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Molecular Advances in Pancreatic Cancer
Pancreatic cancer (PC) has become the fourth leading cause of cancer-related deaths in America, and the incidence is on the rise. However, the diagnosis and treatment of PC remain a huge challenge. With the advent of "omics" research, global analysis of biological systems at the molecular level using high-throughput technologies has led to new advances in improving the diagnosis and treatment of PC. Alfa Cytology is a CRO company comprised of scientists, bioinformaticians, oncologists, and so on. Our team works closely and communicates actively to achieve our common goals of helping researchers and professionals understand PC biology, explore new PC therapeutics and protocols, and develop new PC biomarkers.
Molecular understanding of PC
- Genomic subtypes of PC
Recent genomic analysis revealed some major mutated genes in pancreatic ductal adenocarcinoma (PDAC), such as KRAS, TP53, CDKN2A, and SMAD4. According to the quantity of variations in chromosome structure, PDAC can be categorized into four subtypes, stable, locally rearranged, scattered, and unstable. Among them, the unstable subtype was related to a high breast cancer gene (BRCA) mutational signature, suggesting defects in DNA damage repair. In addition, a study using real-time targeted sequencing of exons and introns from thousands of PDAC samples identified genetic alterations in DNA damage repair, cell cycle control, receptor tyrosine kinase (RTK)/Ras/mitogen-activated protein kinase (MAPK) activation, TGF-B signaling, histone modifications and so on. In addition to mutations in DNA damage repair genes (BRCA-FANC family) in 14% of the samples, mutations in RTK genes were present in 12% of the samples, suggesting that RTK could be another potential target in the context of wild-type KRAS PDAC. - Proteomic subtypes of PC
A proteomics study using liquid chromatography-mass spectrometry (LC-MS/MS) in PDAC liver transfer specimens identified 916 proteins. These proteins have been found to be involved in many functions, including protein processing and transport, translation, extracellular matrix organization, glycolytic processes, immune response, cellular homeostasis, etc. These proteins were analyzed and classified into four PDAC subtypes and three protein clusters, including inflammatory, proliferative, progenitor-like and metabolic subtypes, corresponding to protein cluster 3 (pentose phosphate pathway, adaptive immune response, complement activation, IL8 production, and extracellular fibril organization), cluster 2 (translation, cell proliferation, and telomere maintenance), cluster 1 (ethanol oxidation pathways, mitochondrial fatty acid B-oxidation and retinoic acid signaling pathways) and cluster1, respectively. - Metabolomic subtypes of PC
Metabolomics analysis using LC-MS/MS and gas chromatography-MS identified and quantified 256 metabolites in 38 PDAC-derived cell lines. According to these metabolites, PDAC can be stratified into three subtypes, including slow proliferating, glycolytic, and lipogenic.
Diagnosis and detection of PC: new biomarkers are still needed
To achieve an early diagnosis of PC, new and more sensitive biomarkers need to be discovered and developed. Considerable research has been done on biomarker detection in blood, breath, and pancreatic fluid. The investigation of potential biomarkers, such as liquid biopsies, to aid in the screening, diagnosis, and treatment of PC has been an area of intensive research. Here, we summarize some biomarkers with potential for early diagnosis, prediction, and prognostic indications of PC.
| Summary of biomarkers with potential for early diagnosis, prediction and prognostic indications of PC | ||
|---|---|---|
| Diagnostic markers | Predictive biomarkers | Prognostic markers |
| Serum carbohydrate antigen (CA) 19-9 | Serum carbohydrate antigen (CA) 19-9 | |
| MicroRNA (miRNAs) | Human equilibrate nucleoside transporter 1 (hENT1) | SMAD4, signal transformer from transforming growth factorbeta (TGF-β) |
| Macrophage inhibitory cytokine 1 (MIC-1) | FOLFIRINOX markers | Angiogenesis markers |
| PAM 4 (a murine monoclonal antibody) | Inflammatory markers | |
| Glypican 1 (GPC1, a membrane anchoring protein) | Stromal markers | Immune markers |
| KRAS mutation | BRCA mutated tumors | MicroRNA (miRNAs) |
| Osteopontin (OPN, a protein of extracellular matrix) | Microsatellite instability | SPARC |
| Epigenetic markers | PD-1/PD-L1 | |
How can we help you?
Based on advanced platforms and years of experience in the PC field, Alfa Cytology is committed to providing our customers with optimal customized services and solutions to meet the specific needs of their projects. Our services include but are not limited to the following list:
- Further exploration of the molecular mechanisms underlying the initiation, progression, and maintenance of PC.
- Discovery of new molecular targets driving PC initiation, progression, and metastasis that can be used as new therapeutic or treatment targets.
- Preclinical evaluation of new anticancer drugs and strategies for PC.
- Screening and identification of new validated biomarkers for early detection of PC.
In order to get more details about our services, please contact us. We've got everything covered for your needs.
References
- Hasan, S., Jacob, R., Manne, U., & Paluri, R. (2019). Advances in pancreatic cancer biomarkers. Oncology reviews, 13(1).
- Rajesh, S., Cox, M. J., & Runau, F. (2021). Molecular advances in pancreatic cancer: A genomic, proteomic and metabolomic approach. World Journal of Gastroenterology, 27(31), 5171.
