�Two self-governing research groups have found that coincidental inhibition of two sign pathways resulted in substantially enhanced antineoplastic effects in mouse models of prostate and white meat cancer. In an follow commentary, Steven Grant, at Virginia Commonwealth University Health Science Center, Richmond, discusses the clinical importance of these studies and highlights some of the questions that still need to be answered.
In the first base study, Pier Paolo Pandolfi and colleagues, at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, and Memorial Sloan-Kettering Cancer Center, New York, report that tumour samples from patients with biopsy-accessible strong tumors of advanced disease treated with a drug that inhibits the mTOR signaling tract showed increased activation of the MAPK signaling footpath. Similar results were ascertained in a mouse modelling of prostate cancer undermentioned treatment with the same drug. As inhibition of the MAPK signaling nerve pathway enhanced the antitumoral personal effects of forbiddance of the mTOR sign pathway in mice transplanted with a human boob cancer cubicle line, the authors suggest that a combination therapy using drugs that object each footpath might amend the treatment of human cancers.
In the second sketch, Cory Abate-Shen and colleagues, at Columbia University College of Physicians and Surgeons, New York, and the University of Medicine & Dentistry of New Jersey, Piscataway, show that coincidental inhibition of the mTOR and MAPK signaling pathways inhibited the in vitro growth of prostate crab cell lines and the in vivo growth of prostate tumors in a mouse modeling of prostate gland cancer. This was in particular true in a manakin of highly aggressive and frequently deadly forms of the disease, which do not reply to endocrine deprivation therapy, leading the authors to suggest that this combination therapy might be peculiarly useful for treating patients with advanced, hormone-refractory prostate cancer.
TITLE: Inhibition of mTORC1 leads to MAPK nerve pathway activation through a PI3K-dependent feedback loop in human cancer
AUTHOR CONTACT:
Pier Paolo Pandolfi
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
View the PDF of this article at: https://www.the-jci.org/article.php?id=34739
RELATED MANUSCRIPT
TITLE: Targeting AKT/mTOR and ERK MAPK signal inhibits hormone-refractory prostate cancer in a preclinical mouse model
AUTHOR CONTACT:
Cory Abate-Shen
Columbia University College of Physicians and Surgeons, New York, New York, USA.
View the PDF of this article at: https://www.the-jci.org/article.php?id=34764
ACCOMPANYING COMMENTARY
TITLE: Cotargeting survival signaling pathways in cancer
AUTHOR CONTACT:
Steven Grant
Virginia Commonwealth University Health Science Center, Richmond, Virginia, USA.
View the PDF of this article at: https://www.the-jci.org/article.php?id=36898
Source: Karen Honey
Journal of Clinical Investigation
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