We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Suppression of a Specific Kinase Blocks Growth of Dependent Tumors

By LabMedica International staff writers
Posted on 20 Dec 2018
Print article
Image: A model of the active site of the kinase GSK-3 (glycogen synthase kinase 3) (Photo courtesy of Wikimedia Commons).
Image: A model of the active site of the kinase GSK-3 (glycogen synthase kinase 3) (Photo courtesy of Wikimedia Commons).
A recent paper revealed that the enzyme glycogen synthase kinase 3 (GSK3) was required for the in vitro and in vivo growth and survival of human mutant KRas-dependent tumors but was dispensable for mutant KRas-independent tumors.

Approximately 20% of all human cancers have mutations in the KRas (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) gene. These KRas-mutant cancers are among the most difficult to treat due to their resistance to chemotherapy.

Since targeting KRas directly has proven difficult, identifying vulnerabilities specific for mutant KRas tumors is an important alternative approach. Toward this end, investigators at the Moffit Cancer Center (Tampa, FL, USA) sought to identify kinases and their corresponding pathways that were required by mutant KRas tumors in order to induce malignant transformation and to target such pathways for cancer therapy.

They reported in the December 4, 2018, online edition of the journal Nature Communications that the kinase GSK3 was necessary for survival of a KRas-dependent cancer cell line, and that suppression of GSK3 inhibited tumor growth by increasing the levels of beta-catenin, a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcription, and c-Myc, a regulator of genes and proto-oncogenes that code for transcription factors. Inhibiting phosphorylation of the GSK3 substrates c-Myc and beta-catenin and their subsequent upregulation contributed to the antitumor activity of GSK3 inhibition.

The investigators showed that GSK3 chemical or genetic blockade inhibited the growth in mice of mutant KRas primary and metastatic patient-derived xenografts from pancreatic cancer patients who had progressed despite chemo- and radiation therapies. This discovery has opened new avenues to target mutant KRas-dependent cancers.

“This study discovered a novel vulnerability in mutant KRas-addicted human cancers. We have uncovered an essential link between GSK3 activity and mutant KRas dependency that is highly relevant in many aggressive and end-stage cancers. This discovery opens new avenues to target mutant KRas-addicted cancers,” said senior author Dr. Said Sebti, a senior member of the drug discovery department at Moffit Cancer Center.

Related Links:
Moffit Cancer Center

Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
One Step HbA1c Measuring System
GREENCARE A1c
POCT Fluorescent Immunoassay Analyzer
FIA Go
New
Gold Member
Systemic Autoimmune Testing Assay
BioPlex 2200 ANA Screen with MDSS

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: MOF materials efficiently enrich cfDNA and cfRNA in blood through simple operational process (Photo courtesy of Science China Press)

Blood Circulating Nucleic Acid Enrichment Technique Enables Non-Invasive Liver Cancer Diagnosis

The ability to diagnose diseases early can significantly enhance the effectiveness of clinical treatments and improve survival rates. One promising approach for non-invasive early diagnosis is the use... Read more

Hematology

view channel
Image: The low-cost portable device rapidly identifies chemotherapy patients at risk of sepsis (Photo courtesy of 52North Health)

POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy

Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more

Pathology

view channel
Image: The OvaCis Rapid Test discriminates benign from malignant epithelial ovarian cysts (Photo courtesy of INEX)

Intra-Operative POC Device Distinguishes Between Benign and Malignant Ovarian Cysts within 15 Minutes

Ovarian cysts represent a significant health issue for women globally, with up to 10% experiencing this condition at some point in their lives. These cysts form when fluid collects within a thin membrane... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.