The microenvironment inside a tumor is extremely complex and adaptive, involving spatial and temporal variations in nutrient and waste gradients, cellular physiology, metabolism, the expression patterns of genes and proteins as well as the malignant progression. The sum of all these elements defines the response of a tumor to treatment. The multicellular tumor spheroid system has been a primary example of in vitro models of the tumor microenvironment, which has provided numerous insights into tumor dynamics and progression. We develop a multiscale model to study spheroid tumor growth, which includes at the subcellular level a protein expression network that controls the possibility for cell cycle arrest, and at the cellular level a hybrid of cellular dynamics (lattice Monte Carlo) and reaction-diffusion dynamics of chemicals (PDEs). This integrated subcellular and cellular model provides a realistic representation of both structure and dynamics over a large range of time and length scales. Our simulations show favorable comparisons with spheroid experiments. The combination of a data-rich experimental system with sophisticated mathematical modeling holds the promise of an improved basic understanding of malignant progression and therapeutic response in humans.
Tumor-induced angiogenesis is the formation of new blood vessels from existing vasculature in response to chemical signals from a tumor. Angiogenesis marks the pivotal transition from benign solid tumor growth to vascular growth, a more progressive and potentially fatal stage of cancer beyond which cancer becomes extremely difficult to treat, existing therapies become ineffective and survival rates decrease. Angiogenesis is a complex process, involving multiple time scales and intricate interplay between biochemical and biomechanical mechanisms, including cell-cell and cell-matrix interactions, cell surface receptor binding, and intracellular signaling pathways. The sequential morphogenetic processes required for angiogenesis to occur are well known and a review of these follows; however, what is still not completely understood is how cellular and molecular mechanisms are coordinated to control these processes. We develop a cell-based, multiscale modeling framework of tumor-induced angiogenesis designed to address these questions of mechanism. An understanding of the principal underpinnings driving angiogenic processes will advance efforts aimed at the development of new therapies for treating cancer and other angiogenesis-dependent diseases.
Chemotherapy is one of the most commonly used methods of cancer treatment, but most forms of chemotherapy are extremely toxic and take a heavy toll on the health of the patient. This is because many standard forms of chemotherapy target and kill cells in the process of division, an approach that destroys non-cancerous cells as well. Cancer patients undergoing chemotherapy suffer from hair-loss and compromised immune systems because both involves rapidly dividing cells. Still the full effects of chemotherapy are not completely udnerstood. By creating a better model of tumors, tumor growth, and the effects of chemotherapy upon such tumors, we hope to better understand tumor growth mechanisms and imporve treatments for cancer. During the semester from 9/05 to 5/06, a team of very talented undergrad students (Math Clinic) from Harvey Mudd College worked under the guidance of Lisette De Pillis, and modeled vascular tumor growth and chemotherapy. The team extended our avascular tumor model to include vasculature. The vascular tumor model simulated chemothreapy treatments using cyclophosphamide, a non-cell cycle specific anti-cancer drug.
Last modified: Tue Oct 30 12:33:26 MDT 2007