XL-184 (Cabozantinib) goes 12-for-12 in colorectal cancer explants

April 8, 2013, University of Colorado Denver

The novel c-MET and VEGFR2 inhibitor, XL-184 (Cabozantinib), resulted in a significant decrease in tumor growth in 12 out of 12 colorectal cancer (CRC) patient-derived explants, with 8 of the explants exhibiting stable disease. The results of this preclinical work are presented at the AACR Annual Meeting 2013.

"With molecularly targeted agents, we typically see 3 or 4 CRC explant models with a significant decrease in tumor growth. Here we have a drug that was active in every explant we tested. It's really exciting," says John Arcaroli, PhD, investigator at the University of Colorado and assistant professor in the Division of at the University of Colorado School of Medicine, the study's senior author. Dr. Arcaroli works with Wells Messersmith, MD, co-leader of the CU Cancer Center Developmental Therapeutics Program to develop and test for the treatment of gastrointestinal malignancies.

This drug appears to work by inhibiting angiogenesis – the growth of new blood vessels that tumor tissues need to supply themselves with nutrients. Unlike other drugs that target angiogenesis, XL-184 targets not only the primary driver of angiogenesis, the VEGFR2 signaling pathway, but also targets c-Met, a pathway that is important for survival of tumor cells.

"Other studies have shown that anti-VEGF therapy decreases angiogenesis, but also promotes tumor and metastasis that is dependent on the c-MET signaling pathway," Arcaroli says. "This drug inhibits both – the formation of blood vessels and a primary escape mechanism whereby survive. This two-target approach may be the reason we're seeing very potent effects with this agent."

The group, which also includes members from the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center and from Harvard Medical School, is now investigating the mechanisms by which the compound reduces . The group also plans additional explant testing in order to identify predictive biomarkers of sensitivity or resistance to XL-184. In combination, this work will likely lead to a Phase II biomarker-driven clinical trial of the drug in patients with metastatic colorectal cancer.

Explore further: Combination therapy shows potent tumor growth inhibition in preclinical studies

Related Stories

Combination therapy shows potent tumor growth inhibition in preclinical studies

November 13, 2011
Combining the investigational agents REGN910 and aflibercept yielded statistically significant improvements in antitumor effects in animal models compared with either agent alone, according to results presented at the AACR-NCI-EORTC ...

Combination treatment may improve survival of breast cancer patients with brain metastases

November 1, 2012
Adding an angiogenesis inhibitor to treatment with a HER2-inhibiting drug could improve outcomes for patients with HER2-positive breast cancer who develop brain metastases. In their report published online in PNAS Plus, Massachusetts ...

Recommended for you

Workouts may boost life span after breast cancer

January 22, 2018
(HealthDay)—Longer survival after breast cancer may be as simple as staying fit, new research shows.

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

Cancer patients who tell their life story find more peace, less depression

January 22, 2018
Fifteen years ago, University of Wisconsin–Madison researcher Meg Wise began interviewing cancer patients nearing the end of life about how they were living with their diagnosis. She was surprised to find that many asked ...

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.