Nav: Home

Drug targeting tumor metabolism discovered by MD Anderson's Institute for Applied Cancer Science enters clinical trial

October 26, 2016

The University of Texas MD Anderson Cancer Center's Institute for Applied Cancer Science (IACS) has initiated the first clinical study of a novel drug designed to starve cancer cells, IACS-10759. The study will enroll patients with acute myeloid leukemia (AML) and is supported by a $3.5 million investment from The Leukemia & Lymphoma Society (LLS) Therapy Acceleration Program®. Recent approval from the U.S. Food and Drug Administration to begin clinical studies was based on compelling activity upon IACS-10759 treatment in multiple preclinical models of AML.

"We're delighted that this milestone clinical trial, bringing forth an entirely new approach for this difficult disease, has earned the support of The Leukemia & Lymphoma Society," said Giulio Draetta, M.D., Ph.D., head of Therapeutics Development at MD Anderson. "We are hopeful that we will soon see in patients the promising response to IACS-10759 that we observed in preclinical models."

Starving malignancies

All cells rely on two processes to generate the energy they need to survive: oxidative phosphorylation (OXPHOS) and glycolysis. IACS-10759 interferes with one of the molecular machines within mitochondria to inhibit OXPHOS. Normal cells can get around OXPHOS inhibition by turning up glycolysis; however, the IACS team led by Emilia di Francesco, Ph.D., associate director of Medicinal Chemistry, and Joe Marszalek, Ph.D., head of Translational Biology, identified a highly potent and specific OXPHOS inhibitor to target cancer cells that are unable to compensate in that way, and survive.

"The IACS model emphasizes the need for us to deeply understand the biological effects of drugs," Draetta said. "We want to increase the precision with which we identify and develop new molecules, to ask critical questions about the effects of any new drug within the most relevant contexts."

To accomplish this, Marszalek and Di Francesco, forged collaboration with Marina Konopleva, M.D., Ph.D., professor of Leukemia, who could offer clinical expertise and powerful models for studying AML.

The team has since identified subgroups in other hematological malignancies and a variety of solid cancers that could also be vulnerable to OXPHOS inhibition. "We're already working closely with several MD Anderson Cancer Moon Shots Program teams to develop IACS-10759 treatment for patients whose tumors rely on oxidative phosphorylation," said IACS Executive Director Philip Jones, Ph.D.

AML patients need new options

According to Konopleva, who leads the clinical trial, about 40 percent of younger patients with AML survive long term, while survival for patients over age 65 drops to about 10 percent. AML has been treated mainly with chemotherapy combinations for decades, and patient outcomes have not improved for the last 40 years.

LLS recently announced its Beat AML Master Trial, a collaborative multi-site, multi-arm clinical trial to develop a precision medicine approach to treating patients with AML. LLS estimates there will be 19,950 new cases of AML diagnosed in 2016, most in adults, and about 10,430 deaths.

"LLS is going on the offensive against AML, a disease that has seen little change in the standard of care in more than 40 years," said Lee Greenberger, Ph.D., LLS's chief scientific officer. "Through our Beat AML initiative and other promising projects, such as this very innovative approach being developed by the MD Anderson team, we are hoping to change the paradigm of treatment for this deadly disease."
This first trial of IACS-10759 will enroll up to 48 patients with relapsed or resistant AML. The primary objectives aim to determine the safety and tolerability of IACS-10759 and to establish a maximum tolerated dose as well as a recommended dose for a phase 2 trial. Secondary objectives will evaluate pharmacokinetics and pharmacodynamics, as well as progression-free and overall survival.

MD Anderson has intellectual property surrounding IACS-10759 that could provide a financial benefit to the institution through activities such as licensing or the technology being sold to a private company for further development. All research at MD Anderson including clinical development will be managed under the institution's policies and procedures to address any such conflicts.

IACS and the Moon Shots Program

Launched in 2011 and developed as part of MD Anderson's Cancer Moon Shots Program, IACS is a drug discovery biopharmaceutical unit embedded within the world's No. 1 cancer hospital. With a Bench-at-Bedside approach, the seamless integration of drug discovery and clinical translation, IACS aims to contribute to MD Anderson's mission of Making Cancer History. In addition to IACS-10759, IACS has a robust drug discovery pipeline of molecules targeting cancer cell metabolism, epigenetics, and other novel targets.

MD Anderson's Moon Shots Program is an ambitious effort to reduce cancer deaths by more rapidly developing and implementing advances in prevention, early detection and treatment based on scientific discoveries. Announced in 2012, the program now comprises 13 moon shots focused on a variety of the most challenging cancers backed by 10 platforms that provide deep expertise, cutting-edge technology and infrastructure to support innovative approaches.

University of Texas M. D. Anderson Cancer Center

Related Leukemia Articles:

New leukemia treatment outperforms standard chemotherapies
Researchers at The Australian National University (ANU) are working on a new treatment for an aggressive type of leukemia that outperforms standard chemotherapies.
Team uncovers novel epigenetic changes in leukemia
UT Health San Antonio researchers discovered epigenetic changes that contribute to one-fifth of cases of acute myeloid leukemia (AML), an aggressive cancer that arises out of the blood-forming cells in bone marrow.
Gene mutations cause leukemia, but which ones?
Watanabe-Smith's research, published today in the journal Oncotarget, sought to better understand one 'typo' in a standard leukemia assay, or test.
Halting lethal childhood leukemia
Scientists have discovered the genetic driver of a lethal childhood leukemia that affects newborns and infants and identified a targeted molecular therapy that halts the proliferation of leukemic cells.
Obesity-associated protein could be linked to leukemia development
Cancer researchers at the University of Cincinnati College of Medicine have found an obesity-associated protein's role in leukemia development and drug response which could lead to more effective therapies for the illness.
Tracking down therapy-resistant leukemia cells
Dr. Irmela Jeremias from Helmholtz Zentrum M√ľnchen and her colleagues have succeeded in finding a small population of inactive leukemia cells that is responsible for relapse of the disease.
Personalizing chemotherapy to treat pediatric leukemia
A team of UCLA bioengineers has demonstrated that its technology may go a long way toward overcoming the challenges of treatment for acute lymphoblastic leukemia, among the most common types of cancer in children, and has the potential to help doctors personalize drug doses.
Putting a brake on leukemia cells
Cancer cells need a lot of energy in order to divide without limits.
Study provides new clues to leukemia resurgence after chemotherapy
For the first time, researchers have discovered that some leukemia cells harvest energy resources from normal cells during chemotherapy, helping the cancer cells not only to survive, but actually thrive, after treatment.
Improving models of chronic lymphocytic leukemia
In this issue of JCI Insight, Nicholas Chiorazzi and colleagues at the Feinstein Institute for Medical Research sought to understand a model of chronic lymphocytic leukemia in which patient cancer cells are transplanted into immunocompromised mice.

Related Leukemia Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...