UCLA researchers funded by Heart of the Brain play critical role in the development of new therapies for deadly brain tumors

UCLA researchers funded by Heart of the Brain play critical role in the development of new therapies for deadly brain tumors

With the generous and unwavering support of Heart of the Brain, researchers at the UCLA Brain Tumor Center have played a crucial role in developing groundbreaking therapies for hard-to-treat brain cancers.

In 2008, while sequencing malignant gliomas, researchers at UCLA identified a type of mutation called isocitrate dehydrogenase (IDH). The researchers discovered that this mutation could be found in certain types of brain cancer, including astrocytoma and oligodendroglioma.

Using this information, UCLA researchers Dr. Linda Liau and Dr. Robert Prins collaborated in the research that determined that the IDH mutation disrupts normal cellular processes by creating a unique metabolite. The accumulation of this metabolite leads to changes in gene expression patterns, which ultimately causes uncontrolled cell growth and division characteristic of glioma development.

Building from the results of Dr. Liau and Dr. Prins’s research, Dr. Timothy Cloughesy and Dr. Benjamin Ellingson, also of the UCLA Brain Tumor Center, provided principal leadership in the clinical development and trial of IDH inhibitors. These inhibitors aim to reduce the growth of cells and slow the progression of the cancer caused by the IDH mutation.

In these initial trials, the researchers determined that IDH inhibitors effectively treated patients with IDH mutant gliomas. This research laid the groundwork for the worldwide Phase 3 study INDIGO, which sought to further prove the effect of IDH inhibitors as a treatment for brain cancer.

In August 2023, the results of the INDIGO study were published in the New England Journal of Medicine with Dr. Cloughesy as senior author and one of the principal investigators. The findings indicated a dramatic improvement in the progression-free survival of patients who underwent surgery alone and allowed patients to delay other therapies such as radiation and chemotherapy.

The Neidorf Family Foundation provided the seed funding for this research during its earliest stages in 2008. Subsequent funding from the Heart of the Brain has been critical for continued groundbreaking brain tumor research at UCLA.

With these donations, the researchers of the UCLA Brain Tumor Center aim to further progress treatment using IDH inhibitors and create more hopeful futures for all brain tumor patients.


Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009 Dec 10;462(7274):739-44. doi: 10.1038/nature08617.PMID: 19935646

Mellinghoff IK, Ellingson BM, Touat M, Maher E, De La Fuente MI, Holdhoff M, Cote GM, Burris H, Janku F, Young RJ, Huang R, Jiang L, Choe S, Fan B, Yen K, Lu M, Bowden C, Steelman L, Pandya SS, Cloughesy TF, Wen PY. Ivosidenib in Isocitrate Dehydrogenase 1-Mutated Advanced Glioma. J Clin Oncol. 2020 Oct 10;38(29):3398-3406. doi: 10.1200/JCO.19.03327. Epub 2020 Jun 12.

Mellinghoff IK, Penas-Prado M, Peters KB, Burris HA 3rd, Maher EA, Janku F, Cote GM, de la Fuente MI, Clarke JL, Ellingson BM, Chun S, Young RJ, Liu H, Choe S, Lu M, Le K, Hassan I, Steelman L, Pandya SS, Cloughesy TF, Wen PY. Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial. Clin Cancer Res. 2021 Aug 15;27(16):4491-4499. doi: 10.1158/1078-0432.CCR-21-0611. Epub 2021 Jun 2.

Mellinghoff IK, Lu M, Wen PY, Taylor JW, Maher EA, Arrillaga-Romany I, Peters KB, Ellingson BM, Rosenblum MK, Chun S, Le K, Tassinari A, Choe S, Toubouti Y, Schoenfeld S, Pandya SS, Hassan I, Steelman L, Clarke JL, Cloughesy TF.  Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial. Nat Med. 2023 Mar;29(3):615-622. doi: 10.1038/s41591-022-02141-2. Epub 2023 Feb 23.

Mellinghoff IK, van den Bent MJ, Blumenthal DT, Touat M, Peters KB, Clarke J, Mendez J, Yust-Katz S, Welsh L, Mason WP, Ducray F, Umemura Y, Nabors B, Holdhoff M, Hottinger AF, Arakawa Y, Sepulveda JM, Wick W, Soffietti R, Perry JR, Giglio P, de la Fuente M, Maher EA, Schoenfeld S, Zhao D, Pandya SS, Steelman L, Hassan I, Wen PY, Cloughesy TF; INDIGO Trial Investigators. Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma.  N Engl J Med. 2023 Aug 17;389(7):589-601. doi: 10.1056/NEJMoa2304194. Epub 2023 Jun 4.

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