Drugs for DIPG: a guide for new therapies in a rare, lethal pediatric brain cancer

2019

Challenge

Diffuse intrinsic pontine glioma (DIPG) is a rare, universally lethal pediatric brain cancer that affects areas that are difficult and dangerous to access surgically. In the past, researchers had not pursued molecularly targeted therapies. In fact, there have been no advances in DIPG treatments in the past forty year.

Advance

DIPG and related forms of brain cancer are characterized by a unique mutation in the proteins that help structure DNA, which causes a weakness in the cancer cells’ metabolism. IRP researchers, led by Michele Ceribelli, Ph.D., and Craig J. Thomas, Ph.D., in collaboration with teams at Stanford University, the Dana Farber Cancer Institute, and Johns Hopkins University, screened nearly 3,000 drugs and drug combinations targeting this mutation. In addition to identifying a new target, their efforts identified several potential therapies for clinical development.

Impact

The study’s identification of a vulnerability in DIPG cancer cells has led to new theories on possible novel drug targets for the disease. The work is now catalyzing several new clinical efforts to find treatments for DIPG.

Publications

Lin GL, Wilson KM, Ceribelli M, Stanton B, Woo P, Kreimer K, Qin EY, Zhang X, Lennon J, Nagaraja S, Morris PJ, Quezada M, Gillespie SM, Duveau DY, Michalowski AM, Shinn P, Guha R, Ferrer M, Klumpp-Thomas C, McKnight C, Minhas P, Itkin Z, Raabe EH, Chen L, Andreasson K, Vitanza NA, Warren KE, Thomas CJ, Monje M. (2019). Therapeutic opportunities for diffuse midline glioma identified from high-throughput combination drug screening. Sci Trans Med. 11(519):eaaw0064.