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Integrative landscape of dysregulated signaling pathways of clinically distinct pancreatic cancer subtypes.

ABSTRACT: Despite modern therapeutic advances, the survival prospects of pancreatic cancer patients have remained poor. Besides being highly metastatic, pancreatic cancer is challenging to treat because it is caused by a heterogeneous array of somatic mutations that impact a variety of signaling pathways and cellular regulatory systems. Here we use publicly available transcriptomic, copy number alteration and mutation profiling datasets from pancreatic cancer patients together with data on disease outcomes to show that the three major pancreatic cancer subtypes each display distinctive aberrations in cell signaling and metabolic pathways. Importantly, patients afflicted with these different pancreatic cancer subtypes also exhibit distinctive survival profiles. Within these patients, we find that dysregulation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways, and p53 mediated disruptions of cell cycle processes are apparently drivers of disease. Further, we identify for the first time the molecular perturbations of signalling networks that are likely the primary causes of oncogenesis in each of the three pancreatic cancer subtypes.

SUBMITTER: Sinkala M

PROVIDER: S-EPMC6044387 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Integrative landscape of dysregulated signaling pathways of clinically distinct pancreatic cancer subtypes.

Sinkala Musalula M Mulder Nicola N Martin Darren Patrick DP

Oncotarget 20180626 49

Despite modern therapeutic advances, the survival prospects of pancreatic cancer patients have remained poor. Besides being highly metastatic, pancreatic cancer is challenging to treat because it is caused by a heterogeneous array of somatic mutations that impact a variety of signaling pathways and cellular regulatory systems. Here we use publicly available transcriptomic, copy number alteration and mutation profiling datasets from pancreatic cancer patients together with data on disease outcome ...[more]

PMID: 30018740

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Project description:Colorectal cancer (CRC) is the third most frequently detected type of cancer, and the second most common cause of cancer‑related mortality globally. The American Cancer Society predicted that approximately 147,950 individuals would be diagnosed with CRC, out of which 53,200 individuals would succumb to the disease in the USA alone in 2020. CRC‑related mortality ranks third among both males and females in the USA. CRC arises from 3 major pathways: i) The adenoma‑carcinoma sequence; ii) serrated pathway; and iii) the inflammatory pathway. The majority of cases of CRC are sporadic and result from risk factors, such as a sedentary lifestyle, obesity, processed diets, alcohol consumption and smoking. CRC is also a common preventable cancer. With widespread CRC screening, the incidence and mortality from CRC have decreased in developed countries. However, over the past few decades, CRC cases and mortality have been on the rise in young adults (age, <50 years). In addition, CRC cases are increasing in developing countries with a low gross domestic product (GDP) due to lifestyle changes. CRC is an etiologically heterogeneous disease classified by tumor location and alterations in global gene expression. Accumulating genetic and epigenetic perturbations and aberrations over time in tumor suppressor genes, oncogenes and DNA mismatch repair genes could be a precursor to the onset of colorectal cancer. CRC can be divided as sporadic, familial, and inherited depending on the origin of the mutation. Germline mutations in APC and MLH1 have been proven to play an etiological role, resulting in the predisposition of individuals to CRC. Genetic alterations cause the dysregulation of signaling pathways leading to drug resistance, the inhibition of apoptosis and the induction of proliferation, invasion and migration, resulting in CRC development and metastasis. Timely detection and effective precision therapies based on the present knowledge of CRC is essential for successful treatment and patient survival. The present review presents the CRC incidence, risk factors, dysregulated signaling pathways and targeted therapies.

Dataset Information

Integrative landscape of dysregulated signaling pathways of clinically distinct pancreatic cancer subtypes.

Publications

Integrative landscape of dysregulated signaling pathways of clinically distinct pancreatic cancer subtypes.

Similar Datasets

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