Combined aromatase, CDK4/6 and PI3K blockade using letrozole/abemaciclib/LY3023414 in endometrial cancer

Several lines of preclinical evidence indicate that combining PI3K and CDK4/6 inhibitors may further enhance the efficacy of hormonal therapy by overcoming de novo and acquired resistance to PI3K and CDK4/6 blockade. We evaluated the combination of abemaciclib, letrozole and LY3023414 (an orally ava...

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Main Authors: Panagiotis A. Konstantinopoulos (Author), Niya Xiong (Author), Carolyn Krasner (Author), Joyce F. Liu (Author), Hannah Sawyer (Author), Madeline Polak (Author), Hope Needham (Author), Megan Geddes (Author), Lani Koppermann (Author), Meghan Shea (Author), Cesar Castro (Author), Su-Chun Cheng (Author), Ursula A. Matulonis (Author), Elizabeth K. Lee (Author)
Format: Book
Published: Elsevier, 2024-04-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Panagiotis A. Konstantinopoulos  |e author 
700 1 0 |a Niya Xiong  |e author 
700 1 0 |a Carolyn Krasner  |e author 
700 1 0 |a Joyce F. Liu  |e author 
700 1 0 |a Hannah Sawyer  |e author 
700 1 0 |a Madeline Polak  |e author 
700 1 0 |a Hope Needham  |e author 
700 1 0 |a Megan Geddes  |e author 
700 1 0 |a Lani Koppermann  |e author 
700 1 0 |a Meghan Shea  |e author 
700 1 0 |a Cesar Castro  |e author 
700 1 0 |a Su-Chun Cheng  |e author 
700 1 0 |a Ursula A. Matulonis  |e author 
700 1 0 |a Elizabeth K. Lee  |e author 
245 0 0 |a Combined aromatase, CDK4/6 and PI3K blockade using letrozole/abemaciclib/LY3023414 in endometrial cancer 
260 |b Elsevier,   |c 2024-04-01T00:00:00Z. 
500 |a 2352-5789 
500 |a 10.1016/j.gore.2024.101348 
520 |a Several lines of preclinical evidence indicate that combining PI3K and CDK4/6 inhibitors may further enhance the efficacy of hormonal therapy by overcoming de novo and acquired resistance to PI3K and CDK4/6 blockade. We evaluated the combination of abemaciclib, letrozole and LY3023414 (an orally available, selective inhibitor of the class I PI3K isoforms and mTORC1/2) in recurrent endometrial cancer (EC). This study was terminated prematurely after 5 patients initiated protocol therapy due to discontinuation of further development of LY3023414. We report our findings from these patients, including one with recurrent endometrioid EC with AKT1, CTNNB1 and ESR1 hotspot mutations who had previously progressed through letrozole/everolimus and achieved a partial response to letrozole/abemaciclib/LY3023414. 
546 |a EN 
690 |a Abemaciclib 
690 |a Aromatase inhibition 
690 |a CDK4/6 inhibition 
690 |a PI3K inhibition 
690 |a LY3023414 
690 |a Endometrial cancer 
690 |a Gynecology and obstetrics 
690 |a RG1-991 
690 |a Neoplasms. Tumors. Oncology. Including cancer and carcinogens 
690 |a RC254-282 
655 7 |a article  |2 local 
786 0 |n Gynecologic Oncology Reports, Vol 52, Iss , Pp 101348- (2024) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2352578924000274 
787 0 |n https://doaj.org/toc/2352-5789 
856 4 1 |u https://doaj.org/article/a58a03d3330d4b9d9bd8d84d99a74acc  |z Connect to this object online.