Pancreatic cancer

Modulation of kras, micrornas, and intercellular communication in the setting of tumor heterogeneity

Research output: Contribution to journalReview article

14 Citations (Scopus)

Abstract

Supplemental digital content is available in the text. ABSTRACT: Mutations in KRAS - one of the ras family of oncogenes, encoding a GTPase critical to intracellular signal transduction - are more prevalent (80%-95%) in pancreatic cancer than in any other malignancy. There is increasing evidence that stromal cells - including pancreatic stellate cells - play a vital role in development and progression of pancreatic carcinomas. Advances in understanding the underlying biology of tumor-stroma interactions and tumor heterogeneity are critical to guiding rational approaches to designing treatments tailored to targeting KRAS in the stroma-rich microenvironment. Areas of interest in creating novel approaches to therapy include elucidating interactions of KRAS with microRNAs, the role of intratumoral hypoxia, and exploration of diverse modes of intercellular propagation of signals that stimulate malignant invasion and metastasis. This article provides an overview and state-of-the-art update of knowledge regarding pancreatic tumor biology, with a special focus on pancreatic tumor heterogeneity, the role of microRNA-mediated and hypoxic alterations in gene expression and interactions with KRAS, intercellular communication and trafficking, and progress in understanding KRAS as a potential target for pancreatic cancer therapy.

Original languageEnglish (US)
Pages (from-to)1218-1226
Number of pages9
JournalPancreas
Volume42
Issue number8
DOIs
StatePublished - Nov 1 2013

Fingerprint

MicroRNAs
Pancreatic Neoplasms
Neoplasms
Pancreatic Stellate Cells
ras Genes
GTP Phosphohydrolases
Stromal Cells
Signal Transduction
Neoplasm Metastasis
Gene Expression
Mutation
Therapeutics

Keywords

  • hypoxia
  • intercellular communication
  • KRAS
  • microRNAs
  • pancreatic cancer
  • tunneling nanotubes

Cite this

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title = "Pancreatic cancer: Modulation of kras, micrornas, and intercellular communication in the setting of tumor heterogeneity",
abstract = "Supplemental digital content is available in the text. ABSTRACT: Mutations in KRAS - one of the ras family of oncogenes, encoding a GTPase critical to intracellular signal transduction - are more prevalent (80{\%}-95{\%}) in pancreatic cancer than in any other malignancy. There is increasing evidence that stromal cells - including pancreatic stellate cells - play a vital role in development and progression of pancreatic carcinomas. Advances in understanding the underlying biology of tumor-stroma interactions and tumor heterogeneity are critical to guiding rational approaches to designing treatments tailored to targeting KRAS in the stroma-rich microenvironment. Areas of interest in creating novel approaches to therapy include elucidating interactions of KRAS with microRNAs, the role of intratumoral hypoxia, and exploration of diverse modes of intercellular propagation of signals that stimulate malignant invasion and metastasis. This article provides an overview and state-of-the-art update of knowledge regarding pancreatic tumor biology, with a special focus on pancreatic tumor heterogeneity, the role of microRNA-mediated and hypoxic alterations in gene expression and interactions with KRAS, intercellular communication and trafficking, and progress in understanding KRAS as a potential target for pancreatic cancer therapy.",
keywords = "hypoxia, intercellular communication, KRAS, microRNAs, pancreatic cancer, tunneling nanotubes",
author = "Emil Lou and Subree Subramanian and Steer, {Clifford J}",
year = "2013",
month = "11",
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doi = "10.1097/MPA.0000000000000007",
language = "English (US)",
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}

TY - JOUR

T1 - Pancreatic cancer

T2 - Modulation of kras, micrornas, and intercellular communication in the setting of tumor heterogeneity

AU - Lou, Emil

AU - Subramanian, Subree

AU - Steer, Clifford J

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Supplemental digital content is available in the text. ABSTRACT: Mutations in KRAS - one of the ras family of oncogenes, encoding a GTPase critical to intracellular signal transduction - are more prevalent (80%-95%) in pancreatic cancer than in any other malignancy. There is increasing evidence that stromal cells - including pancreatic stellate cells - play a vital role in development and progression of pancreatic carcinomas. Advances in understanding the underlying biology of tumor-stroma interactions and tumor heterogeneity are critical to guiding rational approaches to designing treatments tailored to targeting KRAS in the stroma-rich microenvironment. Areas of interest in creating novel approaches to therapy include elucidating interactions of KRAS with microRNAs, the role of intratumoral hypoxia, and exploration of diverse modes of intercellular propagation of signals that stimulate malignant invasion and metastasis. This article provides an overview and state-of-the-art update of knowledge regarding pancreatic tumor biology, with a special focus on pancreatic tumor heterogeneity, the role of microRNA-mediated and hypoxic alterations in gene expression and interactions with KRAS, intercellular communication and trafficking, and progress in understanding KRAS as a potential target for pancreatic cancer therapy.

AB - Supplemental digital content is available in the text. ABSTRACT: Mutations in KRAS - one of the ras family of oncogenes, encoding a GTPase critical to intracellular signal transduction - are more prevalent (80%-95%) in pancreatic cancer than in any other malignancy. There is increasing evidence that stromal cells - including pancreatic stellate cells - play a vital role in development and progression of pancreatic carcinomas. Advances in understanding the underlying biology of tumor-stroma interactions and tumor heterogeneity are critical to guiding rational approaches to designing treatments tailored to targeting KRAS in the stroma-rich microenvironment. Areas of interest in creating novel approaches to therapy include elucidating interactions of KRAS with microRNAs, the role of intratumoral hypoxia, and exploration of diverse modes of intercellular propagation of signals that stimulate malignant invasion and metastasis. This article provides an overview and state-of-the-art update of knowledge regarding pancreatic tumor biology, with a special focus on pancreatic tumor heterogeneity, the role of microRNA-mediated and hypoxic alterations in gene expression and interactions with KRAS, intercellular communication and trafficking, and progress in understanding KRAS as a potential target for pancreatic cancer therapy.

KW - hypoxia

KW - intercellular communication

KW - KRAS

KW - microRNAs

KW - pancreatic cancer

KW - tunneling nanotubes

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