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Conquest - Spring 2013

Collaboration helps speed
drug discovery

MD Anderson is known for its innovative ventures, and the Moon Shots Program, launched last year, is its most visionary. Its focus is on systematically and rapidly converting scientific discoveries into clinical advances that reduce cancer deaths.

Key components of the program are platforms, like the Institute for Applied Cancer Science and Big Data Analytics, which provide specialized expertise and infrastructure. While some platforms are in development, others like IACS are up and running.

Barbara Czako, Ph.D., research scientist in the 
Institute for Applied Cancer Science, works in a 
state-of-the-art chemistry suite to design and 
synthesize novel, safe and effective compounds 
that will serve as the basis for the next generation
of cancer therapies.
Photo: Wyatt McSpadden


By Hilary Graham

Take the extensive knowledge of biology found in academia.

Add the disease expertise of 
MD Anderson’s top clinicians.

Combine with the drug discovery capabilities of the biopharmaceutical industry.

Then, build a bridge that connects them. That’s what MD Anderson has done by establishing the Institute for Applied Cancer Science (IACS).

Driven to bring new therapies to patients, the institute is carrying out drug discovery programs that target tumor types resistant to the standard of care. Their efforts focus on metabolism, epigenetics, immunotherapies and biologics.

Related story: Demystifying big data

Outsmarting cancer cells

While many cancers respond to available treatments, a significant number of patients face treatment-resistant disease, either initially or during recurrence.

Traditionally, researchers have developed drugs to target tumors taken from patients at diagnosis. This approach is why only a portion of patients responds to currently available therapeutics.

Maria Alimova, Ph.D., institute senior research scientist, 
uses high-resolution cell imaging to determine the effect 
of drug candidates in the cell.
Photo: Wyatt McSpadden

“Resistant tumors are not a single disease, instead they are heterogeneous with a multitude of genetic abnormalities and are affected by their surrounding environment,” says Ana Maria Gonzalez-Angulo, M.D., associate professor in 
MD Anderson’s Department of Breast Medical Oncology.

As a patient moves through treatment, resistant tumors circumvent therapy either by mutating to develop resistance via newly acquired biological evasion mechanisms or because a small subset of initially resistant cells emerge as the dominant population.

“To effectively combat hard-to-treat cancers, we need to understand and target fundamental pathways, such as metabolism, which are critical for cancer cell survival,” says Carlo Toniatti, M.D., Ph.D., head of research at IACS. “By designing therapeutics against these indispensable targets, we can ensure that cancer cells will have a difficult time evading therapy.”

Translating innovative research discoveries

When approached, the institute serves as a filter to rigorously evaluate targets identified by MD Anderson investigators. Applying their cumulative industry expertise along the drug discovery and development continuum, IACS researchers provide recommendations on next steps for targets in an unbiased manner, considering scientific merit as well as technical and business feasibility.

Informal meetings in hallways
and stairwells enhance the 
collaboration between Carlo
Toniatti, M.D., Ph.D. (left), 
head of research for the 
Institute for Applied Cancer 
Science, Laura Bover, Ph.D., 
associate professor, and Kui 
Voo, Ph.D., assistant professor, 
both in the Department of 
Genomic Medicine.
Photo: Wyatt McSpadden

Cross-functional teams with diverse expertise in cancer biology, drug discovery and clinical research ensure that all potential strengths and weaknesses in the biology surrounding the target, the drug structure and the appropriate patient population are identified. Once promising programs are thoroughly vetted, IACS can act as an engine to drive programs forward in the drug development process either through internal efforts or in partnership with biopharmaceutical companies.

One such opportunity recently enabled by IACS is the codevelopment and licensing agreement with the pharmaceutical company, GlaxoSmithKline (GSK). The collaboration focuses on the development of therapeutic antibodies that target the OX40 receptor and promote an immune system attack against cancer.

The IACS and the original MD Anderson researchers will work closely with GSK to position the antibodies for clinical success. Reflecting the potential promise of the research, the institution could receive up to $335 million plus royalties from GSK if all milestones are achieved.

“This collaboration also demonstrates IACS’s unique ability to seamlessly integrate drug development expertise with deep biological knowledge and provide patients with promising new therapeutics,” says Giulio Draetta, M.D., Ph.D., professor in MD Anderson’s Department of Genomic Medicine and director of IACS.

Glossary

Altered cellular metabolism is a hallmark of cancer. Understanding the signaling pathways that are hijacked to support cancer cell growth and survival will provide therapeutic strategies to combat malignant cells. Abnormal conditions in the tumor, such as oxygen and nutrient deprivation, require optimized metabolic conditions to support the rapid cellular growth often associated with cancerous tissues.

Epigenetics is the study of changes in gene expression that happen without altering DNA sequence. This field of research is promising because the chemical modifications of DNA and histone proteins that regulate chromatin structure and gene expression are reversible, making ideal targets for therapeutic intervention.

Biologics are a class of therapeutics that are either isolated from natural sources or generated by biological processes in the laboratory. This is in contrast to small molecule drugs, which are generated by chemical synthesis. While there are many categories of biologics, antibodies are particularly well represented in terms of the U.S. Food and Drug Administration-approved products and therapeutic candidates under development.

Immunotherapies engage the body’s immune system to treat, prevent or cure illnesses. One example of immunotherapeutics is antibodies. While cancer cells are foreign to the body and can be detected by the immune system, they often develop ways to avoid destruction. Immunotherapeutics harness the immune system to attack on command, providing patients with a powerful and targeted therapeutic option.

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