Abstract 1317
Background
The Jmjc-domain-containing protein 6 (JMJD6) is a member of JmjC oxygenases that contain both arginine demethylase and lysine hydroxylase activities. Overexpression of JMJD6 has been reported to be associated with the development of various types of cancers, such as breast, lung, liver, and colon cancer. The present study aimed to explore the inhibitory effect of the small-molecule JMJD6 inhibitor named WL8 obtained by virtual screening on the progression of colorectal cancer.
Methods
WL8 was administered to a mouse bearing xenografts of human colorectal cancer tissue, once every 7 days for 3 times. We analyzed the response of tumors from three patients to the JMJD6 inhibitor (11.5mg/kg, intrapertoneally, i.p.), and to FOLFOX (oxaliplatin 12mg/kg, calcium levifolinate 30mg/kg, 5-fluorouracil 55mg/kg, i.p.) or FOLFIRI (irinotecan 40mg/kg, calcium levifolinate 30mg/kg, 5-fluorouracil 55mg/kg, i.p.), as well as to combined usage of JMJD6 inhibitor and FOLFOX or FOLFIRI in PDX models by recording the tumors sizes every 3 or 4 days for 7 times. The differences between groups were analyzed using one-way ANOVA. (i.p. stands for intraperitoneal.).
Results
Compared with FOLFOX or FOLFIRI, WL8 inhibited tumor growth more effectively in the PDX models of three patients (One patient’s partial results are shown in the table). Combinatorial therapies using both JMJD6 and FOLFOX (or FOLFIRI) could further reduced the tumour size.Table: 632P
Group | 8 Days | 15 Days | 22 Days |
---|---|---|---|
Control | 1.8075±0.3950 $^@ | 2.5706±0.2900 #%$^@ | 2.6834±0.0416 #%$^@ |
FOLFOX | 1.4184±0.2067 | 1.3639±0.2381 *@ | 1.3867±0.4155 *^@ |
FOLFIRI | 1.4712±0.1568 | 1.3894±0.4543 *@ | 1.7474±0.0705 *$^@ |
WL8 | 0.9656±0.4456 * | 1.1069±0.4376 * | 1.1655±0.2884 *%^@ |
WL8+ FOLFOX | 0.7125±0.0410 *#% | 0.7767±0.4359 * | 0.4833±0.0503 *#%$ |
WL8+ FOLFIRI | 1.0325±0.3903* | 0.6367±0.1436 *#% | 0.3900±0.0265 *#%$ |
Relative tumor volumn (on days after first administration, notes: P values are indicated with symbols as follows, * P<0.05 v.s. ctrl; # P<0.05 v.s. FOLFOX; % P<0.05 v.s. FOFIRI; $ P<0.05 v.s. WL8; ^ P<0.05 v.s. WL8+FOLFOX; @ P<0.05 v.s. WL8+FOLFIRI)
Conclusions
We found an small-molecule inhibitor of JMJD6 with impressive therapeutic effects on colorectal cancer in pre-clinical study.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The First Affiliated Hospital of Xiamen University.
Funding
National Natural Science Foundation of China, Fujian Provincial Department of Science and Technology, Fujian Provincial Health and Family Planning Commission Foundation of Youth Scientific Research Project, Xiamen Science and Technology Bureau Foundation of Science and Technology Project for the Benefit of the People.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3034 - Efficacy and safety of neoadjuvant chemotherapy plus trastuzumab and pertuzumab in non-metastatic HER2-positive breast cancer in real life: NEOPEARL STUDY
Presenter: Maria Agnese Fabbri
Session: Poster Display session 2
Resources:
Abstract
4772 - Real world comparison of the impact of adjuvant capecitabine in women with high-risk triple-negative breast cancer after neoadjuvant chemotherapy
Presenter: Maysa Vilbert
Session: Poster Display session 2
Resources:
Abstract
5627 - Influence of age on the indication of adjuvant chemotherapy in early breast cancer using Oncotype DX. An analysis of 240 patients treated in the Institut Catala d’Oncologia (ICO) hospitals
Presenter: Sabela Recalde
Session: Poster Display session 2
Resources:
Abstract
3917 - Impact of delayed neoadjuvant systemic chemotherapy on survival among breast cancer patients
Presenter: Mariana Chavez Mac Gregor
Session: Poster Display session 2
Resources:
Abstract
2246 - Clinical Confirmation of Higher Exposure to Niraparib in Tumor vs Plasma in Patients With Breast Cancer
Presenter: Laura Spring
Session: Poster Display session 2
Resources:
Abstract
581 - The rationale for the effectiveness of systemic treatment of breast cancer depending on the body weight index
Presenter: Mohammad Hojouj
Session: Poster Display session 2
Resources:
Abstract
5327 - Response to neoadjuvant chemotherapy in HER2 non-overexpressing breast cancer subtypes
Presenter: Silvia Mihaela Ilie
Session: Poster Display session 2
Resources:
Abstract
3613 - Pre-specified interim analysis of the SAFE trial (NCT2236806): a 4-arm randomized, double-blind, controlled study evaluating the efficacy and safety of cardiotoxicity prevention in non-metastatic breast cancer patients treated with anthracyclines with or without trastuzumab.
Presenter: Lorenzo Livi
Session: Poster Display session 2
Resources:
Abstract
3736 - Safety of hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: a multi-center comparative study.
Presenter: Icro Meattini
Session: Poster Display session 2
Resources:
Abstract
5085 - Usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab
Presenter: Isabel Blancas López-Barajas
Session: Poster Display session 2
Resources:
Abstract