Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling

By Eric G. Bluemn, Ilsa M Coleman, Jared M. Lucas, R. Coleman, S. Hernández-López, Robin G. Tharakan, D. Bianchi-Frias, R. Dumpit, A. Kaipainen, Alexandra Corella and 17 more. Cancer Cell, 2017

652 citations recorded by the source corpus.

SUMMARY Androgen receptor (AR) signaling is a distinctive feature of prostate carcinoma (PC) and represents the major therapeutic target for treating metastatic prostate cancer (mPC). Though highly effective, AR antagonism can produce tumors that bypass a functional requirement for AR, often through neuroendocrine (NE) transdifferentiation. Through the molecular assessment of mPCs over two decades, we find a phenotypic shift has occurred in mPC with the emergence of an AR-null NE-null phenotype. These “double-negative” PCs are notable for elevated FGF and MAPK pathway activity, which can bypass AR dependence. Pharmacological inhibitors of MAPK or FGFR repressed the growth of double-negative PCs in vitro and in vivo. Our results indicate that FGF/MAPK blockade may be particularly efficacious against mPCs with an AR-null phenotype.

Subfields: Cell Biology, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/0642bf8447b92adb606d01a10dfe446cbb4336bf

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In Molecular Biology

1. Mark A. Rubin
2. Nikolaus Schultz
3. Arul M. Chinnaiyan
4. C. Sawyers
5. E. Scholar
6. A. Arora

In Pulmonary and Respiratory Medicine

1. Arul M. Chinnaiyan
2. C. Sawyers
3. Mark A. Rubin
4. M. Hallek

Citations in the corpus

• Genomic correlates of clinical outcome in advanced prostate cancer (2019, methodology): “RNA-based expression signatures have been proposed as a potential alternative diagnostic strategy to define this distinct clinical state (8, 30, 31).”