, overexpression defined moderate strong positivity. impact assessed by correlating patient survival. antitumoral effects dual DNMT1-G9a CM272 were tested cell lines, followed transcriptomic analyses identify underlying mechanisms. vivo efficacy xenograft syngeneic mouse models, both alone combination anti-PD1 immunotherapy. Results significantly overexpressed cells stroma compared normal tissues. Simultaneous three proteins associated reduced survival resected patients. exhibited potent antiproliferative activity inducing apoptosis altering metabolic cycle-related genes. enhanced chemotherapy sensitivity inhibited tumor growth without detectable toxicity. Combination further improved antitumor responses immune infiltration, particularly CD4 + CD8 T cells. Conclusions combined predictor CM272, this complex, shows promising apoptosis, reprogramming pathways, enhancing responses. immunotherapy offers novel, effective strategy for

Language: Английский

---

Cholesterol metabolism in pancreatic cancer and associated therapeutic strategies

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2024, Volume and Issue: 1870(2), P. 159578 - 159578

Published: Nov. 13, 2024

Pancreatic cancer remains one of the most lethal cancers due to late diagnosis and high chemoresistance. Despite recent progression in development chemotherapies, immunotherapies, potential nanoparticles-based approaches, success rate therapeutic response is limited which further compounded by drug resistance. Understanding emerging biological molecular pathways causative pancreatic cancer's aggressive chemoresistance vital improve effectiveness existing therapeutics develop new therapies. One such under-investigated relatively less explored area research documenting effect that lipids, specifically cholesterol, its metabolism, impose on cancer. Dysregulated cholesterol metabolism has a profound role supporting cellular proliferation, survival, promoting this been well established various other cancers. Thus, we aimed provide an in-depth review focusing significance relevant genes at play, processes contributing homeostasis, current efforts cholesterol-targeting therapeutics. We highlight caveats, weigh different experimental strategies, possible suggestions for future highlighting cholesterol's importance as target against resistance progression.

Language: Английский

---

Cytochrome P450 3A gene family in gastric cancer: Unveiling diagnostic biomarkers and therapeutic targets for personalized treatment

World Journal of Clinical Oncology, Journal Year: 2025, Volume and Issue: 16(4)

Published: March 26, 2025

The cytochrome P450 3A (CYP3A ) gene family’s role in early progression of gastric cancer was comprehensively investigated. Its potential as a therapeutic target evaluated. Upon literature review, aberrant expression the CYP3A family has strong correlation with onset, although precise underlying mechanisms remain unclear. To assess its biomarker for diagnosis and target, we have provided comprehensive review regulatory governing cancer, well relation tumor microenvironment. is crucial proliferation, migration, invasion cells promotes by modulating inflammatory responses oxidative stress within Furthermore, genetic polymorphisms enzymes highlight value personalized medicine. Based on these findings, this paper explores feasibility developing inhibitors activators targeting discusses applications therapy. This research provides theoretical support an diagnostic marker cancer. In future, multi-omics studies large-scale clinical trials will be essential to advance translation findings.

Language: Английский

---

The impact of diabetes, hypercholesterolemia, and low-density lipoprotein (LDL) on the survival of cervical cancer patients

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 14, 2024

Cervical cancer is a prevalent malignancy and an important health concern worldwide. Recent research has highlighted the potential impact of metabolic factors, such as hyperlipidemia diabetes, on progression, increased mortality, patient outcomes. However, insufficient data have been reported regarding their relationship with cervical cancer. This study aimed to investigate relationships between disorders, including dyslipidemia, dysglycemia, syndrome, survival in patients We retrospectively analyzed demographic information, clinical characteristics, indicators Patients were categorized into groups based specific conditions: high triglyceride, low-density lipoprotein, cholesterol, diabetes groups. Additionally, presence syndrome other comorbidities was recorded. The log-rank test used compare rates different identify associated risk factors. Survival curves generated via Cox proportional hazards model evaluate associations parameters survival. analyze from 840 28 72 years old who underwent surgery. hazard ratio (HR) mortality 1.804 (95% CI 1.394–2.333, p < 0.001) high-density lipoprotein group, 0.758 0.558 1.030, high-triglyceride 1.794 1.304–2.470, 0.011 0.005–0.025, group. These factors significantly reduced cancer, these persisted after adjusting for age, stage, treatment type, or comorbidities. highlights importance significance controlling hyperlipidemia, improve outcomes Future should explore managing multiple conditions prognosis patients.

Language: Английский

---

Cholesterol Metabolism-Mediated Immune Regulation and Cancer Immunotherapy

Published: Jan. 1, 2024

Download This Paper Open PDF in Browser Add to My Library Share: Permalink Using these links will ensure access this page indefinitely Copy URL DOI

Language: Английский

---

Diet predisposes to pancreatic cancer through cellular nutrient sensing pathways

FEBS Letters, Journal Year: 2024, Volume and Issue: 598(20), P. 2470 - 2481

Published: June 17, 2024

Pancreatic cancer is a lethal disease with limited effective treatments. A deeper understanding of its molecular mechanisms crucial to reduce incidence and mortality. Epidemiological evidence suggests link between diet risk, though dietary recommendations for at‐risk individuals remain debated. Here, we propose that cell‐intrinsic nutrient sensing pathways respond specific diet‐derived cues facilitate oncogenic transformation pancreatic epithelial cells. This review explores how influences predisposition through downstream consequences (pre‐)cancer cell biology. We also examine experimental connecting food intake progression, highlighting as promising target therapeutic development mitigate risk.

Language: Английский

---

Establishment of a prognostic model for pancreatic cancer based on mitochondrial metabolism related genes

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 28, 2024

Pancreatic ductal adenocarcinoma (PAAD) is recognized as an exceptionally aggressive cancer that both highly lethal and unfavorable prognosis. The mitochondrial metabolism pathway intimately involved in oncogenesis tumor progression, however, much remains unknown this area. In study, the bioinformatic tools have been used to construct a prognostic model with metabolism-related genes (MMRGs) evaluate survival, immune status, mutation profile, drug sensitivity of PAAD patients.

Language: Английский

---