Cancer is a disease acquired through mutations which leads to uncontrolled cell division and destruction of normal tissue within the body. Recent increases in available cross-species data of cancer in mammals, reptiles, birds, and other vertebrates has revealed that the prevalence of cancers varies widely across species. Life-history theory suggests that there could be traits that potentially explain some of that variation. We are particularly interested in species that get very little cancer. How are they preventing cancer and can we learn from them how to prevent cancer in humans? Comparative oncology focuses on the analysis of cancer prevalence and traits in different non-human species and allows researchers to apply their findings to humans with the goal of improving and advancing cancer treatment. We incorporate the predictions that animals with larger bodies have evolved better cancer suppression mechanisms than animals with small bodies. Ruminants in the past were larger in size than modern day ruminants and they may have retained cancer defenses from their large ancestors. The strong cancer defenses and small body size combined may explain the low prevalence of cancer in Ruminants. This paper aims to evaluate the presence of benign and malignant neoplasia prevalence across multiple ruminant species following a time of dramatic decrease in body size across the clade. Our aim is to illuminate the potential impact that these shifts in body size had on their cancer prevalence as well as test the statistical power of other key life history variables to predict cancer prevalence.
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.
The risk of developing cancer should theoretically increase with both the number of cells and the lifespan of an organism. However, gigantic animals do not get more cancer than humans, suggesting that super-human cancer suppression has evolved numerous times across the tree of life. This is the essence and promise of Peto’s Paradox. We discuss what is known about Peto’s Paradox and provide hints of what is yet to be discovered.
Surveillance of Barrett’s oesophagus allows us to study the evolutionary dynamics of a human neoplasm over time. Here we use multicolour fluorescence in situ hybridization on brush cytology specimens, from two time points with a median interval of 37 months in 195 non-dysplastic Barrett's patients, and a third time point in a subset of 90 patients at a median interval of 36 months, to study clonal evolution at single-cell resolution. Baseline genetic diversity predicts progression and remains in a stable dynamic equilibrium over time. Clonal expansions are rare, being detected once every 36.8 patient years, and growing at an average rate of 1.58 cm[superscript 2] (95% CI: 0.09–4.06) per year, often involving the p16 locus. This suggests a lack of strong clonal selection in Barrett’s and that the malignant potential of ‘benign’ Barrett’s lesions is predetermined, with important implications for surveillance programs.