Friday, December 9, 2011

Novel Approach to Treating Breast Cancer Shows Great Promise in Loyola Pilot Study

Experimental Drug Targets Cancer Stem Cells

MAYWOOD, Ill. -- In a novel therapeutic approach to treating breast cancer, Loyola University Medical Center researchers are reporting positive results from a clinical trial of a drug that targets tumor stem cells.

Existing cancer drugs are effective in killing mature cancer cells. But a handful of cancer stem cells are resistant to such drugs. They survive and go on to develop into new tumor cells.

A pilot study at Loyola found that an experimental drug known as a "notch inhibitor" appears to block this process by turning off key genes. Kathy Albain, MD, who led the study, presented findings Dec. 7 during the 2011 CTRC-AACR San Antonio Breast Cancer Symposium.

Albain collaborated with scientists from Loyola, University of Mississippi Cancer Center, Baylor Breast Center and Merck Oncology.

"Our results suggest a potential role that notch inhibitors could play in optimizing existing therapies and in overcoming resistance to cancer drugs," Albain said.

The so-called notch protein promotes tumor growth and survival. The protein is present on the surface of cancer stem cells. The protein latches on to other cells, and the resulting "molecular handshake" activates various genes in the stem cells. Activating these genes, in effect, makes the stem cells resistant to common cancer drugs.

The study included 20 patients who finished all therapy. The women all had early-stage, estrogen-receptor-positive breast cancer.

Prior to surgery, the patients received one of two commonly used drugs, tamoxifen or letrozole. These drugs work by blocking estrogen stimulation of breast cancer cells. In addition to tamoxifen or letrozole, patients also received the experimental notch-inhibitor drug, MK-0752.

Following treatment with the notch inhibitor, patients underwent biopsies to provide tumor specimens. Researchers found that the drug turned off the key genes that in effect would have kept the tumor stem cells resistant to conventional drugs.

"The notch inhibitor appears to be doing what it is intended to do," said Clodia Osipo, PhD, a breast cancer scientist in Loyola's Cardinal Bernardin Cancer Center.

There were minimal side effects from either the notch inhibitor or the estrogen-blocking drugs. One patient experienced puffy eyes and coughing and four patients experienced facial acne. No patients experienced diarrhea or surgical complications.

The purpose of the study was to determine how well the notch inhibitor is tolerated and how it affects the expression of critical genes in cancer stem cells. The next step is to determine how effective the drug would be in treating breast cancer.

Researchers proposed a randomized clinical trial, in which patients who received estrogen-blocking drugs before surgery would be compared to patients who received estrogen-blocking drugs plus a notch inhibitor.

Clinical trial costs were funded by Swim Across America, an annual event in which swimmers raise money for the Cardinal Bernardin Cancer Center. Merck Oncology supplied the drugs and provided additional support.

Albain is a professor in the Department of Medicine, Division of Hematology/Oncology at Loyola University Chicago Stritch School of Medicine.

Co-authors of the study are Cheryl Czerlanis, Andrei Zlobin, Kyle R. Covington, Prabha Rajan, Constantine Godellas, Davide Bova, Shelly S. Lo, Patricia Robinson, Sharfi Sarker, Ellen R. Gaynor, Richard Cooper, Gerard Aranha, Kathy Czaplicki, Barbara Busby, Paola Rizzo, Tim Demuth, Patrick Stiff, Suzanne Fuqua and Lucio Miele.

About Loyola University Health System

Loyola University Health System (LUHS) is part of Trinity Health. Based in the western suburbs of Chicago, LUHS is a quaternary care system with a 61-acre main medical center campus, the 36-acre Gottlieb Memorial Hospital campus and more than 30 primary and specialty care facilities in Cook, Will and DuPage counties. Loyola University Medical Center’s campus is conveniently located in Maywood, 13 miles west of Chicago’s Loop and 8 miles east of Oak Brook, Ill. At the heart of the medical center campus is a 559-licensed-bed hospital that houses a Level 1 Trauma Center, a Burn Center and the Ronald McDonald® Children's Hospital of Loyola University Medical Center. Also on campus are the Cardinal Bernardin Cancer Center, Loyola Outpatient Center, Center for Heart & Vascular Medicine and Loyola Oral Health Center as well as Loyola University Chicago Stritch School of Medicine, Loyola University Chicago Marcella Niehoff School of Nursing and the Loyola Center for Fitness. Loyola's Gottlieb campus in Melrose Park includes the 255-licensed-bed community hospital, the Professional Office Building housing 150 private practice clinics, the Adult Day Care, the Gottlieb Center for Fitness, Loyola Center for Metabolic Surgery and Bariatric Care and the Loyola Cancer Care & Research at the Marjorie G. Weinberg Cancer Center at Melrose Park.

Trinity Health is a national Catholic health system with an enduring legacy and a steadfast mission to be a transforming and healing presence within the communities we serve. Trinity is committed to being a people-centered health care system that enables better health, better care and lower costs. Trinity Health has 88 hospitals and hundreds of continuing care facilities, home care agencies and outpatient centers in 21 states and 119,000 employees.