Toward personalized TGFβ inhibition for pancreatic cancer

Research output: Contribution to journalComment/debate

Abstract

Cancer can be conceptualized as arising from somatic mutations resulting in a single renegade cell escaping from the constraints of multicellularity. Thus, the era of precision medicine has led to intense focus on the cancer cell to target these mutations that result in oncogenic signaling and sustain malignancy. However, in pancreatic ductal adenocarcinoma (PDAC) there are only four abundantly common driver mutations (KRAS, CDKN2A, TP53, and SMAD4), which are not currently actionable. Thus, precision therapy for PDAC must look beyond the cancer cell. In fact, PDAC is more than a collection of renegade cells, instead representing an extensive, supportive ecosystem, having developed over several years, and consisting of numerous interactions between the cancer cells, normal mesenchymal cells, immune cells, and the dense extracellular matrix. In this issue, Huang and colleagues demonstrate how elucidation of these complex relationships within the tumor microenvironment (TME) can be exploited for therapeutic intervention in PDAC. They identify in a subset of PDAC with mutations in TGFβ signaling, that a paracrine signaling axis can be abrogated to modulate the TME and improve outcomes.

Original languageEnglish (US)
Article numbere11414
JournalEMBO Molecular Medicine
Volume11
Issue number11
DOIs
StatePublished - Nov 7 2019

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Pancreatic Neoplasms
Adenocarcinoma
Mutation
Tumor Microenvironment
Neoplasms
Paracrine Communication
Precision Medicine
Extracellular Matrix
Ecosystem
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Toward personalized TGFβ inhibition for pancreatic cancer. / Carr, Ryan M.; Fernandez-Zapico, Martin E.

In: EMBO Molecular Medicine, Vol. 11, No. 11, e11414, 07.11.2019.

Research output: Contribution to journalComment/debate

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