Platelet-derived Growth Factor Primes Cancer-associated Fibroblasts for Apoptosis

Rizvi, Sumera; Mertens, Joachim C.; Bronk, Steven F.; Hirsova, Petra; Dai, Haiming; Roberts, Lewis R.; Kaufmann, Scott H.; Gores, Gregory J.

doi:10.1074/jbc.m114.563064

Cited by 47 publications

(42 citation statements)

References 51 publications

(57 reference statements)

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“…Besides the involvement of several signalling pathways with potential therapeutic aim, which impact CAFs' role in tumour progression, CAFs themselves have been highlighted as a target. In two recent studies, BH3 mimetics were demonstrated in animal models to reduce the tumour burden by effectively targeting the stroma [95,96].…”

Section: Biliary Tumour Microenvironmentmentioning

confidence: 99%

Impact of microenvironment and stem-like plasticity in cholangiocarcinoma: Molecular networks and biological concepts

Raggi

Invernizzi

Andersen

2015

Journal of Hepatology

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Clinical complexity, anatomic diversity and molecular heterogeneity of cholangiocarcinoma (CCA) represent a major challenge in the assessment of effective targeted therapies. Molecular and cellular mechanisms underlying the diversity of CCA growth patterns remain a key issue of clinical concern. Crucial questions comprise the nature of the CCA-origin, the initial target for cellular transformation as well as the relationship with the cancer stem cells (CSC) concept. Additionally, since CCA often develops in the context of an inflammatory milieu (cirrhosis and cholangitis), the stromal compartment or tumour microenvironment (TME) likely promotes initiation and progression of this malignancy, contributing to its heterogeneity. This review will emphasize the dynamic interplay between stem-like intrinsic and TME-extrinsic pathways, which may represent novel options for multi-targeted therapies in CCA.

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Section: Biliary Tumour Microenvironmentmentioning

confidence: 99%

Impact of microenvironment and stem-like plasticity in cholangiocarcinoma: Molecular networks and biological concepts

Raggi

Invernizzi

Andersen

2015

Journal of Hepatology

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“…BH3 mimetics CAFs are primed for cell death as a result of heightened PDGF signaling (Rizvi et al 2014). Cell death Figure 3.…”

Section: Potential Therapies Aimed At Eliminating Cafsmentioning

confidence: 99%

“…can be triggered by BH3 mimetics, an approach that can be exploited for therapeutic purposes. Given the addiction of CAFs for PDGF signaling, Rizvi et al (2014) reasoned that PDGF isomers (that are abundantly expressed in desmoplastic stroma of cholangiocarcinoma) could specifically prime CAFs for targeted BH3 mimetic-driven cell death.…”

Section: Potential Therapies Aimed At Eliminating Cafsmentioning

confidence: 99%

Carcinoma-associated fibroblasts: orchestrating the composition of malignancy

2016

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The tumor stroma is no longer seen solely as physical support for mutated epithelial cells but as an important modulator and even a driver of tumorigenicity. Within the tumor stromal milieu, heterogeneous populations of fibroblast-like cells, collectively termed carcinoma-associated fibroblasts (CAFs), are key players in the multicellular, stromal-dependent alterations that contribute to malignant initiation and progression. This review focuses on novel insights into the contributions of CAFs to disease progression, emergent events leading to the generation of CAFs, identification of CAF-specific biomarkers predictive of disease outcome, and recent therapeutic approaches aimed at blunting or reverting detrimental protumorigenic phenotypes associated with CAFs.

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“…CCA is also a highly desmoplastic cancer with a rich stroma characterized by cancer associated fibroblasts (CAF). Preclinical data suggest that CAF are susceptible to a class of drugs termed BH3 mimetics and that targeting CAF with these agents may have an anti-tumor effect in CCA (30).…”

Section: Cca Genetics and Cancer Detectionmentioning

confidence: 99%

Advances in cholangiocarcinoma research: report from the third Cholangiocarcinoma Foundation Annual Conference

Abou‐Alfa

Andersen

Chapman

et al. 2016

J. Gastrointest. Oncol.

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Platelet-derived Growth Factor Primes Cancer-associated Fibroblasts for Apoptosis

Cited by 47 publications

References 51 publications

Impact of microenvironment and stem-like plasticity in cholangiocarcinoma: Molecular networks and biological concepts

Impact of microenvironment and stem-like plasticity in cholangiocarcinoma: Molecular networks and biological concepts

Carcinoma-associated fibroblasts: orchestrating the composition of malignancy

Advances in cholangiocarcinoma research: report from the third Cholangiocarcinoma Foundation Annual Conference

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