ErbB3 inhibitory surrobodies inhibit tumor cell proliferation in vitro and in vivo

Molecular Cancer Therapeutics
Pamela K ForemanRamesh R Bhatt

Abstract

ErbB3 is an important regulator of tumorigenesis and is implicated in development of resistance to several currently used oncology drugs. We have identified ErbB3 inhibitors based on a novel biologic scaffold termed a surrobody. Two of these inhibitors appear to work by a previously unrecognized mechanism of action. As a consequence, they not only inhibited cell proliferation and intracellular signaling driven by stimulation with the ErbB3 ligand neuregulin (NRG), but also inhibited signaling and proliferation that was driven by overexpression of ErbB2 in the absence of ligand stimulation. In addition, the surrobodies inhibited tumor growth in vivo in both ErbB2-overexpressing and nonoverexpressing cells. In ErbB2-overexpressing cells, both of the anti-ErbB3 surrobodies significantly augmented the activities of trastuzumab, lapatinib, and GDC-0941, agents that inhibit cell proliferation by different mechanisms. Moreover, although NRG diminished the efficacy of these agents, when they were combined with anti-ErbB3 surrobodies the affect of NRG was abrogated. In this capacity, the anti-ErbB3 surrobodies were more effective than the ErbB2/ErbB3 dimerization inhibitory antibody pertuzumab. Despite the fact that these surrobodies ap...Continue Reading

References

May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·P CarterH M Shepard
Jul 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Thomas HolbroNancy E Hynes
Apr 20, 2004·Cancer Cell·Matthew C FranklinMark X Sliwkowski
Dec 22, 2004·The Journal of Biological Chemistry·Kian KaniRalf Landgraf
Feb 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey A EngelmanLewis C Cantley
Sep 10, 2005·Cancer Immunology, Immunotherapy : CII·Camellia W AdamsMark X Sliwkowski
Jul 18, 2008·Cancer Research·Si Tuen Lee-HoeflichHoward M Stern
Jul 31, 2008·Proceedings of the National Academy of Sciences of the United States of America·Li XuRichard A Lerner
May 21, 2009·Science Signaling·Ingo LangeReinhold Penner
Jun 11, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Evelyn YaoKlaus P Hoeflich
Mar 11, 2010·Cancer Research·Birgit SchoeberlKwok-Kin Wong
Jun 25, 2010·Science Translational Medicine·Carolyn Clancy, Francis S Collins
Mar 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Joan T GarrettCarlos L Arteaga
Mar 26, 2011·Journal of the National Cancer Institute·Renee Twombly
Sep 29, 2011·Cellular Signalling·Lene Melsæther GrøvdalBo van Deurs
Oct 1, 2011·Breast Cancer Research and Treatment·Eugene R Ahn, Charles L Vogel
Dec 14, 2011·The New England Journal of Medicine·José BaselgaUNKNOWN CLEOPATRA Study Group

❮ Previous
Next ❯

Citations

Jun 4, 2013·Cellular and Molecular Life Sciences : CMLS·Johan NilvebrantSophia Hober
Jun 3, 2014·Molecular Cancer·Jian MaBolin Liu
Jan 11, 2017·MAbs·Ulrich Brinkmann, Roland E Kontermann
Apr 2, 2019·Biological Procedures Online·Xiaolong LiuBolin Liu
Feb 15, 2015·Experimental Biology and Medicine·Izabela BaryłaAndrzej K Bednarek
Oct 31, 2015·Molecular Cancer Therapeutics·Snezana MilutinovicJohn C Reed

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.