John Pepper, U. Arizona, "How to avoid acquired drug resistance to cancer"

Paradox of standard cancer therapy:

• Killing cancer cells does not necessarily promote health

We need alternatives to cytotoxins.  They impose strong selection, which causes harm in the long term

Cancer cells thrive by modifying their microenvironment, with shared secreted molecules that increase the fitness of both producer and consumer.

• Entail a cost to producer, but
• ...not evolutionarily robust
• idea: attack these targets

Shared secreted molecules

• angiogneisis factors
• secreted growht factors
• secreted invasion factors (MMPs)
• secreted immune factors...
• others...

 Why will this work: avoids drug resistance by disruption cooeperations, instead of trying to kill individual cells...

• These factors are not strongly selected for (?), since they confer a cost to producers, though are beneficial to the tumor as a whole

Take home points

• Killing cancer cells is not the only/best way to reduce morbidity/mortality
• Alternatives
• Blocking angiogeneisis
• Blocking acidosis
• Blocking motility and invasion

Problem:

• Blocking angiogenesis: can cause cancers to come back strong (according to some 

Critical assumption

• Cancer cells are related to each other through mitosis (as opposed to reprogrammed epithelial cells)
• Evidence from Simon Tavare, Shibata, et al.

Others:

• Tumor cells may recruit cancer cells in the blood stream (e.g., from metastatic tumors, or metastatic tumors may recruit blood-born cells from the primary tumor)