Download part 1

Calculus and Cancer Drug Development
Studies
Stephan Gysin, PhD
UCSF Helen Diller Family Comprehensive Cancer Center
The Problem: Human Pancreatic Cancer
Challenge of the 21st century
4th leading cause of cancer deaths
33’000 people with pancreatic cancer die each year in the USA
Cancer is usually detected late during progression
Patients often refractory to any surgical treatment
Radiation and chemotherapy often not very rewarding
Markers/tools for early detection are missing
The pancreas is a gland:
Exocrine: releasing digestive
enzymes into the
duodenum
Endocrine: injecting
hormones into the blood (e.
g. insulin)
Pancreatic Ductal Epithelial Cells
Model: Pancreatic cancer
develops in a multistep process
normal pancreatic duct
PanIN-1A
PanIN-1B
PanIN-2
PanIN-3
Distinct stages of pancreatic cancer development
The end product is an aggressive
cancer.
adenocarcinoma
taken from R. Hruban at Johns Hopkins
Properties of cancer cells:
Capacity to divide continuously
Bypass pathways that lead to cell death
Attract and trigger the formation of blood vessels (angiogenesis)
Capacity to migrate and invade different organs (metastasis)
The driving force for these properties are mutations that accumulate over time.
Cancer cells are genomically instable, i. e. they constantly acquire mutations that
allow them to adopt mechanisms for uncontrolled growth.
Oncogenes: Genes that when mutated drive and accelerate cancer progression
Tumor suppressors: Genes that stop or slow down cancer progression; cancer
cells acquire mutations in tumor suppressors that functionally inactivate them.
Clusters of pancreatic cancer cells
Pancreatic cancer
cell lines in
culture
Highly metastatic variants
Metastatic
variants show
different
phenotype
Normal Cells
Oncogenes
Tumor Suppressors
Cancer Cells
Signaling
Proliferation
Migration/Invasion
Survival
Angiogenesis