Foundation Awards High-level Grants to Support Clinical Research

The ASCO Cancer Foundation^® continues its tradition of supporting the best and most innovative cancer research by awarding two Advanced Clinical Research Awards (ACRAs) and a Translational Research Professorship grant in 2009, presented at the most recent ASCO Annual Meeting.

Shanu Modi, MD, and Ingo Mellinghoff, MD, both of Memorial Sloan-Kettering Cancer Center (MSKCC), are the recipients of this year’s ACRAs, three-year awards of $450,000 presented by the Foundation for clinical or translational research with a patient-oriented focus. Dr. Modi received the ACRA for her work in the field of breast cancer (supported by The Breast Cancer Research Foundation^®), and Dr. Mellinghoff received the first ACRA dedicated to support glioma research (supported by Genentech BioOncology™).

Merrill J. Egorin, MD, FACP, received the 2009 Translational Research Professorship for his significant contributions to the direction of translational cancer research and his dedication to mentoring. The Translational Research Professorship, a five-year grant totaling $500,000, is intended to support qualified individuals who are dedicated to bringing advances in basic sciences into the clinical arena and to mentoring other translational researchers. The 2009 Translational Research Professorship is supported by Genentech BioOncology™.

ACRA Winners’ Research Pursues Molecular Therapies

	Ingo Mellinghoff, MD, (left) and Shanu Modi, MD

The most cutting-edge oncology research zeroes in on the aspects of cancer that have eluded current available treatments. The two winners of ASCO’s 2009 ACRAs are pursuing science of this nature, which they hope will advance the treatment of patients with breast cancer and glioma.

Dr. Modi’s research, “PU-H71: A Novel HSP90 Inhibitor for the Treatment of Breast Cancer,” is the latest development in a body of research conducted at MSKCC on the action of HSP90, a protein involved in the progression of breast cancer and its resistance to treatment. Although previous research has suggested the viability of HSP90 inhibitors against HER2-positive breast cancer, patients with triple-negative breast cancer did not seem to benefit from these treatments. Dr. Modi’s investigation of PU-H71 shows that this particular type of HSP90 inhibitor could be beneficial for women with this aggressive subtype of the disease.

“Unlike other breast cancer types for which we have targeted therapies, there are no specific targets identified for triplenegative breast cancers. Therefore we rely on chemotherapy, which works very well, but only for a proportion of patients. It’s clear that we urgently need novel agents and approaches,” Dr. Modi said. “I think there’s such strong preclinical data to support the development of PU-H71 that it has to be taken to the next step.”

Dr. Modi’s group will begin phase 0 clinical trials for PU-H71 in 2009, and she hopes that the study will progress to phase I trials before the end of the year.

Dr. Mellinghoff is the recipient of ASCO’s first ACRA for glioma research. His study, “Identification of Critical Signal Transduction Nodes during Glioma Progression,” investigates the possibility that gliomas may be more responsive to therapy with signal transduction inhibitors if they are treated earlier in the disease process.

“Low-grade gliomas often afflict young patients, and these patients are treated with a combination of surgery, radiation, and/or chemotherapy,” Dr. Mellinghoff said. “We hope that our studies will point toward new molecular targets to prevent or at least delay the progression of these tumors to high-grade gliomas.”

During his training, Dr. Mellinghoff saw great potential in the cutting-edge science used in the study and treatment of cancer.

“My interests in medical school always gravitated toward the molecular basis of human disease. I was impressed by how quickly the combination of rigorous basic science and its logical clinical application transformed the treatment of HIV [human immunodeficiency virus],” he said. “Based on emerging insights into oncogenes and tumor suppressor genes, cancer seemed like a field with great opportunities for similarly transformative science.”

As a previous recipient of a Young Investigator Award (YIA) from the Foundation, he feels that ASCO has influenced his career in a number of ways.

“In addition to the very generous funding, the ACRA will provide me an opportunity to exchange ideas and forge collaborative efforts with colleagues working on related aspects of glioma biology,” he said.

Pharmacology Expert Awarded Translational Research Professorship

	"My job is to run a greenhouse—to maintain an environment in which really smart young people people can put down roots, grow, and flower." —Merril J. Egorin, MD

Dr. Egorin, a mentor to five junior faculty members, emphasized the mentorship component of the Translational Research Professorship.

“The people who were my mentors were incredibly giving, and it’s nice to be able to carry on that tradition and try to inculcate the next generation of investigators,” he said. He added that the grant will aid the development of his younger colleagues just beginning a career in translational research: “My job is to run a greenhouse—to maintain an environment in which really smart young people can put down roots, grow, and flower.”

Dr. Egorin is a Professor of Medicine and Pharmacology at the University of Pittsburgh School of Medicine. He also serves as Co-Director of the Molecular Therapeutics/Drug Discovery Program, and as Director of the Clinical Pharmacology Analytical Facility Core at the University of Pittsburgh Cancer Institute (UPCI).

Dr. Egorin and his colleagues study different approaches to using poly (ADPribose) polymerase (PARP) inhibitors. The grant will provide crucial funding to increase the coordination and expansion of the University of Pittsburgh’s program on the studies of the PARP inhibitor ABT-888 as a single agent in BRCA-mutated or dysfunctional malignancies, or in combination with cytotoxic chemotherapeutic agents against a broader range of cancers.

“In the first case, these tumors—with this one genetic defect—are exquisitely sensitive to what this class of drugs does, [so] you may not need to use anything else,” Dr. Egorin explained. “In the other case, you’re using [the inhibitor] to augment or enhance the activity of things that are already known to have some activity by modulating a potentially important resistance mechanism.”

Dr. Egorin noted that the use of singleagent PARP inhibitors does not lead to myelosuppression, nausea, vomiting, hair loss, or immunosuppression. “[PARP inhibitors] are a very interesting class of compounds that can be used as adjuncts to other forms of chemotherapy,” he said. “Possibly the most exciting thing of all would be to use them in this concept of synthetic lethality, and to go after an Achilles heel of tumor cells.”

The UPCI phase I studies of ABT-888 will be translated into phase II studies in a variety of malignancies including breast, ovarian, pancreatic, and prostate cancers.

For more information on the grants and awards offered by the Foundation, visit www.ascocancerfoundation.org.