Speaker: Lydia Bilinsky,
Department of Mathematics and Statistics,
ASU,

Title: Chemotherapy and cellularlevel natural selection in tumors

Abstract: Traditional chemotherapy works by damaging the DNA of cancer cells, in the hopes that this will induce them to undergo apoptosis. However, cancer cells frequently have an impaired apoptotic reponse, as well as impaired repair mechanisms. Because of this, traditional chemotherapy has the dangerous sideeffect of breeding mutant cells. Natural selection within the tumor then results in the evolution of more aggressive cancer cells. In our work, we have investigated the competitive dynamics among idealized cancer phenotypes which differ in their effective division times and in the integrity of their apoptic and repair mechanisms. We have determined the “winner” phenotype for various treatment regimes which differ in the intensity and frequency of DNA damage. In addition to our results on the specific problem of cancer evolution, we have come to some interesting conclusions about the use of ODEs to model cellular division.

Speaker: Steffen Eikenberry
Department of Mathematics and Statistics,
ASU,

Title: Chemotherapy and cellularlevel natural selection in tumors

Abstract: Malignant melanoma is a cancer of the skin arising in the melanocytes, pigment producing cells found along the border between the epidermis and dermis. Melanoma undergoes two primary clinical phases - radial growth melanoma (RGM) characterized by radial spread through the epidermis, and vertical growth melanoma (VGM) characterized by vertical invasion into the dermis and angiogenesis. The most common treatment for melanoma is surgical excision of the primary tumor. This excision includes a margin of apparently healthy tissue intended to reduce the chance of recurrence caused by surviving cancer cells. Melanoma has a strong tendency to metastasize, and a phenomenon has been observed where metastases begin growing aggressively following removal of the primary tumor. In this talk we present a mathematical model of melanoma invasion into healthy tissue considering multiple tumor cell strains and an immune response. We then use this model to run a number of numerical experiments of primary tumor invasion and treatment by surgical excision. Through numerical investigation we found that in surgical treatments the margin of healthy tissue that must be excised to ensure that cancer will not reoccur due to the growth of surviving primary tumor cells is relatively small. To examine the phenomenon of metastasis growth following surgery we performed a set of experiments in which small metastases were created near the primary tumor. The immune response directed against the tumor typically destroyed these or held them to a very small size. However, if the primary tumor was excised most of the immune cells attacking it were also removed. This allowed metastases that had been previously been held in check to begin growing at a rapid rate and led to recurrence where total cancer mass increased more rapidly than in primary tumor invasion, representing a clinically much more dangerous cancer.