Open AccessJupiter microtubule‐associated homolog 1 (JPT1): A predictive and pharmacodynamic biomarker of metformin response in endometrial cancers
Author(s) -
Bateman Nicholas W.,
Teng PangNing,
Hope Erica,
Hood Brian L.,
Oliver Julie,
Ao Wei,
Zhou Ming,
Wang Guisong,
Tommarello Domenic,
Wilson Katlin,
Litzy Tracy,
Conrads Kelly A.,
Hamilton Chad A.,
Darcy Kathleen M.,
Casablanca Yovanni,
Maxwell George Larry,
BaeJump Victoria,
Conrads Thomas P.
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2729
Subject(s) - metformin , medicine , pharmacodynamics , biomarker , endometrial cancer , oncology , cancer , cancer research , endocrinology , pharmacology , biology , pharmacokinetics , insulin , biochemistry
Abstract Preoperative use of metformin in obese women with endometrioid endometrial cancer (EEC) reduces tumor proliferation and inhibits the mammalian target of rapamycin pathway, though is only effective in select cases. This study sought to identify a predictive and/or pharmacodynamic proteomic signature of metformin response to tailor its pharmacologic use. Matched pre‐ and post‐metformin‐treated tumor tissues from a recently completed preoperative window trial of metformin in EEC patients (ClinicalTrials.gov: NCT01911247) were analyzed by mass spectrometry (MS)‐based proteomic and immunohistochemical analyses. Jupiter microtubule‐associated homolog 1 (JPT1) was significantly elevated in metformin responders (n = 13) vs nonresponders (n = 7), and found to decrease in abundance in metformin responders following treatment; observations that were verified by immunohistochemical staining for JPT1. Metformin response and loss of JPT1 were assessed in RL95‐2 and ACI‐181 endometrial cancer (EC) cell lines. We further identified that silencing of JPT1 abundance does not alter cellular response to metformin or basal cell proliferation, but that JPT1 abundance does decrease in response to metformin treatment in RL95‐2 and ACI‐181 EC cell lines. These data suggest that JPT1 represents a predictive and pharmacodynamic biomarker of metformin response that, if validated in larger patient populations, may enable preoperative EEC patient stratification to metformin treatment and the ability to monitor patient response.