Open Close
Reference
Citation
Bangi, E., Ang, C., Smibert, P., Uzilov, A.V., Teague, A.G., Antipin, Y., Chen, R., Hecht, C., Gruszczynski, N., Yon, W.J., Malyshev, D., Laspina, D., Selkridge, I., Rainey, H., Moe, A.S., Lau, C.Y., Taik, P., Wilck, E., Bhardwaj, A., Sung, M., Kim, S., Yum, K., Sebra, R., Donovan, M., Misiukiewicz, K., Schadt, E.E., Posner, M.R., Cagan, R.L. (2019). A personalized platform identifies trametinib plus zoledronate for a patient with KRAS-mutant metastatic colorectal cancer.  Sci. Adv. 5(5): eaav6528.
FlyBase ID
FBrf0242473
Publication Type
Research paper
Abstract

Colorectal cancer remains a leading source of cancer mortality worldwide. Initial response is often followed by emergent resistance that is poorly responsive to targeted therapies, reflecting currently undruggable cancer drivers such as KRAS and overall genomic complexity. Here, we report a novel approach to developing a personalized therapy for a patient with treatment-resistant metastatic KRAS-mutant colorectal cancer. An extensive genomic analysis of the tumor's genomic landscape identified nine key drivers. A transgenic model that altered orthologs of these nine genes in the Drosophila hindgut was developed; a robotics-based screen using this platform identified trametinib plus zoledronate as a candidate treatment combination. Treating the patient led to a significant response: Target and nontarget lesions displayed a strong partial response and remained stable for 11 months. By addressing a disease's genomic complexity, this personalized approach may provide an alternative treatment option for recalcitrant disease such as KRAS-mutant colorectal cancer.

PubMed ID
PubMed Central ID
PMC6531007 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Sci. Adv.
    Title
    Science advances
    ISBN/ISSN
    2375-2548
    Data From Reference
    Genes (10)
    Human Disease Models (2)