New radiation-free targeted therapy detects and eliminates breast cancer tumors in mice

March 31, 2009

Caltech researcher helps develop technique that homes in on aggressive, difficult-to-treat HER2+ breast cancer cells

PASADENA, Calif.--Combining a compound known as a gallium corrole with a protein carrier results in a targeted cancer therapy that is able to detect and eliminate tumors in mice with seemingly fewer side effects than other breast-cancer treatments, says a team of researchers from the California Institute of Technology (Caltech), the Israel Institute of Technology (Technion) and the Cedars-Sinai Medical Center.

A paper describing their work is highlighted in this week's issue of the online edition of the Proceedings of the National Academy of Sciences (PNAS).

Corroles have very similar structures to the porphyrin molecules used in a well-studied cancer treatment known as photodynamic therapy, or PDT, in which porphyrin compounds injected into the body are exposed to specific wavelengths of laser light. The light prompts the porphyrins to produce active, tumor-killing oxygen radicals.

The difference between porphyrins and corroles, says Harry Gray, Caltech's Arnold O. Beckman Professor of Chemistry and founding director of the Beckman Institute, is that some corroles don't require a laser boost to turn lethal. "The striking thing about gallium corroles is that they apparently kill cancer cells in the dark," says Gray. "We don't yet know exactly how this works, but what we've seen so far tells us that it does work."

He notes that "ongoing work in our laboratories focuses on testing our leading hypotheses for elucidating the mechanism of action."

In the experiments described in the PNAS paper, the team paired a gallium corrole with a carrier protein, then aimed it at cells that carry the human epidermal growth factor receptor 2 (HER2). The presence of a HER2 receptor is the hallmark of about 25 percent of breast cancers, and marks those tumors as particularly aggressive and difficult to treat.

In trials in mice, the targeted corrole was able to shrink tumors at doses five times lower than that of the standard chemotherapeutic agent for HER2-positive tumors, a drug called doxorubicin. In contrast with doxorubicin, the corrole was injected into the bloodstream, rather than directly into the tumor.

"We looked at three groups of mice with human tumors," explains paper coauthor Lali Medina-Kauwe, an assistant professor of medicine at the David Geffen School of Medicine at UCLA, and a faculty research scientist in the Department of Biomedical Science at Cedars-Sinai Medical Center in Los Angeles. "In one, we introduced just the protein carrier, without the corrole; tumor growth in those mice did not change. In other mice, we gave the corrole without the carrier protein; this led to some tumor suppression. But it was the last group, the ones that got the corrole with the carrier protein, that experienced the most therapeutic effect."

"The fact that we can target this compound means we can give it at very low concentrations," adds coauthor Daniel Farkas, director of Cedar-Sinai's Minimally Invasive Surgical Technologies Institute. "Using lower concentrations means less toxicity. Doxorubicin tends to have significant heart toxicity; this therapy seems likely to be much less damaging to the heart."

In addition, adds Medina-Kauwe, targeted compounds can seek out tumors wherever they may be. "One of the beauties of targeting," she says, " is that we can go after metastatic tumors that are too small to be seen."

These targeted gallium corroles are not only effective, they're also easy to study, notes Zeev Gross, the Reba May & Robert D. Blum Academic Chair at Technion, the Israeli Institute of Technology, in Haifa, and another of the paper's coauthors. "In most cases, if people want to get a closer look at a drug in vivo, they have to attach a fluorescent probe to it--and that turns it into a different molecule. But in our case, the active molecule we're tracking does the fluorescing. We get to track the original, unmodified molecule and are hence able to follow its distribution among different organs in live animals."

The difficulty in getting to this point, notes Gray, is that corroles have been challenging to synthesize. "Then Zeev came up with a powerful synthetic method to make corroles," he says. "We went from being able to make a couple of milligrams in two years to being able to make two grams in two days. It really puts corroles on the map."

Gray and Gross further add, "It is truly fulfilling to see how the close collaboration between our research groups at Caltech and the Technion, which started 10 years ago with a focus on developing the fundamental science of corroles, led to pharmaceutical utility when we joined forces with Medina-Kauwe and Farkas, who are experts in cellular biology and biomedical imaging technologies."

California Institute of Technology

Minimal Residual Disease and Circulating Tumor Cells in Breast Cancer (Recent Results in Cancer Research)
by Michail Ignatiadis (Editor), Christos Sotiriou (Editor), Klaus Pantel (Editor)

This important book provides up-to-date information on a series of topical issues relating to the approach to minimal residual disease in breast cancer patients. It first explains how the study of minimal residual disease and circulating and disseminated tumor cells (CTCs/DTCs) can assist in the understanding of breast cancer metastasis. A series of chapters then discuss the various technologies available for the detection and characterization of CTCs and DTCs, pinpointing their merits and limitations. Detailed consideration is given to the relevance of CTCs and DTCs, and their detection, to clinical research and practice. The role of other blood-based biomarkers is also addressed, and the closing chapters debate the challenges facing drug and biomarker co-development and the use of CTCs...

Humor After the Tumor: One Woman's Look at Her Year With Breast Cancer
by Patty Gelman (Author), Leslie Zemsky (Illustrator)

Breast cancer survivor Patty Gelman recounts her journey through "Cancer World" in a series of anecdotes, chronicling her year-long struggle with the disease in an upbeat, colloquial, and often candidly funny way. Typical of her unyieldingly positive attitude is the way that Gelman breaks the news to her mother, also a cancer survivor: "Well, it's my turn now!"

Breast Cancer: Early Detection with Mammography: Crushed Stone-like Calcifications: The Most Frequent Malignant Type
by Laszlo Tabar (Author), Tibor Tot (Author), Peter B. Dean (Author)

Praise for this book:This book should be required reading for the multidisciplinary team of physicians and health care professionals who use mammography for breast cancer detection and treatment...a landmark volume in the field of mammography.--RadiologyInternationally renowned breast cancer imagers, Laszlo Tabar and Peter B. Dean, and the eminent breast pathologist, Tibor Tot, distill decades of clinical expertise in this new volume covering the most frequently occurring malignant type of calcifications: the pleomorphic, crushed stone-like calcifications.The book presents a systematic approach to using mammographic features to distinguish different subtypes of breast diseases originating within the terminal ductal lobular unit (TDLU). More than 800 images demonstrate abnormal findings...

Confronting Hereditary Breast and Ovarian Cancer: Identify Your Risk, Understand Your Options, Change Your Destiny (A Johns Hopkins Press Health Book)
by Sue Friedman (Author), Rebecca Sutphen (Author), Kathy Steligo (Author), Mark H. Greene (Foreword)

"Be informed. Be empowered. Be well."If you are concerned that the cancer in your family is hereditary, you face difficult choices. Should you have a blood test that may reveal whether you have a high likelihood of disease? Do you preemptively treat a disease that may never develop? How do you make decisions now that will affect the rest of your life? This helpful, informative guide answers your questions as you confront hereditary breast and ovarian cancer.Developed by Facing Our Risk of Cancer Empowered (FORCE), the nation’s only nonprofit organization dedicated to supporting families affected by hereditary breast and ovarian cancer, this book stands alone among breast and ovarian cancer resources. Equal parts health guide and memoir, it defines complex issues facing previvors and...

The Breast Cancer Survivor's Fitness Plan: A Doctor-Approved Workout Plan For a Strong Body and Lifesaving Results (Harvard Medical School Guides)
by Carolyn Kaelin (Author), Francesca Coltrera (Author), Josie Gardiner (Author), Joy Prouty (Author)

The only breast cancer recovery program designed by a Harvard doctor and survivor and approved by the American Council on Exercise (ACE) Feel healthy again. Regain control of your life. Exciting new research reveals that regular exercise can reduce the chance of breast cancer recurrence and extend your life. Exercise can also help you recover energy, strength, and flexibility diminished by lifesaving breast cancer treatments. Dr. Carolyn Kaelin is a leading breast cancer surgeon who understands the important links among exercise, recovery, and the quality of life--and she is a breast cancer survivor, too. Designed with master trainers Josie Gardner and Joy Prouty, The Breast Cancer Survivor's Fitness Plan features effective, inspiring workouts tailored for each type...

Straight Talk About Breast Cancer: From Diagnosis to Recovery
by Suzanne W. Braddock MD (Author), Jane M. Kercher MD (Author), John J Edney MD (Author), Melanie Morrissey Clark (Author)

This medical handbook serves as an accessible resource for answering the questions of women with breast cancer as well as easing the concerns of their spouses and family members. Drawing on the personal experiences of a breast-cancer survivor and the professional expertise of breast-cancer specialists, this guide outlines the various treatment options for cancer patientsincluding lumpectomy and mastectomy surgeries, radiation treatment, and chemotherapyboth in terms of how they work and the toll they take on a patient’s life. Photographs on breast reconstruction are included as is a complete list of resources and an open discussion of hereditary and reoccurrence risks. The latest information on diagnostics and treatment is provided, making this an essential resource for those...

The Breast Reconstruction Guidebook, Second Edition
by Kathy Steligo (Author)

The best-selling guide to mastectomy and reconstruction has been rewritten and updated. The 2nd edition of The Breast Reconstruction Guidebook retains all the comprehensive information, descriptions ad explanation of the original issue, along with new information about the lattest implant and flap reconstruction procedures, how to find a surgeon who specializes in these newer techniques and much more. No woman wants to lose her breasts. But having a mastectomy doesn't have to mean living without them. How do you find answers about mastectomy and reconstruction when you're still overwhelmed by your diagnosis and treatment? How real will your new breasts look and feel? What if you don't want implants? How painful is the process? Will your insurance cover all the costs? What is recovery...

Fusion of FNA-cytology and gene-expression data using Dempster-Shafer theory of evidence to predict breast cancer tumors.(Hypothesis): An article from: Bioinformation
by Mansoor Raza (Author), Iqbal Gondal (Author), David Green (Author), Ross L. Coppel (Author)

This digital document is an article from Bioinformation, published by Thomson Gale on January 1, 2006. The length of the article is 3652 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser.

Citation Details
Title: Fusion of FNA-cytology and gene-expression data using Dempster-Shafer theory of evidence to predict breast cancer tumors.(Hypothesis)
Author: Mansoor Raza
Publication: Bioinformation (Magazine/Journal)
Date: January 1, 2006
Publisher: Thomson Gale
Page: 170(6)

Distributed by Thomson...

Breast Cancer: 50 Essential Things to Do
by Greg Anderson (Author), Erica A. Harvey (Introduction), Christine Northrup MD (Introduction)

2.5 million women in the U.S. have had a breast cancer diagnosis; more than 200,000 women are diagnosed each year. While recovery and survival rates have improved, selecting a treatment plan can be confusing and overwhelming.Breast Cancer: 50 Essential Things You Can Do offers a roadmap for women facing breast cancer. Cancer-survivor Greg Anderson, a recognized pioneer in the field of integrated cancer care, has guided tens-of-thousands of cancer patients to health and healing over the past 25 years, through his books and his Cancer Recovery Foundation. In this new book he offers critical information about the major issues patients face following a breast cancer diagnosis, and shows how to implement a comprehensive recovery plan that maximizes opportunity for healing and recovery.This is...

100 Questions & Answers About Advanced & Metastatic Breast Cancer
by Lillie D. Shockney (Author), Gary R. Shapiro (Author)

EMPOWER YOURSELF! Whether You're A Newly Diagnosed Patient, Survivor, Or Loved One Of Someone Suffering From Advanced Breast Cancer, 100 Questions & Answers About Advanced And Metastatic Breast Cancer, Second Edition Offers Essential And Practical Guidance. Providing Both Doctor And Patient Perspectives, This Updated And Revised Edition Offers Authoritative Answers To The Most Commonly Asked Questions About Advanced And Metastatic Breast Cancer Including Diagnosis, Treatment, Post-Treatment Quality Of Life, Alternative Medicine, Targeted Therapy, And Coping Strategies. Written By Experts From Johns Hopkins University And Medical Center, This New Edition Is An Invaluable Resource For Anyone Coping With The Physical And Emotional Turmoil Of This Disease.