ABL001, a Bispecific Antibody Targeting VEGF and DLL4, with Chemotherapy, Synergistically Inhibits Tumor Progression in Xenograft Models

Yeom, Dong-Hoon; Lee, Yo-Seob; Ryu, Ilhwan; Lee, Sun-Ju; Sung, Byungje; Lee, Hanbyul; Kim, Dongin; Ahn, Jin-Hyung; Ha, Eunsin; Choi, Yong‐Soo; Lee, Sang Hoon; You, Weon‐Kyoo

doi:10.3390/ijms22010241

Cited by 29 publications

(15 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, the Notch signaling inhibitor LY3039478 has been demonstrated to be comparatively safe and active as a single agent in preliminary studies in CRC patients [ 78 ]. Interestingly, a bispecific antibody targeting VEGF and Dll4 (ABL001/NOV1501/TR009), has been recently assessed in a phase 1 clinical trial of heavy chemotherapy or targeted therapy in pre-treated cancer patients, demonstrating higher anti-cancer effects in several human cancer xenografts than the VEGF-targeting antibody (bevacizumab—similar) and the Dll4-targeting monoclonal antibody alone [ 79 ].…”

Section: Dysregulated Signaling Pathways In Colorectal Cancer: the Em...mentioning

confidence: 99%

New Insights into Bile Acids Related Signaling Pathways in the Onset of Colorectal Cancer

et al. 2022

View full text Add to dashboard Cite

Colorectal cancer (CRC) ranks as the second among the causes of tumor death worldwide, with an estimation of 1.9 million new cases in 2020 and more than 900,000 deaths. This rate might increase by 60% over the next 10 years. These data are unacceptable considering that CRC could be successfully treated if diagnosed in the early stages. A high-fat diet promotes the hepatic synthesis of bile acids (BAs) increasing their delivery to the colonic lumen and numerous scientific reports correlate BAs, especially secondary BAs, with CRC incidence. We reviewed the physicochemical and biological characteristics of BAs, focusing on the major pathways involved in CRC risk and progression. We specifically pointed out the role of BAs as signaling molecules and the tangled relationships among their nuclear and membrane receptors with the big bang of molecular and cellular events that trigger CRC occurrence.

show abstract

Section: Dysregulated Signaling Pathways In Colorectal Cancer: the Em...mentioning

confidence: 99%

New Insights into Bile Acids Related Signaling Pathways in the Onset of Colorectal Cancer

et al. 2022

View full text Add to dashboard Cite

show abstract

“…More tumor vessel regression and apoptotic tumor cell induction were observed in tumors treated with the combination therapy, which might be due to tumor vessel normalization. Overall, these findings suggest that the combination therapy of ABL001 with paclitaxel or irinotecan would be a better clinical strategy for the treatment of cancer patients [ 46 ].…”

Section: Cancer Stem Cells and Dll4 Expression In Endometrial Cancermentioning

confidence: 99%

“…Based on the outcomes of experiments, SYD985 recorded 10- to about 70-fold times more effective than TDM 1 and active against the USC unlike T-DM1.This demonstrates the heterogeneous HER2 expression. Concerning a trial (in phase I) for the HER2 expressing cancers, patients with endometrial carcinoma recorded a 39% response (phase II ongoing) [ 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ].…”

Section: Immunotherapy and Tumor-draining Lymph Nodesmentioning

confidence: 99%

The Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development

Fasoulakis

Koutras

Ntounis

et al. 2022

Cancers

View full text Add to dashboard Cite

The Notch signaling pathway regulates the development of embryonic and tissue homeostasis of various types of cells. It also controls cell proliferation, variation, fate and cell death because it emits short-range messages to nearby cells. The pathway plays an important role in the pathophysiology of various malignancies, controlling cancer creation. It also limits cancer development by adjusting preserved angiogenesis and cellular programs. One of the Notch signaling ligands (in mammals) is Delta-like ligand 4 (Dll4), which plays a significant role in the overall malignancies’ advancement. Particularly, sequencing Notch gene mutations, including those of Dll4, have been detected in many types of cancers portraying information on the growth of particular gynecological types of tumors. The current research article examines the background theory that implies the ability of Dll4 in the development of endometrial and other cancer types, and the probable therapeutic results of Dll4 inhibition.

show abstract

“…Since growing evidence is unraveling the relationship between angiogenesis and Dll4/Notch signaling, Dll4 has emerged as a promising target [252][253][254] . Indeed, over the years, several studies documented that Dll4 inhibition has proved extremely fruitful to overcome anti-VEGF resistance due to the augmented observed effects when combined with anti-VEGF inhibitors [255][256][257] .…”

Section: Disrupting Notch Signaling In Tumor Vasculature To Overcome Anti-angiogenic Therapy Resistance and Favor Chemotherapymentioning

confidence: 99%

Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Giuli¹,

Mancusi²,

Giuliani³

et al. 2021

CDR

View full text Add to dashboard Cite

Drug resistance is one of the main challenges in cancer therapy, including in the treatment of female-specific malignancies, which account for more than 60% of cancer cases among women. Therefore, elucidating the underlying molecular mechanisms is an urgent need in gynecological cancers to foster novel therapeutic approaches. Notably, Notch signaling, including either receptors or ligands, has emerged as a promising candidate given its multifaceted role in almost all of the hallmarks of cancer. Concerning the connection between Notch pathway and drug resistance in the afore-mentioned tumor contexts, several studies focused on the Notchdependent regulation of the cancer stem cell (CSC) subpopulation or the induction of the epithelial-tomesenchymal transition (EMT), both features implicated in either intrinsic or acquired resistance. Indeed, the present review provides an up-to-date overview of the published results on Notch signaling and EMT-or CSCdriven drug resistance. Moreover, other drug resistance-related mechanisms are examined such as the involvement of the Notch pathway in drug efflux and tumor microenvironment. Collectively, there is a long way to go before every facet will be fully understood; nevertheless, some small pieces are falling neatly into place. Overall, the main aim of this review is to provide strong evidence in support of Notch signaling inhibition as an effective strategy to evade or reverse resistance in female-specific cancers.

show abstract

ABL001, a Bispecific Antibody Targeting VEGF and DLL4, with Chemotherapy, Synergistically Inhibits Tumor Progression in Xenograft Models

Cited by 29 publications

References 42 publications

New Insights into Bile Acids Related Signaling Pathways in the Onset of Colorectal Cancer

New Insights into Bile Acids Related Signaling Pathways in the Onset of Colorectal Cancer

The Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development

Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Contact Info

Product

Resources

About