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.

In 1997, physicians and researchers Ambre Olsen, Virginia Smith, John Bergstrom, Joyce Colling, and Amanda Clark published, “Epidemiology of Surgically Managed Pelvic Organ Prolapse and Urinary Incontinence,” in the journal Obstetrics and Gynecology. In their article, the authors retrospectively analyzed data from patients who underwent surgery for pelvic organ prolapse or urinary incontinence two years prior in 1995. Often due to a weakening of or damage to their pelvic muscles, women with pelvic organ prolapse can experience a descent of pelvic organs into the lower pelvis and vagina. People with urinary incontinence can experience bladder control issues and urinary leaks. According to the authors, an estimated fifty percent of women who have previously given birth have had a prolapse. In their article, Olsen and colleagues analyze factors such as race, age, and weight in women who had surgery to treat pelvic organ prolapse and ultimately advocate for a standard assessment for the severity of those conditions.

In 1996, a team of researchers associated with the International Continence Society published “The Standardization of Terminology of Female Pelvic Organ Prolapse and Pelvic Floor Dysfunction” in American Journal of Obstetrics and Gynecology. Pelvic organ prolapse is characterized by the descent of the pelvic organs into the lower portion of the pelvis and is often caused by a weakening of the muscles and ligaments that normally hold the organs in place. The authors concluded that physicians and researchers needed to develop a system of standardized terms to use to describe the anatomical position of pelvic organ prolapse in women. They propose using terms that emphasize the location of the prolapse rather than just the involved organ. They also suggest that the system utilizes a series of examinations and imaging to uniformly describe and quantify pelvic organ prolapse. The article by Bump and colleagues was one of the first to call for a standardized system using specific terms to communicate findings about pelvic organ prolapse systematically across clinical and academic research settings.

In 1983, researchers Alan Trounson, John Leeton, Carl Wood, Mandy Besanko, and Angelo Conti published the article “Pregnancy Established in an Infertile Patient After Transfer of a Donated Embryo Fertilized In Vitro” in The British Medical Journal. In the article, the authors discuss one of the first successful experiments using in vitro fertilization, or IVF, with the use of a human donor embryo at the Monash University and Queen Victoria Medical Center in Melbourne, Australia. Prior to the article’s publication, it was uncertain whether scientists could successfully use human donor embryos in IVF techniques. Although the pregnancy ended in a miscarriage ten weeks later, it showed that IVF was possible for those who needed to use someone else’s donated egg cells. Trounson and his colleagues’ paper provided a basis for future IVF pregnancies using donated embryos and helped develop a treatment option for men and women who could not conceive through sexual intercourse alone.

On 29 September 1973, researchers David De Kretzer, Peter Dennis, Bryan Hudson, John Leeton, Alexander Lopata, Ken Outch, James Talbot, and Carl Wood published “Transfer of a Human Zygote,” in The Lancet. In the article, the authors describe an experiment that resulted in one of the first pregnancies established via in vitro fertilization, or IVF. Prior to the article’s publication in 1973, there was no published evidence demonstrating whether IVF treatment would work in humans, although evidence existed showing that IVF worked in other mammals for breeding purposes. At the end of the article, the authors state that the embryo failed to implant into the wall of the patient’s uterus, leading to a miscarriage less than a week after the authors found evidence of pregnancy in the patient. The authors of “Transfer of a Human Zygote” were some of the first researchers to perform IVF, although unsuccessfully, which contributed to the overall understanding of IVF as an emerging technology.