Abstract 1753
Background
The signal transducer and activator of transcription (STAT) 3 plays a critical role in the regulation of cell growth, metastasis, and survival. STAT3 signaling is constitutively activated in various cancers including gynecological cancers. We evaluated the efficacy of a novel selective STAT3 inhibitor, YHO-1701, ex vivo and in vivo for ovarian and endometrial cancer.
Methods
An expression profile of YHO-1701 treated cells was compared with that of other STAT3 inhibitors or its upstream Janus kinase inhibitor by RNA sequencing. The downstream signaling of YHO-1701 was investigated by western blot. Patients derived primary cancer cells (PDCs) were isolated from surgical specimens or ascites cells from ovarian or endometrial cancer patients, and the growth inhibitory effect of YHO-1701 on PDCs was evaluated by standard colorimetric assays. Antitumor activity of YHO-1701 was assessed using an SKOV3 abdominal dissemination xenograft model.
Results
We investigated the specificity of YHO-1701 by pathway analysis using RNA sequencing results of the cells treated with or without each inhibitor and found YHO-1701 regulated STAT3 signaling more tightly than others did. We confirmed decreased levels of pSTAT3 S727, Survivin, and c-Myc in the cells treated with YHO-1701. A total of 41 PDCs were treated with YHO-1701 and showed a remarkable growth inhibition compared with the control group (P < 0.0007 and P < 0.0001 for ovarian and endometrial cancer cells, respectively). We tested the potential antitumor activity of orally administrated YHO-1701 in a mouse intraperitoneal dissemination model of ovarian cancer using SKOV3. We observed decreased numbers of peritoneal metastasis in mice treated with YHO-1701 compared with those treated with vehicle control (P < 0.05).
Conclusions
Our results demonstrated the efficacy of YHO-1701 for ovarian and endometrial cancer both ex vivo and in vivo through STAT3 signaling.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Yakult Honsha.
Disclosure
K. Hasegawa: Research grant / Funding (self): Yakult. K. Taniguchi: Full / Part-time employment: Yakult. A. Yoshinaga: Full / Part-time employment: Yakult. M. Tsugane: Full / Part-time employment: Yakut. All other authors have declared no conflicts of interest.
Resources from the same session
3911 - Defining a SUV decrease cut-off in PET/CT response monitoring after one cycle of preoperative breast cancer chemotherapy
Presenter: Marcin Kubeczko
Session: Poster Display session 2
Resources:
Abstract
1849 - Effect of thioredoxin 1 quantity detection to complement the mammography in breast cancer diagnosis
Presenter: Younju Lee
Session: Poster Display session 2
Resources:
Abstract
2221 - Identification of ultralow risk breast cancer patients (probable overdiagnosis)
Presenter: Salvador Gamez Casado
Session: Poster Display session 2
Resources:
Abstract
5291 - Prevalence of Vitamin D3 deficiency among women with early breast cancer receiving chemotherapy in an oncology dayward.
Presenter: Warner Finstad
Session: Poster Display session 2
Resources:
Abstract
4247 - Changes in ER pathway activity score during neoadjuvant letrozole to assess therapy response and predict disease free survival (DFS) in ER positive breast cancer patients
Presenter: Arran Turnbull
Session: Poster Display session 2
Resources:
Abstract
568 - Second primary malignancies in patients with breast cancer.
Presenter: Carlos Erasun Lecuona
Session: Poster Display session 2
Resources:
Abstract
1428 - Phase II randomized trial of neoadjuvant trastuzumab and pertuzumab (TP) with either palbociclib + letrozole (Pal+L) or paclitaxel (Pac) for elderly patients with estrogen receptor & HER2 positive (ER+/HER2+) Breast Cancer (BC) (International Breast Cancer Study Group IBCSG 55-17, TOUCH)
Presenter: Laura Biganzoli
Session: Poster Display session 2
Resources:
Abstract
1479 - Neoadjuvant HER2-targeted therapy with or without immunotherapy with pembrolizumab (neoHIP): an open label randomized phase 2 trial
Presenter: Heather McArthur
Session: Poster Display session 2
Resources:
Abstract
1481 - A randomized phase 2 study of peri-operative ipilimumab, nivolumab and cryoablation versus standard care in women with residual, early stage/resectable, triple negative breast cancer after standard-of-care neoadjuvant chemotherapy
Presenter: Heather McArthur
Session: Poster Display session 2
Resources:
Abstract
4334 - ALEXANDRA/IMpassion030: A phase 3 study of standard adjuvant chemotherapy with or without atezolizumab in early stage triple negative breast cancer.
Presenter: Michail Ignatiadis
Session: Poster Display session 2
Resources:
Abstract