January 14, 2003
Study aims to solve puzzle of ER-negative breast tumors
Hunting for overactive genes
Kornelia Polyak, MD, PhD, a Dana-Farber physician-scientist, has used a cutting-edge technique to detect genes that may be extremely active — "highly expressed" — in cancer cells, as well as genes that are highly expressed in normal cells. Dr. Polyak has identified a gene called S100A7/psoriasin that is extremely active in an early stage of breast cancer, ductal carcinoma in situ, or DCIS, and is not expressed in any normal adult tissue. She is pursuing the possibility that the substance could be detected in a patient's blood or other body fluid as an early warning "biomarker" of ER-negative cancer.
Kornelia Polyak, MD, PhD, hunts for abnormal genes in breast cancer.
These are only a few of the avenues being followed in the collaboration. Others include "genomic fingerprinting" — another method of looking for genes or groups of genes that are unusually active in diseased cells; probing possible culprits among signaling molecules inside cancer cells that regulate cell growth; and examining the role of the nuclear factor kappa B (NF-kB) signaling pathway in the growth and survival of ER-negative breast cancers.
While this research is predominantly basic laboratory science, it could lead eventually to drug candidates being tested in patients.
"We really want to move away from harsh, toxic chemotherapy treatments and toward more targeted therapies," says Carol Matyka, a breast cancer survivor who also is a consumer advocate on the project. "One of our [the advocates'] roles is to bring the face of cancer to the table, to make it real and relevant. We are here to ask, 'What does this mean?' and 'Where is this going to go?'"
The knotty ER-negative problem will not yield its secrets easily. Dr. Brown foresees a lengthy battle — and a costly one. Among other goals, Dr. Brown says he would like to have the ability to decipher the DNA sequence of all the genes involved in ER-negative cancer.
"To find all the mutations in all the genes," he says, "would be extremely valuable."
(This story first appeared in the Winter/Spring 2003 edition of Turning Point.)
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