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Adaptive therapy utilizes competitive interactions between resistant and sensitive cells by keeping some sensitive cells to control tumor burden with the aim of increasing overall survival and time to progression. The use of adaptive therapy to treat breast cancer, ovarian cancer, and pancreatic cancer in preclinical models has shown significant

Adaptive therapy utilizes competitive interactions between resistant and sensitive cells by keeping some sensitive cells to control tumor burden with the aim of increasing overall survival and time to progression. The use of adaptive therapy to treat breast cancer, ovarian cancer, and pancreatic cancer in preclinical models has shown significant results in controlling tumor growth. The purpose of this thesis is to draft a protocol to study adaptive therapy in a preclinical model of breast cancer on MCF7, estrogen receptor-positive, cells that have evolved resistance to fulvestrant and palbociclib (MCF7 R). In this study, we used two protocols: drug dose adjustment and intermittent therapy. The MCF7 R cell lines were injected into the mammary fat pads of 11-month-old NOD/SCID gamma (NSG) mice (18 mice) which were then treated with gemcitabine.<br/>The results of this experiment did not provide complete information because of the short-term treatments. In addition, we saw an increase in the tumor size of a few of the treated mice, which could be due to the metabolism of the drug at that age, or because of the difference in injection times. Therefore, these adaptive therapy protocols on hormone-refractory breast cancer cell lines will be repeated on young, 6-week old mice by injecting the cell lines at the same time for all mice, which helps the results to be more consistent and accurate.

ContributorsConti, Aviona (Author) / Maley, Carlo (Thesis director) / Blattman, Joseph (Committee member) / Seyedi, Sareh (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Adaptive therapy is a novel up-and-coming cancer treatment strategy to minimize chemoresistance in cells to improve patient prognosis. The standard of care cancer treatment has a fixed linear approach known as Maximum Tolerated Dose (MTD) which promotes an exponential growth of resistant cancer cell populations in the tumor. Through this

Adaptive therapy is a novel up-and-coming cancer treatment strategy to minimize chemoresistance in cells to improve patient prognosis. The standard of care cancer treatment has a fixed linear approach known as Maximum Tolerated Dose (MTD) which promotes an exponential growth of resistant cancer cell populations in the tumor. Through this treatment procedure, a population of chemoresistant cells resurges, decreasing the survival in patients, and narrowing potential treatment options (Gatenby). An assortment of chemotherapeutic drugs and dosing schedules were tested on ER+ endocrine-resistant MCF7 breast cancer cells in an immunodeficient mouse model. After the cessation of treatment, some mouse models’ tumors remained stable or began to shrink. Several immunodeficient mouse models have indicated unexpectedly high levels of neutrophils stemming from an unknown origin. We aim to understand if neutrophils' innate immunity may affect tumor size post-chemotherapy treatment and if it has therapeutic implications along with adaptive therapy. MCF7 breast cancer tumors were extracted from the mice, embedded in wax, and sliced, and immunofluorescence was performed to detect neutrophils and nuclear components. Currently, the protocol is in its third round of optimization.
ContributorsMestas, Lauren (Author) / Maley, Carlo (Thesis director) / Richker, Harley (Committee member) / Marquez Alcaraz, Gissel (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2024-05