Monthly Archives: June 2011

ASCO: A shift in thinking on causes of metastasis?

It’s easy to get lost in the sea of abstracts and presentations at the annual meeting of the American Society of Clinical Oncology (ASCO).  The amount of data being presented is overwhelming, with 30,000 people milling from halls to exhibits to poster sessions, trying to take it all in.  But what makes it easier for me is to keep an eye out for what is really sounding different or new, and what could have a major impact on the course of breast cancer for women.  Not the drug studies hyped in the media or at the fancy pharma exhibits, not the association studies on the posters, but what really has the potential to change the course of breast cancer for women? 

There has been a lot of talk in the media about the focus on personalized medicine at this year’s meeting here in Chicago – finding out the genetic fingerprint of a tumor and finding the drug that will match up with the patient’s tumor.  Sophisticated science, yes, a boon for pharmaceutical companies, yes, but great for patients?  Not so much.  These high tech, targeted treatments are adding months, not years to patients lives, at great expense.   Focusing only on the genetic drivers of tumors is not enough.  Cancer, particularly advanced cancer, usually finds a way to work around any of the road blocks thrown its way.  More mutations and resistance are almost always inevitable.  We need something more, a different approach.  We need to cut cancer off at the knees before it gets threatening at all.

The presentation that picqued my interest the most as possibly opening the door to something game changing was a presentation by Dr. Robert Weinberg of the Whitehead Institute for Biomedical Research.  His talk was entitled The EMT and the pathogenesis of high-grade carcinomas.  He spoke of new insights from his lab and others on how cancer may come to eventually metastasize and take lives, and how the biological changes that are occurring may be foreshadowed extremely early on, like maybe 30 to 40 years before the cancer causes death.  Dr. Weinberg presented data to show that differentiation of the cells very early on determines their future metastatic potential.  An idea that goes against conventional thought.  It may not be because of genetic mutations occurring late in the stage of cancer, as many believe and where much of the research is currently focused.  His theory is that the cell of origin plays a role in determining future tumor morphology and behavior.

And his second point was that the interaction between the cancerous cells and the surrounding tissue or stroma also plays a crucial role in the development of metastases.  Signals from the surrounding tissue cause some of the cells to undergo changes, a  biological program, called the epithelial-mesenchymal transition (EMT).  This transformation, he said, causes cells to take on traits that make them highly malignant, such as increased motility, invasiveness, and heightened resistance to apoptosis or cell death.  These changes make the cells like stem cells, cells that can self renew.  It is these cells, Dr. Weinberg speculates, that lead to metastatic growth of tumors. 

Most importantly, Dr. Weinberg showed convincing data to indicate that current cancer treatments aren’t effective against these cells that have undergone the EMT transformation, becoming more deadly.  Traditional chemotherapy agents are effective at wiping out the non-stem cell like cancer cells, but not those that have taken on the traits necessarly for self renewal at distant sites.  This could help explain the reappearance of cancer after dormancy, and the eventual spread of disease after removal of primary tumors.   Dr. Weinberg also showed data to indicate that non-stem cell like cells have the ability to spontaneously go through the EMT process and become stem like.  The implication for effective treatment of cancer, he emphasized, is that treatment must address both stem cells and non-stem cell like tumor cells.

I hope that some other laboratory groups and those in industry shift some resources toward following this line of thought – it makes sense based on what we now see happening to patients with cancer, and it provides a game changing possibility for really curing people of the disease.  That is an exciting possibility.