Ephrin Receptor A2 Research Articles

BCL6 overexpression in CD4+ T cells induces Tfh-like transdifferentiation and enhances antitumor efficiency of CAR-T therapy in pancreatic cancer

PDAC is a typical “cold tumor” characterized by low immune cell infiltration and a suppressive immune microenvironment. We previously observed the existence of a rare group of follicular helper T cells (Tfh) that could enhance antitumor immune responses by recruiting other immune cells in PDAC. In this study, we ectopically expressed BCL6 in CD4+ T cells, and successfully induced Tfh-like transdifferentiation in vitro. This strategy provided abundant Tfh-like cells (iTfhs) that can recruit CD8+ T cells like endogenous Tfhs. Subsequently, Chimeric Antigen Receptors (CARs) against both MSL (Mesothelin) and EPHA2 (Ephrin receptor A2) were used to modify iTfh cells, and the CAR-iTfh cells significantly improved infiltration and antitumor cytotoxicity of co-cultured CD8+ T cells. After that, combinatory administration of CAR-iTfh & CAR-CD8 T cell therapy displayed a better effect in repressing the PDAC tumors in xenograft mouse models, compared to conventional CAR-CD4 & CAR-CD8 combinations, and the models received the CAR-iTfh & CAR-CD8 T cells displayed a significantly improved survival rate. Our study revealed the plasticity of Thelper differentiation, expanded the source of Tfh-like cells for cell therapy, and demonstrated a novel and potentially more efficient cellular composition for CAR-T therapy.

EphA2 promotes the transcription of KLF4 to facilitate stemness in oral squamous cell carcinoma

Ephrin receptor A2 (EphA2), a member of the Ephrin receptor family, is closely related to the progression of oral squamous cell carcinoma (OSCC). Cancer stem cells (CSCs) play essential roles in OSCC development and occurrence. The underlying mechanisms between EphA2 and CSCs, however, are not yet fully understood. Here, we found that EphA2 was overexpressed in OSCC tissues and was associated with poor prognosis. Knockdown of EphA2 dampened the CSC phenotype and the tumour-initiating frequency of OSCC cells. Crucially, the effects of EphA2 on the CSC phenotype relied on KLF4, a key transcription factor for CSCs. Mechanistically, EphA2 activated the ERK signalling pathway, promoting the nuclear translocation of YAP. Subsequently, YAP was bound to TEAD3, leading to the transcription of KLF4. Overall, our findings revealed that EphA2 can enhance the stemness of OSCC cells, and this study identified the EphA2/KLF4 axis as a potential target for treating OSCC.

Comprehensive analysis of EphA2 in pan-cancer: A prognostic biomarker associated with cancer immunity.

Several studies have reported a significant relationship between Ephrin receptor A2 (EphA2) and malignant progression in numerous cancers. However, there is a lack of comprehensive pan-cancer analysis on the prognostic value, mutation status, methylation landscape, and potential immunological function of EphA2. Using The Cancer Genome Atlas, Genotype Tissue Expression Database and GEO data, we analysed the differences in EphA2 expression between normal and tumour tissues and the effects of EphA2 on the prognosis of different tumours. Furthermore, using GSCALite, cBioPortal, TISDB, ULCLAN and TIMER 2.0 databases or platforms, we comprehensively analysed the potential oncogenic mechanisms or manifestations of EphA2 in 33 different tumour types, including tumour mutation status, DNA methylation status and immune cell infiltration. The correlation of EphA2 with immune checkpoints, tumour mutational burden, DNA microsatellite instability and DNA repair genes was also calculated. Finally, the effects of EphA2 inhibitors on the proliferation of human glioma and lung cancer cells were verified in cellular experiments. EphA2 is differentially expressed in different tumours, and patients with overexpression have poorer overall survival. In addition, gene mutations, gene copy number variation and DNA/RNA methylation of EphA2 have been identified in various tumours. Moreover, EphA2 is positively associated with immune infiltration involving macrophages and CD8+ T cells. Further, EphA2 mRNA expression is significantly associated with immune checkpoint in various cancers, especially programmed death-ligand 1. Finally, the EphA2 inhibitor ALW-II-41-27 shows potent anti-tumour activity. Our first pan-cancer study of EphA2 provides insight into the prognostic and immunological roles of EphA2 in different tumours, suggesting that EphA2 might be a potential biomarker for poor prognosis and immune infiltration in cancer.

Interferon-induced transmembrane protein-1 competitively blocks Ephrin receptor A2-mediated Epstein-Barr virus entry into epithelial cells.

Epstein-Barr virus (EBV) can infect both B cells and epithelial cells (ECs), causing diseases such as mononucleosis and cancer. It enters ECs via Ephrin receptor A2 (EphA2). The function of interferon-induced transmembrane protein-1 (IFITM1) in EBV infection of ECs remains elusive. Here we report that IFITM1 inhibits EphA2-mediated EBV entry into ECs. RNA-sequencing and clinical sample analysis show reduced IFITM1 in EBV-positive ECs and a negative correlation between IFITM1 level and EBV copy number. IFITM1 depletion increases EBV infection and vice versa. Exogenous soluble IFITM1 effectively prevents EBV infection in vitro and in vivo. Furthermore, three-dimensional structure prediction and site-directed mutagenesis demonstrate that IFITM1 interacts with EphA2 via its two specific residues, competitively blocking EphA2 binding to EBV glycoproteins. Finally, YTHDF3, an m6A reader, suppresses IFITM1 via degradation-related DEAD-box protein 5 (DDX5). Thus, this study underscores IFITM1's crucial role in blocking EphA2-mediated EBV entry into ECs, indicating its potential in preventing EBV infection.

In silico docking study of selected compounds for its hepatoprotective activity

Liver fibrosis is a condition characterized by the excessive accumulation of scar tissue in the liver. It is typically caused by chronic liver diseases, such as chronic viral hepatitis (e.g., hepatitis B and C), alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis, and certain genetic conditions. Ephrin receptor A2 (EphA2) is identified as potential anti-inflammatory target which influences inflammatory process and immune response, impacting the recruitment and activation of immune cells and as a host cofactor for Hepatitis C Virus (HCV) entry. Andrographolide a diterpenoid lactone, Scoulerine a natural alkaloid possess anti-inflammatory activity. The present work was done to evaluate anti-inflammatory activity of andrographolide and scoulerine using software Autodock 4.2. Phyto-constituents were fetched from the PubChem database. 3D structure of EphA2 were downloaded from Protein Data Bank (PDB). Among two phyto compounds, andrographolide had highest binding energy of -7.58 which is a clear evident of potential anti-inflammatory activity and prevent hepatic fibrosis. The active site of the target protein was predicted by using CASTP (Computed atlas of surface topography of proteins). Protein ligand interaction information is obtained by Protein ligand interaction profiler.

Identification of therapeutic targets and prognostic biomarkers of the ephrin receptor subfamily in pancreatic adenocarcinoma.

We aimed to examine the significance of ephrin receptor A2 (EphA2) expression in pancreatic adenocarcinoma (PAAD) and its associated mechanism. EphA2 mRNA expression patterns were compared in pancreatic cancer and normal tissues using GEPIA. Kaplan-Meier analysis was used to examine the correlation between EphA2 expression and PAAD patient prognosis. EphA2 gene methylation and associations with tumor immune cell infiltration were analyzed with UALCAN and TIMER, respectively. EphA2-interacting proteins were investigated with GeneMANIA, while STRING helped predict potentially relevant signaling pathways. EphA2 protein expression was examined with immunohistochemistry (IHC) in PAAD patient tissues. EphA2 was highly expressed in pancreatic cancer tissues and associated with pathological stage. PAAD patients with high EphA2 expression had shorter overall survival and disease-free survival times. EphA2 expression levels were significantly and positively associated with CD4+ T cell infiltration. EphA2 can interact with ENFNA1, ACP1, and CDC42. High EphA2 mRNA expression was enriched for regulation of cell size and cell proliferation. IHC assays suggested that pancreatic cancer tissues had higher EphA2 protein levels than normal pancreatic tissues. EphA2 is highly expressed in PAAD and closely related to poor patient prognosis, and is therefore a potential biomarker and target for PAAD diagnosis and treatment.

Downregulation of EphA2 stability by RNF5 limits its tumor-suppressive function in HER2-negative breast cancers

Ephrin receptor A2 (EphA2) plays dual functions in tumorigenesis through ligand-independent tumor promotion or ligand-dependent tumor suppression. However, the regulation of EphA2 tumor-suppressive function remains unclear. Here, we showed that RNF5 interacts with EphA2 and induces its ubiquitination and degradation, decreases the stability and cell surface distribution of EphA2 and alters the balance of its phosphorylation at S897 and Y772. In turn, RNF5 inhibition decreases ERK phosphorylation and increases p53 expression through an increase in the EphA2 level in HER2-negative breast cancer cells. Consequently, RNF5 inhibition increases the adhesion and decreases the migration of HER2-negative breast cancer cells, and RNF5 silencing suppresses the growth of xenograft tumors derived from ER-positive, HER2-negative breast cancer cells with increased EphA2 expression and altered phosphorylation. RNF5 expression is inversely correlated with EphA2 expression in breast cancers, and a high EphA2 level accompanied by a low RNF5 level is related to better survival in patients with ER-positive, HER2-negative breast cancers. These studies revealed that RNF5 negatively regulates EphA2 properties and suppresses its tumor-suppressive function in HER2-negative breast cancers.

Potential of Hepatoprotective Activity of Abelmoschus Moschatus Seed: In-Silico Validation

A type of wound healing known as hepatic fibrosis arises in response to chronic liver damage brought on by viruses, toxins, and medications that are detrimental to the liver. The syndrome is characterized by inflammation, which is followed by the deposition of extracellular matrix proteins and the development of scar tissue. Ephrin receptor A2 is a host cofactor that has been associated to Hepatitis C virus (HCV) entry (EphA2). The Abelmoschus moschatus seed belong to family Malvaceae. It contains sitosterol b. total phenol, flavonoids which are responsible for antioxidant, antimicrobial and free radical scavenging activity. The exact mechanism of action for the hepatoprotective action of Myricetin was still not revealed. With intent to propose the most probable mechanism of action of Myricetin the docking based computational analysis has been performed against the hepatoprotective drug targets like PPARα enzyme.

Potential of Hepatoprotective Activity of Abelmoschus Moschatus Seed: In-Silico Validation

A type of wound healing known as hepatic fibrosis arises in response to chronic liver damage brought on by viruses, toxins, and medications that are detrimental to the liver. The syndrome is characterized by inflammation, which is followed by the deposition of extracellular matrix proteins and the development of scar tissue. Ephrin receptor A2 is a host cofactor that has been associated to Hepatitis C virus (HCV) entry (EphA2). The Abelmoschus moschatus seed belong to family Malvaceae. It contains sitosterol b. total phenol, flavonoids which are responsible for antioxidant, antimicrobial and free radical scavenging activity. The exact mechanism of action for the hepatoprotective action of Myricetin was still not revealed. With intent to propose the most probable mechanism of action of Myricetin the docking based computational analysis has been performed against the hepatoprotective drug targets like PPARα enzyme. Research Article

Hepatoprotective Efficacy of Selegiline: Molecular Insight

Liver fibrosis is a form of wound healing that develops in response to persistent liver injury brought on by viruses, poisons, and medicines that are harmful to the liver. Inflammation is a hallmark of the condition, which is then followed by the formation of scar tissue via the deposition of extracellular matrix proteins. Hepatitis C virus (HCV) entrance has been linked to the host cofactor ephrin receptor A2 (EphA2). Selegiline hydrochloride is a levorotatory acetylenic derivative of phenethylamine. It is commonly referred to in the clinical and pharmacological literature as l-deprenyl. Selegiline (deprenyl) is a selective inhibitor of cerebral monoamine oxidase type B at the dosage (10 mg/day) used in patients with Parkinson's disease. Through this activity, the drug increases nigrostriatal dopamine levels, and may protect neurons against damage by free radicals and possibly exogenous neurotoxins.The exact mechanism of action for the hepatoprotective action of Selegiline was still not revealed. With intent to propose the most probable mechanism of action of Selegiline the docking based computational analysis has been performed against the hepatoprotective drug targets like PPARα enzyme.

Cytomegalovirus US28 regulates cellular EphA2 to maintain viral latency.

Cytomegalovirus (CMV) reactivation from latency following immune dysregulation remains a serious risk for patients, often causing substantial morbidity and mortality. Here, we demonstrate the CMV-encoded G protein-coupled receptor, US28, in coordination with cellular Ephrin receptor A2, attenuates mitogen-activated protein kinase signaling, thereby limiting viral replication in latently infected primary monocytes. Furthermore, treatment of latently infected primary monocytes with dasatinib, a Food and Drug Association-approved kinase inhibitor used to treat a subset of leukemias, results in CMV reactivation. These ex vivo data correlate with our retrospective analyses of the Explorys electronic health record database, where we find dasatinib treatment is associated with a significant risk of CMV-associated disease (odds ratio 1.58, P = 0.0004). Collectively, our findings elucidate a signaling pathway that plays a central role in the balance between CMV latency and reactivation and identifies a common therapeutic cancer treatment that elevates the risk of CMV-associated disease.

HCG11 inhibits salivary adenoid cystic carcinoma by upregulating EphA2 via binding to miR-1297

Ephrin receptor A2 (EphA2) was reported to be related to the tumorigenesis of salivary adenoid cystic carcinoma (SACC), which is a rare malignancy accounting for less than 1% of all oral and maxillofacial tumors. This research aimed to assess the molecular mechanisms of EphA2 in SACC. The expression of long non-coding RNA human leukocyte antigen complex group 11 (HCG11), microRNA-1297 (miR-1297), and EphA2 in SACC cell lines compared with normal human salivary gland (HSG) cell line was measured by reverse transcription-quantitative polymerase chain reaction. EphA2 protein level was detected by western blot. 5-ethynyl-2'-deoxyuridine (EdU), colony formation, Transwell, and wounding healing experiments were applied to evaluate SACC cell proliferation, migration, and invasion. The relationship among HCG11, miR-1297, and EphA2 was confirmed by luciferase reporter, RNA pulldown, and RNA immunoprecipitation experiments. HCG11 and EphA2 were downregulated while miR-1297 was upregulated in SACC cells. EphA2 overexpression suppressed SACC cell proliferation, migration, and invasion. HCG11 bound to miR-1297 to reduce the inhibition of miR-1297 on EphA2 expression. EphA2 knockdown reversed the suppression of HCG11 overexpression on SACC cell phenotypes. This study identified the HCG11/miR-1297/EphA2 regulatory axis in SACC, which might provide novel therapeutic targets for SACC.

Hepatoprotective Potential of Caesalpinia bonducella: Molecular Insight

Liver fibrosis is a wound healing process initiated in response to chronic liver damage caused by viruses, toxins, and hepatotoxic drugs. The disease is characterized by inflammation followed by deposition of extracellular matrix proteins to form scar tissue. Ephrin receptor A2 (EphA2) has been identified as a host cofactor for hepatitis C virus (HCV) entry. The plant Caesalpinia bonducella is used in a variety of systems a traditional medicine used to treat human ailments and affiliation prickly shrub belonging to the Caesalpiniaceae family found throughout the world, especially tropical region. It is a very valuable medicinal plant because all parts of the plant have medicinal properties. It was like traditional Indian herbal medicine considered an important therapeutic modality for the treatment of various diseases. As per literature survey the plants containing kaempferol and quercetin-3-methylether are traditionally utilized for the cure of cancer and liver related disorders from the immortal time. The exact mechanism of action for the hepatoprotective action of kaempferol and quercetin-3-methylether was still not revealed. With intent to propose the most probable mechanism of action of kaempferol and quercetin-3-methylether the docking based computational analysis has been performed against the hepatoprotective drug targets like PPARα enzyme.

Hepatoprotective Potential of Caesalpinia bonducella: Molecular Insight

Abstract: Liver fibrosis is a wound healing process initiated in response to chronic liver damage caused by viruses, toxins, and hepatotoxic drugs. The disease is characterized by inflammation followed by deposition of extracellular matrix proteins to form scar tissue. Ephrin receptor A2 (EphA2) has been identified as a host cofactor for hepatitis C virus (HCV) entry. The plant Caesalpinia bonducella is used in a variety of systems a traditional medicine used to treat human ailments and affiliation prickly shrub belonging to the Caesalpiniaceae family found throughout the world, especially tropical region. It is a very valuable medicinal plant because all parts of the plant have medicinal properties. It was like traditional Indian herbal medicine considered an important therapeutic modality for the treatment of various diseases. As per literature survey the plants containing kaempferol and quercetin-3-methylether are traditionally utilized for the cure of cancer and liver related disorders from the immortal time. The exact mechanism of action for the hepatoprotective action of kaempferol and quercetin-3-methylether was still not revealed. With intent to propose the most probable mechanism of action of kaempferol and quercetin-3-methylether the docking based computational analysis has been performed against the hepatoprotective drug targets like PPARα enzyme.

TYROSINE KINASE INHIBITOR ALW-II-41-27 ATTENUATES OSTEOPHYTOSIS AND SYNOVITIS IN MICE

Purpose: Osteophytes and synovitis are highly prevalent in osteoarthritis (OA) and are associated with pain and disease progression. Therefore, a drug that simultaneously inhibits hypertrophy and inflammation has the potential to reduce both formation of osteophytosis and alleviate synovitis. Osteophytes originate from a cartilage outgrowth that undergoes hypertrophic differentiation followed by ossification. Previously, we have identified an increased expression of Ephrin receptor A2 (EphA2), a tyrosine kinase associated with inflammation, in osteoarthritic cartilage and in hypertrophic cartilage of the growth plate.

Mass spectrometry-based proteomic platforms for better understanding of SARS-CoV-2 induced pathogenesis and potential diagnostic approaches.

While protein–protein interaction is the first step of the SARS‐CoV‐2 infection, recent comparative proteomic profiling enabled the identification of over 11,000 protein dynamics, thus providing a comprehensive reflection of the molecular mechanisms underlying the cellular system in response to viral infection. Here we summarize and rationalize the results obtained by various mass spectrometry (MS)‐based proteomic approaches applied to the functional characterization of proteins and pathways associated with SARS‐CoV‐2‐mediated infections in humans. Comparative analysis of cell‐lines versus tissue samples indicates that our knowledge in proteome profile alternation in response to SARS‐CoV‐2 infection is still incomplete and the tissue‐specific response to SARS‐CoV‐2 infection can probably not be recapitulated efficiently by in vitro experiments. However, regardless of the viral infection period, sample types, and experimental strategies, a thorough cross‐comparison of the recently published proteome, phosphoproteome, and interactome datasets led to the identification of a common set of proteins and kinases associated with PI3K‐Akt, EGFR, MAPK, Rap1, and AMPK signaling pathways. Ephrin receptor A2 (EPHA2) was identified by 11 studies including all proteomic platforms, suggesting it as a potential future target for SARS‐CoV‐2 infection mechanisms and the development of new therapeutic strategies. We further discuss the potentials of future proteomics strategies for identifying prognostic SARS‐CoV‐2 responsive age‐, gender‐dependent, tissue‐specific protein targets.

A primary nasopharyngeal three-dimensional air-liquid interface cell culture model of the pseudostratified epithelium reveals differential donor- and cell type-specific susceptibility to Epstein-Barr virus infection.

Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus with latent and lytic cycles. EBV replicates in the stratified epithelium but the nasopharynx is also composed of pseudostratified epithelium with distinct cell types. Latent infection is associated with nasopharyngeal carcinoma (NPC). Here, we show with nasopharyngeal conditionally reprogrammed cells cultured at the air-liquid interface that pseudostratified epithelial cells are susceptible to EBV infection. Donors varied in susceptibility to de novo EBV infection, but susceptible cultures also displayed differences with respect to pathogenesis. The cultures from one donor yielded lytic infection but cells from two other donors were positive for EBV-encoded EBERs and negative for other lytic infection markers. All cultures stained positive for the pseudostratified markers CK7, MUC5AC, α-tubulin in cilia, and the EBV epithelial cell receptor Ephrin receptor A2. To define EBV transcriptional programs by cell type and to elucidate latent/lytic infection-differential changes, we performed single cell RNA-sequencing on one EBV-infected culture that resulted in alignment with many EBV transcripts. EBV transcripts represented a small portion of the total transcriptome (~0.17%). All cell types in the pseudostratified epithelium had detectable EBV transcripts with suprabasal cells showing the highest number of reads aligning to many EBV genes. Several restriction factors (IRF1, MX1, STAT1, C18orf25) known to limit lytic infection were expressed at lower levels in the lytic subcluster. A third of the differentially-expressed genes in NPC tumors compared to an uninfected pseudostratified ALI culture overlapped with the differentially-expressed genes in the latent subcluster. A third of these commonly perturbed genes were specific to EBV infection and changed in the same direction. Collectively, these findings suggest that the pseudostratified epithelium could harbor EBV infection and that the pseudostratified infection model mirrors many of the transcriptional changes imposed by EBV infection in NPC.

Inhibition of the tyrosine kinase receptor EPHA2 decreases hypertrophic differentiation of chondrocytes and mesenchymal stem cells

Purpose: During osteoarthritis, articular chondrocytes become hypertrophic leading to the degradation of cartilage extracellular matrix, promoting the progression of the disease. Therefore, a drug that inhibits hypertrophy would be a promising disease modifying OA drug. Previously, we identified that expression of Ephrin receptor A2 (EphA2), a tyrosine kinase, is increased in chondrocytes during hypertrophic differentiation in the mouse growth plate. Whether EphA2 plays a role in human articular chondrocyte hypertrophy in OA is unknown.

Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids.

Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection.

Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases.

Pancreatic cancer remains one of the most difficult malignancies to treat. Minimal improvements in patient outcomes and persistently abysmal patient survival rates underscore the great need for new treatment strategies. Currently, there is intense interest in therapeutic strategies that target tyrosine protein kinases. Here, we employed kinome arrays and bioinformatic pipelines capable of identifying differentially active protein tyrosine kinases in different patient-derived pancreatic ductal adenocarcinoma (PDAC) cell lines and wild-type pancreatic tissue to investigate the unique kinomic networks of PDAC samples and posit novel target kinases for pancreatic cancer therapy. Consistent with previously described reports, the resultant peptide-based kinome array profiles identified increased protein tyrosine kinase activity in pancreatic cancer for the following kinases: epidermal growth factor receptor (EGFR), fms related receptor tyrosine kinase 4/vascular endothelial growth factor receptor 3 (FLT4/VEGFR-3), insulin receptor (INSR), ephrin receptor A2 (EPHA2), platelet derived growth factor receptor alpha (PDGFRA), SRC proto-oncogene kinase (SRC), and tyrosine kinase non receptor 2 (TNK2). Furthermore, this study identified increased activity for protein tyrosine kinases with limited prior evidence of differential activity in pancreatic cancer. These protein tyrosine kinases include B lymphoid kinase (BLK), Fyn-related kinase (FRK), Lck/Yes-related novel kinase (LYN), FYN proto-oncogene kinase (FYN), lymphocyte cell-specific kinase (LCK), tec protein kinase (TEC), hemopoietic cell kinase (HCK), ABL proto-oncogene 2 kinase (ABL2), discoidin domain receptor 1 kinase (DDR1), and ephrin receptor A8 kinase (EPHA8). Together, these results support the utility of peptide array kinomic analyses in the generation of potential candidate kinases for future pancreatic cancer therapeutic development.