Nour G. Ali* ; Eman Abdel-latif , Raheem Hatem , Muhammed El-temsah , Waleed El-tokhy , Omar Ghoneim , Muhannad Mustafa.
Association of Egyptian-American Scholars
Background:
No doubt that cancer is one of the most dangerous and damned diseases all over the world from East to West due to lack of curative treatment that can end it drastically but , with the enormous efforts of scientists , we now have chemo , radio , targeted and endocrine therapy that can stop its danger partially. Tamoxifen (Tmx) is one of the most famous drugs in endocrine therapy for treatment of ER+ breast cancer clinically through the last 30 years.
Purpose:
Tmx is well-known to be one of the Selective Estrogen Receptor Modulators (SERMs) that can antagonist the estrogen hormone to bind to its receptor stopping by this pathway the effective role of estrogen in growing of cancer cells then mitotic division and there by reduction of carcinoma.
But the unknown is there are much more pathways for the active metabolites of tmx (N-desmethyltamoxifen and 4-hydroxytamoxifen) that enable to cause induction of cells senescence and appearance of apoptic marks not only in breast cancer ER+ but also in the negative status and Triple negative, some types of Leukemia , urinary bladder carcinoma , gastric carcinoma and the wonderful effect in sequestration of lung metastasis as well.
Methods:
We are 7 researchers that review 1151 scientific papers (2010-2015 with their old citations from 1991 to 2010) that were published in National Library of America that’s known with (Pub Med) online site about indications of tmx and its side effects , every 2 researchers were reviewing and filtering the papers together to insure correct and concentrate information and avoid faults as possible as we can.
Result:
We found that many pathways for tmx and its active metabolites are tested pre-clinically and clinically if 1) we used it in a higher dose than that’s used in current time in treatment of ER+ breast cancer clinically, 2) used with the usual certain chemotherapy protocols not alone. It will lead to introduction of senescence and growth inhibition as in AML and ALL, reducing of Multi Drug Resistance (MDR) by inhibition of P-glycoprotein 1 leading to a better effect in absorption of chemotherapeutic agents, also increasing the levels of ceramide , degrading Twist-1 protein that’s mainly responsible for cancer metastasis.
All of this leads perfectly to a better response for chemotherapy, increasing disease-free survival and all-over survival.
Conclusion:
Tmx deserves to have a much more pre-clinical and clinical experiments to find out its pathways and explore the other unknown pathways that may make us live one day without cancer.
This article was published in 3alamaltanmya
sponsored by Future Builders International Academy
Led by Dr.Maha Fouad
