Clarke Labs

Research in Robert Clarke's Laboratory

Monastic ruins at Nendrum (Co. Down, Northern Ireland) showing the remains of the church and round tower. The abbey was reputedly founded by Saint Mochaoi in the 5th century AD.

These are the breast cancer research pages of Dr. Robert Clarke's laboratory at Georgetown University. On this page you will find links to our ongoing breast cancer research projects. More information on Dr. Clarke may be found at the Faculty web page, and at the Community of Science. Our laboratory web pages also include a FTP data exchange/Login page and a listing of some of our prior laboratory members. Navigation links to other pages withing our site are provided in the box to the left.

Dr. Robert Clarke, Ph.D., D.Sc., F.I. Biol., F.R.S. Chem., F.R.S. Med.

Professor of Oncology and Physiology & Biophysics

W405A Research Building

Georgetown University School of Medicine

3970 Reservoir Rd NW

Washington, DC 20057, U.S.A.

Telephone: (202) 687-3755

Telefax: (202) 687-7505

Email: clarker@georgetown.edu

Dr. Clarke also is the Interim Director of the Biomedical Graduate Research Organization at Georgetown University, Associate Vice President of Georgetown University Medical Center, the Co-Chair of the Division of Molecular Endocrinology, Nutrition and Obesity in the Department of Oncology, and Co- Director of the Breast Cancer Program at the Lombardi Comprehensive Cancer Center

Dr. Clarke is Vice President for Academic Outreach for BioLink
USA-Ireland, an organization that connects life scientists from Ireland
currently living in the US with each other and with the life sciences
community in Ireland, both industry and academia. For more information
on this organization visit http://www.biolinkusaireland.com

Breast Cancer

In the next 12 months, the American Cancer Society estimates that there will be over 62,000 newly diagnosed cases of in situ breast cancer and approximately 214,000 newly diagnosed cases of

in situ breast cancer is of two forms: ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS)
DCIS and LCIS do not show evidence of having spread into adjacent normal breast tissue
Invasive breast cancer shows evidence of having spread (invaded) into adjacent normal breast tissue

invasive breast cancer in the United States. Over 41,000 women will die of breast cancer during this period, the equivalent of one breast cancer death every 13 minutes. Lifetime risk of developing breast cancer is modified by several factors related to development (e.g., weight at birth, age at menarche), reproductive life (e.g., parity, breast feeding, age at menopause), lifestyle (e.g., obesity, alcohol consumption),

Most breast cancers arise in women who have no family history of breast cancer (often called sporadic or spontaneous breast cancer). 5-10% of breast cancer cases arise in women who have a strong family history of breast cancer, these breast cancers result from gene mutations.
The most common mutations are those in the BRCA1 and BRCA2 genes, which account for about one-half of all inherited (sometimes referred to as familial or hereditary) breast cancers.
In families with a pattern of inherited breast cancer (high incidence of breast cancer but not other cancers), about one-third of the cases are due to mutations in BRCA1 or BRCA2.
Women with an inherited BRCA1 or BRCA2 mutation have up to an 80% risk of developing breast cancer during their lifetime.

inheritance (e.g., mutant BRCA1) . The molecular events that drive breast cancer progression are largely unknown in both sporadic and inherited breast cancers. Randomized clinical trials and large meta-analyses show that breast cancer patients derive a statistically significant survival benefit from chemotherapy and endocrine therapy,

Antiestrogens affect function of the estrogen receptor usually by preventing it from binding estrogens
Some investigators choose to group antiestrogens into functional subgroups such as SERMs (selective estrogen receptor modulators, e.g., Tamoxifen) and SERDs (selective estrogen receptor degradors, e.g., Fulvestrant)
SERMs generally function as partial agonsists (exhibit propoerteis of both estrogen and an estrogen antagonist) and can act differently in different tissues, e.g., Tamoxifen can be an antagonist (estrogen antagonist) in breast cancer and an agonist (estrogen) in bone. Tamoxifen is the best known SERM, others include Raloxifen (also known as Evista) and Tormifene (also known as Fareston)

Tamoxifen (antiestrogen), doxorubicin (anthracycline) and paclitaxel (taxane) being among the most effective single agents. The survival benefit gained from current systemic therapies largely reflects the abilities of cytotoxic and endocrine agents to modify breast cancer cell survival such that cells are driven down an irreversible cell death pathway. Despite the benefits of therapy, advanced breast cancer largely remains an incurable disease for most women, and new treatment regimens and schedules have led to only incremental decreases in breast cancer related mortality. A better understanding of the factors that regulate breast cancer cell survival/death is central to improving breast cancer outcomes in women.

Breast Cancer Research in Dr. Robert Clarke’s Laboratory

Our primary research interests are focused on obtaining a better understanding of how breast cancer cells acquire resistance to systemic endocrine and cytotoxic therapies and the effects of hormones and growth factors on breast cancer cell proliferation, survival and apoptosis. We study cellular, molecular, and pharmacological resistance mechanisms in an integrated, multidisciplinary, and translational approach. Our studies have a strong endocrinologic basis, e.g., our interests include the interactions among endocrine and cytotoxic therapies; our major emphasis is on antiestrogen resistance and hormone independence. We also are interested in the molecular and endocrinologic factors that affect the ability of obesity to modify breast cancer outcomers.

We apply a wide range of state-of-the-art cellular, molecular, and bioengineering/bioinformatics approaches to both experimental models (several of which we derived specifically for these studies) and to specimens from breast cancer patients.

The links in the menu to the left will take you to pages that provide more information on our studies, contain brief descriptions of the work, and list selected publications in each field. Since these studies are tightly integrated, a few of our publications may be listed in more than one section. Our gene expression microarray pages contain further links to our own studies and additional/supplementary data, links to other published studies, and links to various useful gene expression microarray pages.

Dr. Clarke's Publications Short Biography