Oral drug showing promise for breast cancer prevention in a mouse model

December 16, 2003

The oral drug ZD1839, also known as gefitinib, prevented the development of estrogen receptor (ER)-negative breast cancer in a mouse model, which raises the possibility that the drug could be a preventive agent for ER-negative breast cancer. The results appear in the December 17 issue of the Journal of the National Cancer Institute.

ER-negative breast cancers are not dependent on estrogen to grow and do not respond to antiestrogen drugs such as tamoxifen and raloxifene. ZD1839, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, blocks the cellular signaling pathway that contributes to tumor survival and growth, and studies have shown that ZD1839 is effective at inhibiting the growth of various types of cancer cells, including breast cancer cells.

To test whether ZD1839 can inhibit the growth of ER-negative breast cancer cells, Chunhua Lu, M.D., Ph.D., and Powel H. Brown, M.D., Ph.D., of the Baylor College of Medicine in Houston, and their colleagues treated ER-negative normal, immortalized (i.e., precancerous), and cancerous breast cells with ZD1839. They also examined the effect of ZD1839 on the development of ER-negative breast tumors in transgenic mice.

Treatment with ZD1839 suppressed the growth of ER-negative normal, immortalized, and cancerous breast cells. Moreover, ZD1839 treatment of transgenic mice that normally develop breast tumors in approximately 230 days delayed the formation of ER-negative tumors to more than 310 days. ZD1839 also reduced proliferation of normal breast cells by 20.3% and of tumor cells by 42%.

In an accompanying editorial, Dennis J. Slamon, M.D., Ph.D., of the University of California at Los Angeles Jonsson Comprehensive Cancer Center, and his colleagues commend the new findings, but caution that long-term safety data are not available for ZD1839. They point out that some patients taking ZD1839 for non-small-cell lung cancer have developed interstitial lung disease, a rare but potentially dangerous side effect, particularly if ZD1839 is used as a chemopreventive agent in healthy women.

In addition, they say, the effectiveness of ZD1839 and other EGFR inhibitors may be limited to a subpopulation of patients in whom EGFR is involved in tumor formation or growth. "Before we develop gefitinib as a chemopreventive agent, further research is needed to find and validate predictive factors that can be used to identify patients and healthy women likely to respond to gefitinib as a therapeutic and chemopreventive agent," they conclude.
Contact: Kimberlee Barbour, Baylor College of Medicine, 713-798-7971; fax: 713-798-3692, kbarbour@bcm.tmc.edu.

Editorial: Kim Irwin, Jonsson Comprehensive Cancer Center, 310-206-2805, kirwin@mednet.ucla.edu. Lu C, Speers C, Zhang Y, Xu X, Hill J, Steinbis E, et al. Effect of epidermal growth factor receptor inhibitor on development of estrogen receptor-negative mammary tumors. J Natl Cancer Inst 2003;95:1825-33.

Editorial: Konecny GE, Wilcon CA, Slamon DJ. Is there a role for epidermal growth factor receptor inhibitors in breast cancer prevention. J Natl Cancer Inst 2003;95:1813-15.

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oupjournals.org/.

Journal of the National Cancer Institute

Related Cancer Cells Articles from Brightsurf:

Cancer researchers train white blood cells to attacks tumor cells
Scientists at the National Center for Tumor Diseases Dresden (NCT/UCC) and Dresden University Medicine, together with an international team of researchers, were able to demonstrate that certain white blood cells, so-called neutrophil granulocytes, can potentially - after completing a special training program -- be utilized for the treatment of tumors.

New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed
Scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill some multiplying human breast cancer cells by selectively attacking the core of their cell division machinery.

Breast cancer cells use message-carrying vesicles to send oncogenic stimuli to normal cells
According to a Wistar study, breast cancer cells starved for oxygen send out messages that induce oncogenic changes in surrounding normal epithelial cells.

Breast cancer cells turn killer immune cells into allies
Researchers at Johns Hopkins University School of Medicine have discovered that breast cancer cells can alter the function of immune cells known as Natural killer (NK) cells so that instead of killing the cancer cells, they facilitate their spread to other parts of the body.

Breast cancer cells can reprogram immune cells to assist in metastasis
Johns Hopkins Kimmel Cancer Center investigators report they have uncovered a new mechanism by which invasive breast cancer cells evade the immune system to metastasize, or spread, to other areas of the body.

Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.

Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.

First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.

Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.

Read More: Cancer Cells News and Cancer Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.