How Early Can Pancreatic Cancer Be Recognized A Case Report and Review of the Literature

Nai, Qiang; Luo, Hongxiu; Zhang, Ping; Hossain, M. Amzad; Gu, Ping; Sidhom, Ibrahim; Mathew, Teena; Islam, Mohammed A.; Yousif, Abdalla; Sen, Shuvendu

doi:10.1159/000375121

Cited by 6 publications

(6 citation statements)

References 14 publications

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“…The probable early clinical symptoms like thromboembolism and new-onset type II diabetes occur much earlier, though the symptoms are not necessarily associated with pancreatic cancer. The early stage progress of the disease could be much slower than previously thought, giving patients with early diagnosis a much better survival probability [ 3 ]. To date, the diagnosis is based on clinical signs and pathology even though the early symptoms are vague and non-definitive.…”

Section: Introductionmentioning

confidence: 99%

Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis

Rajamani

Bhasin

2016

Genome Med

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BackgroundPancreatic cancer is an aggressive cancer with dismal prognosis, urgently necessitating better biomarkers to improve therapeutic options and early diagnosis. Traditional approaches of biomarker detection that consider only one aspect of the biological continuum like gene expression alone are limited in their scope and lack robustness in identifying the key regulators of the disease. We have adopted a multidimensional approach involving the cross-talk between the omics spaces to identify key regulators of disease progression.MethodsMultidimensional domain-specific disease signatures were obtained using rank-based meta-analysis of individual omics profiles (mRNA, miRNA, DNA methylation) related to pancreatic ductal adenocarcinoma (PDAC). These domain-specific PDAC signatures were integrated to identify genes that were affected across multiple dimensions of omics space in PDAC (genes under multiple regulatory controls, GMCs). To further pin down the regulators of PDAC pathophysiology, a systems-level network was generated from knowledge-based interaction information applied to the above identified GMCs. Key regulators were identified from the GMC network based on network statistics and their functional importance was validated using gene set enrichment analysis and survival analysis.ResultsRank-based meta-analysis identified 5391 genes, 109 miRNAs and 2081 methylation-sites significantly differentially expressed in PDAC (false discovery rate ≤ 0.05). Bimodal integration of meta-analysis signatures revealed 1150 and 715 genes regulated by miRNAs and methylation, respectively. Further analysis identified 189 altered genes that are commonly regulated by miRNA and methylation, hence considered GMCs. Systems-level analysis of the scale-free GMCs network identified eight potential key regulator hubs, namely E2F3, HMGA2, RASA1, IRS1, NUAK1, ACTN1, SKI and DLL1, associated with important pathways driving cancer progression. Survival analysis on individual key regulators revealed that higher expression of IRS1 and DLL1 and lower expression of HMGA2, ACTN1 and SKI were associated with better survival probabilities.ConclusionsIt is evident from the results that our hierarchical systems-level multidimensional analysis approach has been successful in isolating the converging regulatory modules and associated key regulatory molecules that are potential biomarkers for pancreatic cancer progression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0282-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis

Rajamani

Bhasin

2016

Genome Med

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“…Pancreatic cancer is a very challenging disease because most of the patients are already at the advanced stage before being diagnosed [ 22 , 23 ]. Despite extensive efforts in searching for effective treatments for pancreatic cancer, there has been no major breakthrough for decades.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model

Liu

et al. 2022

Cancer Cell Int

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Background Pancreatic cancer is one of the most aggressive malignancies without effective targeted therapies. MUC1 has emerged as a potential common target for cancer therapy because it is overexpressed in a variety of different cancers including the majority of pancreatic cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1 have been reported. Recently, we generated a humanized MUC1 antibody (HzMUC1) specific to the interaction region between MUC1-N and MUC1-C. In this study, we generated the antibody drug conjugate (ADC) by conjugating HzMUC1 with monomethyl auristatin (MMAE), and examined the efficacy of HzMUC1-MMAE against the MUC1-positive pancreatic cancer in vitro and in vivo. Methods Western blot and immunoprecipitation were used to detect MUC1 in pancreatic cancer cells. MUC1 localization in pancreatic cancer cells was determined by confocal microscopy. HzMUC1 was conjugated with the monomethyl auristatin (MMAE), generating the HzMUC1-MMAE ADC. Colony formation assay and flow cytometry were used to assess the effects of the HzMUC1-MMAE cell viability, cell cycle progression and apoptosis. Capan-2 and CFPAC-1 xenograft model were used to test the efficacy of HzMUC1-MMAE against pancreatic cancer. Results HzMUC1 antibody binds to MUC1 on the cell surface of pancreatic cancer cells. HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in pancreatic cancer cells. Importantly, HzMUC1-MMAE significantly reduced the growth of pancreatic xenograft tumors by inhibiting cell proliferation and enhancing cell death. Conclusion Our results indicate that HzMUC1-ADC is a promising novel targeted therapy for pancreatic cancer. HzMUC1-ADC should also be an effective drug for the treatment of different MUC1-positive cancers.

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“…Pancreatic cancer is a difficult disease to treat because many patients remain undiagnosed until their cancer is advanced [ 2 , 22 ]. Despite extensive efforts to develop pancreatic cancer therapies, there has been no improvement for decades.…”

Section: Discussionmentioning

confidence: 99%

“…Despite extensive efforts to develop pancreatic cancer therapies, there has been no improvement for decades. The most difficult hurdle to treating pancreatic cancer is the dearth of early symptoms and therefore the late diagnosis of advanced disease [ 22 ]. Another reason pancreatic cancer therapies remain often ineffective is that most therapeutics has focused on chemotherapy with cytotoxic drugs, which have limited effect on overall survival [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

A Novel Monoclonal Antibody Targets Mucin1 and Attenuates Growth in Pancreatic Cancer Model

Maharjan

Kim

et al. 2018

IJMS

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Mucin1 (MUC1) is a highly glycosylated transmembrane protein that plays a crucial role in the lubrication and protection of normal epithelial cells. However, MUC1 has emerged as a potential target for cancer therapy because it is overexpressed and functions in several types of cancers. Recently, we produced a monoclonal antibody (the anti-hMUC1 antibody) specific to the extracellular region of the MUC1 subunit MUC1-C to evaluate the utility of using anti-MUC1 antibodies in pancreatic cancer models. The anti-hMUC1 antibody recognized the MUC1-C protein in pancreatic cancer cells. Based on immunostaining and confocal image analyses, the anti-hMUC1 antibody initially bound to the cell membrane then was internalized in cancer cells that express MUC1. The anti-hMUC1 antibody suppressed epidermal growth factor (EGF)-mediated extracellular signal–regulated kinase (ERK) phosphorylation and cyclin D1 expression. When the anti-hMUC1 antibody was injected into a xenograft mouse model and traced using an in vivo imaging system, we observed that the anti-hMUC1 antibody was localized to MUC1-expressing pancreatic tumors. Importantly, the anti-hMUC1 monoclonal antibody suppressed pancreatic tumor growth in mice. According to immunohistochemistry analysis using a pancreatic cancer tissue array and the anti-hMUC1 antibody, MUC1 was highly expressed in human pancreatic cancer tissues compared to normal tissues. Therefore, we conclude that the anti-hMUC1 antibody specifically targets MUC1 and suppresses its function in pancreatic cancer in vitro and in vivo and can be further developed as a promising targeted therapy to treat pancreatic cancer.

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How Early Can Pancreatic Cancer Be Recognized A Case Report and Review of the Literature

Cited by 6 publications

References 14 publications

Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis

Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis

Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model

A Novel Monoclonal Antibody Targets Mucin1 and Attenuates Growth in Pancreatic Cancer Model

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