BREAST CANCER PREVENTION BY ENHANCING POSTLACTATIONAL INVOLUTION WITH CABERGOLIN...
INTRODUCTION AND PROBLEM TO BE SOLVED: BREAST CANCER IS THE MOST FREQUENT TUMOR IN WOMEN, AND ITS INCIDENCE WILL INCREASE DUE TO THE AGING OF THE POPULATION. CURRENT CHEMOPREVENTIVE DRUGS, SUCH AS ESTROGEN-RECEPTOR MODULATORS AND...
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INTRODUCTION AND PROBLEM TO BE SOLVED: BREAST CANCER IS THE MOST FREQUENT TUMOR IN WOMEN, AND ITS INCIDENCE WILL INCREASE DUE TO THE AGING OF THE POPULATION. CURRENT CHEMOPREVENTIVE DRUGS, SUCH AS ESTROGEN-RECEPTOR MODULATORS AND AROMATASE INHIBITORS, HAVE VERY SEVERE AND ANNOYING SIDE EFFECTS SUCH AS THROMBOEMBOLISM AND UTERINE CANCER. IT IS CRITICAL TO HAVE MORE SECURE CHEMOPREVENTIVE STRATEGIES. THE SOLUTION PROPOSED IN OUR PREVIOUS SAF-RETOS-2017 PROJECT: EARLY AND REPEATED PREGNANCY IS ASSOCIATED WITH BREAST CANCER PROTECTION. WE PROPOSED THAT THIS PROTECTION IS RELATED TO AN EFFICIENT POSTLACTATIONAL INVOLUTION. ENHANCING THIS PHENOMENON WITH DRUGS COULD BE AN ALTERNATIVE FOR CHEMOPREVENTION IN WOMEN SUSCEPTIBLE TO DEVELOPING BREAST CANCER, SUCH AS THOSE WITH HEREDITARY ANTECEDENTS OR PRIMIPAROUS WOMEN OLDER THAN AGE 35, AMONG OTHERS. PRELIMINARY RESULTS IN OUR PREVIOUS SAF-RETOS-2017 PROJECT: OUR PRELIMINARY RESULTS SHOW THAT BRCA1/P53-DEFICIENT MICE AFTER PREGNANCY HAVE INCREASED BREAST TUMOR LATENCY AND DECREASED INCIDENCE. ALSO, THE POTENTIATION OF POSTLACTATIONAL INVOLUTION WITH CABERGOLINE POTENTIATES THIS PROTECTIVE EFFECT. THEREFORE, WE PROPOSE THAT CABERGOLINE BE USED AS A CHEMOPREVENTION DRUG IN HUMANS IN A SINGLE DOSE JUST AFTER LACTATION. OBJECTIVES: WE DEMONSTRATED IN OUR PRELIMINARY RESULTS THAT ENHANCING POSTLACTATIONAL INVOLUTION IN AN IN VIVO MODEL WITH THE DOPAMINERGIC AGONIST CABERGOLINE INCREASES THE KNOWN PROTECTION PRODUCES BY PREGNANCY AGAINST BREAST CANCER. HERE, OUR OVERALL GOAL IS: TO ENHANCE THE POSSIBILITY OF ACHIEVING A PRACTICAL APPLICATION OF THESE RESULTS SO THAT CABERGOLINE COULD BE USED AS A PREVENTION STRATEGY AGAINST BREAST CANCER IN THE HUMAN POPULATION. TO THIS END, WE FIRST PROPOSE OBTAINING A PRIMARY PATENT OF OUR PRECLINICAL MODEL TO PROTECT THE RESULTS FOR THE FIRST YEAR, WHICH IS WHAT THIS PATENT MODEL ALLOWS (OBJECTIVE 1). DURING THAT YEAR, WE PROPOSE TO INCREASE THE VALUE OF THE INITIAL RESULTS AND THEIR INNOVATION VALUE (OBJECTIVE 2) THROUGH TWO SUB-AIMS: FIRST, KNOWING THE DESTINATION AFTER TREATMENT WITH CABERGOLINE OF THE PRETUMORAL INITIATED CELLS (SUB-AIM 2.1); THUS, WE HAVE ALREADY GENERATED BRCA1/P53-RFP (RED FLUORESCENT PROTEIN)-POSITIVE MICE. THUS, WE WILL TRACK RECOMBINANT BRCA1/P53-RFP-POSITIVE TUMOR-INITIATING CELLS (25% HERE) AND EVALUATE THEIR DESTINY. SECOND, BY VALIDATING THE PROTECTION OF CABERGOLINE IN THE HUMAN POPULATION THROUGH A MASSIVE RETROSPECTIVE EPIDEMIOLOGICAL STUDY ON DATA OF 5.6 MILLION PEOPLE (SUB-AIM 2.2). AFTER THE FIRST YEAR OF THE PRIMARY PATENT, WITH THE INCREASED INNOVATIVE VALUE OF OUR RESULTS, A BROADER PATENT WILL BE REQUESTED, WITH PCT (OBJECTIVE 1). THE NEW DATA AND THE BROADER PATENT WILL STRENGTHEN OUR POSITION WHEN CONTACTING POTENTIAL INVESTORS. THUS, WE WILL CONTACT INVESTORS, MAINLY COMPANIES THAT ALREADY PRODUCE CABERGOLINE AND ARE POTENTIALLY INTERESTED IN A SECOND USE (OBJECTIVE 3). WE HOPE TO HAVE CONVINCED INVESTORS TO CONTINUE TO SUSTAIN THE PATENT AND CARRY OUT THE FINAL MOMENTUM TO ARRIVE IN THE CLINIC AND THE MARKET DURING THE PROJECT. CONCLUSION: THIS PROPOSAL HAS IMPORTANT SOCIAL AND HEALTH IMPLICATIONS. WE TRY TO PREVENT BREAST CANCER WITH A NEW CHEMOPREVENTION STRATEGY WITH AN AFFORDABLE DRUG ONCE LACTATION IS COMPLETE AND WITH FEWER SIDE EFFECTS THAN THE ACTUAL ONES. THAT IS HOW WE TRY TO ANTICIPATE A HEALTH PROBLEM THAT WILL INCREASE IN THE NEXT FUTURE ONLY BECAUSE OF THE AGING RISK FACTOR. ANCER DE MAMA\INNOVACION\EPIDEMIOLOGIA\QUIMIOPREVENCION\EMBARAZO\CABERGOLINA\INVOLUCION POSTLACTANCIA
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