Tumor-producing Myc protein can be targeted at last

Share this article:

The surprising discovery of an important functional link between the Myc oncogene and a regulator of protein synthesis control has finally provided scientists with a way to attack Myc-driven hematologic cancers.

Myc is one of the most commonly deregulated oncogenes in human cancer, acting somewhat as a master switch within cells to foster their uncontrolled growth. This tumor-driving protein has been previously impossible to target with drugs.

Now, however, a team led by Davide Ruggero, PhD, and Kevan Shokat, PhD, both of the University of California–San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center (San Francisco, California), has uncovered a biochemical link between Myc and mammalian target of rapamycin (mTOR)–dependent phosphorylation of a protein known as 4EBP1. 4EPP1 is a master regulator of protein production, and not only does Myc drive protein production, but Myc-driven cancer cells become dependent on this ability to make abnormal amounts of protein. When present in tumors, both abnormal Myc and abnormal mTOR are known to be able to “rev up” protein production and foster cell growth, according to a statement from UCSF.

As the researchers recounted in Proceedings of the National Academy of Sciences of the United States of America (PNAS), mTOR-dependent phosphorylation of 4EBP1 is required for cancer cell survival in Myc-dependent tumor initiation and maintenance. They further learned that an mTOR inhibitor capable of blocking 4EBP1 phosphorylation has remarkable therapeutic efficacy in Myc-driven hematologic cancers: The experimental drug, called MLN0128, stopped tumor growth in mouse models of Myc-driven lymphoma and multiple myeloma. (Currently available mTOR inhibitors do not inhibit mTOR's ability to target 4EBP1, noted the UCSF statement.)

“This is a unique therapeutic approach to make MYC ‘druggable' in the clinic,” Shokat commented in the UCSF statement.

Share this article:
You must be a registered member of ONA to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Genitourinary Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Rare Cancers Regimens
Skin Cancer Regimens Drugs