Transcript Dr. Jesse Ellman – Cell Biology in Breast Cancer

CELLULAR BIOLOGY IN
BREAST CANCER
JESSE ELLMAN MD
SEPT 2010
CLINICAL ASSISTANT PROFESSOR
DEPT OB GYN AND WOMENS HEALTH
WE MAY BE ENTERING A NEW PHASE IN
MEDICINE IN DIAGNOSIS AND
TREATMENT OF MANY TUMORS
CELLULAR BIOLOGY IN
BREAST CANCER
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PLAYS A PART IN TWO MAJOR AREAS
1.TARGETED THERAPY
2.PROGNOSTICATION OF RECURRENCES
IS THE STUDY OF GENES,ENZYMES AND
CELLULAR FUNCTION-MICROBIOLOGY-AS
APPLIED TO TREATMENT OF BREAST
CANCER
UP TO DATE CONCEPTS OF
TREATMENT
• TO TAKE THE LABORATORY
FINDINGS TO THE BEDSIDE AS NEW
DRUG THERAPIES—MAJOR
PROJECTS
• CHEMOTHERAPY KILLS CELLS
• IDEAL IS TO TREAT CANCER
WITHOUT KILLING NORMAL CELLS
TARGETED THERAPY
• A MONOCLONAL ANTIBODY THAT AIMS AT
EPITHELIAL GROWTH FACTOR—THE
DRUG HERCEPTIN..A TYROSINE KINASE
INHIBITOR..STRONGER ONES TO COME
(TYKERB,HERCEPTIN DM1).WILL WORK IN
HERCEPTIN FAILURES
• HSP-90 INHIBITORS .INHIBITS HSP-90
CHAPERONE FUNCTION ON ESTROGEN
TARGETED THERAPY
• ANOTHER MONOCLONALANTIBODY THAT
AIMS AT VASCULAR ENDOTHELIUM
GROWTH FACTOR IS CALLED AVASTINUSED IN COLON CANCER . IN BREAST IT
INCREASED TUMOR FREE INTERVAL BUT
NOT LIFE EXPECTANCY..MAY LOSE
APPROVAL BY FDA
• SERMS(SERUM ESTROGEN RECEPTOR
MODULATERS) (TAMOXIFEN AND EVISTA)
COMPETES WITH ESTROGEN FOR
ESTROGEN RECEPTOR FUNCTION
TARGETED THERAPY
• AROMATASE INHIBITORS-ATTACK
ENZYME THAT MAKES ESTROGEN
FROM TESTOSTERONE
• HEAT SHOCK PROTEINS ACT AS
CHAPERONES FOR ESTROGEN
RECEPTOR BREAST CA-NEW DRUGS
INHIBIT HEAT SHOCK PROTEINS
CELLULAR BIOLOGY AS
PROGNOSTICATOR
• PRESENTLY GENOMICS (ONCOTYPE
DX) IS A 21 GENE TEST USED IN
ER+/PR+ PTS FOR PROGNOSIS
• IN EUROPE 71 GENE TEST IS BEING
USED TO DEVELOP RECURRENCE
RISK(MAMAPRINT)
CELLULAR BIOLOGY AS
PROGNOSTICATOR
• KI-67 PROLIFERATION INDEX MEASURES
CELLULAR POTENTIAL FOR
DIVISION.HIGHER SCORE SHOWS
GREATER RECURRENCE
• DR, MARC LIPPMAN,MIAMI UNIVERSITY—
GENOMIC FINDING OF GREB 1,A GENEWHICH MEDIATES ESTROGENIC
STIMULATION ABILITY –ATTEMPT TO
SILENCE THIS GENE AS THERAPY OR
ESTABLISH RESPONSE TO HORMONE
THERAPY KNOWING VOLUME OF GREB 1
TYPE GENES
DCIS PROGNOSTICATOR
• IF P16,COX-2 AND K167 ALL
ELEVATED THERE IS A 5 TIMES
GREATER RISK OF RECURRENT
INVASIVE CANCER
• TRIPLE POSITIVE DCIS IS VERY
DIFFERENT FROM TRIPLE NEGATIVE
INVASIVE CANCER
CELLULAR BIOLOGY
• ALLOWS PTS TREATMENT TO BE
INDIVIDUALIZED I.E FOR MORE OR
LESS AGGRESSIVE TREATMENT
(SOME CASES MAY NOT NEED
CHEMO)
• NOW RECOGNIZE 5 SUBTYPES OF
BREAST CANCER WITH DIFFERENT
MOLECULAR CHEMISTRIES
. BR CA 1/BR CA 2
• MUTATED GENES OF BRCA1/BRCA2
CANNOT REPAIR DNA DAMAGE CELLS
• NORMAL CELL DNA REPAIR DONE BY
POLY ADP-RIBOSE POLYMERASE- (PARP’S)
• IF INHIBIT PARP’S WITH NEW
DRUG.(OLAPARIB)--THE PT WITH
BRCA/1BR/CA 2 WHO ALREADY HAVE THE
DEFECTIVE REPAIR…THE CANCER CELLS
WILL DIE
ENDOMETRIAL CANCER
GROWTH FACTORS
• M TOR INHIBITORS- BLOCK GROWTH
PATHWAYS IN ENDOMETRIAL CANCERS
• TRIAL OF ANTI-ANGIOGENIC DRUG
(AVASTIN ) TO BE DONE IN ENDOMETRIAL
CANCER
• A NEW AGE OF MEDICINE IS COMING