MD Anderson institute joins other academic moves to streamline drug development
In recent years, the “Valley of Death” in drug development has grown deadlier as pharmaceutical giants have trimmed back on preclinical and early clinical research. Individual research teams and institutions are striving to fill this gap, and a few cancer research groups have launched major initiatives (see “Drug Discovery Gets an Academic Push,” Cancer Discovery 2011;1:93–4).
The newest and one of the largest is MD Anderson Cancer Center's Institute for Applied Cancer Science (IACS) in Houston, formally launched in November 2011.
Building on “Industrialized” Models
The MD Anderson initiative adopts an approach taken by groups including the Belfer Institute for Applied Cancer Science at Boston's Dana-Farber Cancer Institute (DFCI) and the UK Institute of Cancer Research's Cancer Therapeutics Unit.
Created in 2006, Belfer represents a fusion between the Belfer Center for Cancer Genomics (founded in 1999 by Lynda Chin, MD, now scientific director of the IACS) and the Center for Applied Cancer Science (founded in 2004 by Ronald DePinho, MD, now president and CEO of MD Anderson).
Belfer is just one of DFCI's 12 integrative research centers, about half of which fall under the umbrella of drug discovery, evaluation, and development, says Barrett Rollins, MD, PhD, DFCI's chief scientific officer. “It's a delicate dance, trying to be accountable for applied progress while honoring the notion of unfettered investigation,” says Rollins.
DFCI invested $6.1 million in Belfer between 2005 and 2009; other support comes from philanthropy, foundations, corporate partnerships, and grants. The institute has garnered major contracts with Merck and Sanofi, both now developing therapies in collaboration with Belfer scientists.
The Cancer Therapeutics Unit in Sutton, Surrey (UK), led by Paul Workman, PhD, pursues similar goals. This group has 160 staff and annual funding of around £15 million (about $23 million), 50% from the charity Cancer Research UK.
“Our first step was to build teams of interdisciplinary experts, including biologists, medicinal chemists, structural biologists, molecular modelers, and specialists in chemoinformatics, pharmacokinetics, tumor models, biomarkers, and early clinical trials,” says Workman.
![Russell McSweeney, principal research associate at the Belfer Institute for Applied Cancer Science, uses high-throughput cell-line screening to accelerate target identification and validation. [Photo courtesy of Dana-Farber Cancer Institute/Sam Ogden.]](/view-large/figure/8402786/101photo1.jpeg)
Russell McSweeney, principal research associate at the Belfer Institute for Applied Cancer Science, uses high-throughput cell-line screening to accelerate target identification and validation. [Photo courtesy of Dana-Farber Cancer Institute/Sam Ogden.]
Russell McSweeney, principal research associate at the Belfer Institute for Applied Cancer Science, uses high-throughput cell-line screening to accelerate target identification and validation. [Photo courtesy of Dana-Farber Cancer Institute/Sam Ogden.]
Pushing the Pipeline
At MD Anderson's new institute, “our goal is to develop compounds and move them as far as possible along the drug-discovery continuum,” says Chin, the new organization's scientific director. “Every gate we pass through on that road lowers the risk to a potential pharmaceutical company partner.”
MD Anderson's clinical infrastructure, ability to conduct investigational new drug studies, and generous financial support will help. The institution has committed up to $15 million annually for 5 years, and IACS leaders hope to raise at least $42 million more by 2016.
The IACS offers competitive salaries to recruit not just scientists but top industry experts, some of whom may be drawn by the greater security of an academic appointment, says Chin. Among the hires, Philip Jones, PhD, who led several oncology drug discovery programs at Merck, serves as head of drug discovery for the IACS.
Embedding the equivalent of a start-up biotech company within an academic environment can speed progress, Chin notes: “For example, we don't have to spend time negotiating and drawing up a contract to license a genetically engineered mouse model, because we already have it.”
The IACS hopes to have novel drug candidates for biomarker-driven trials within 5 years. “It's too early to say where our focus will be,” says director Giulio Draetta, MD, PhD. “But I'm personally interested in working on brain, pancreatic, and ovarian cancers, where the need for new treatments is huge.”
Although MD Anderson's Institute for Applied Cancer Science is just starting, the UK Institute of Cancer Research's Cancer Therapeutics Unit has discovered 14 drug candidates over the last 5 years, with 6 drugs progressing into the clinic and many licensed to industry, including abiraterone (Zytiga; Johnson & Johnson), approved last year for late-stage prostate cancer.
One early but promising finding from the Belfer Insti-tute for Applied Cancer Science is the identification by Ronald DePinho, MD, and Lynda Chin, MD (both now at MD Anderson), and colleagues of a 4-gene signature that may help distinguish slow-growing prostate tumors from more aggressive, lethal tumors (Nature 2011;470:269–73). Metamark Genetics, Inc., founded in Cambridge, MA, by Chin, is developing a prognostic genetic test based on the findings.
In another recent advance, Belfer's James Bradner, MD, and colleagues discovered a molecule that indirectly targets activation of c-Myc, an oncoprotein previously considered “undruggable” (Cell 2011;146:904–17). The molecule, JQ1, is licensed to Tensha Therapeutics, also of Cambridge, MA.
For more news on cancer research, visit Cancer Discovery online at www.AACR.org/CDnews.
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