Thursday, March 8, 2012

Personalized Oncology? Congratulations, you have 20 different cancers!

Has anyone followed the literature on these companies that offer personalized genetic testing to customize oncologic treatments? In a recent study published in the NEJM a thought that has launched millions of Venture Capital Ships has encountered some very rough waters.

In fact I know of one Consumer Genetics founder whose "Second Pivot" was this whole theory of personalizing cancer therapeutics to a series of genetic tests.  A simple premise you see. One cannot characterize the molecular activity and weaknesses of a tumor through a microscope. With staining, you can see some insight but not all. Thus, you need to molecularly profile your cancer. 

The solution, we create an amazing molecular lab to take your tumor sample and "Personalized Treatment" based on our tests. Just make sure you get the tumor sample.

Simple enough to do one would think.

Except when you have multiple different tumors at multiple different sites. Worse yet, what if in the same sample you have different tumors?

Well, there is a flaw in the business plan.......

Enter March 8, 2012. "63 to 69% of all somatic mutations not detectable across every tumor region" Quote from NEJM Further "Mutational intratumor heterogeneity was seen for multiple tumor-suppressor genes converging on loss of function"

Ok, before you start the shorting and divestiture......

1. This was only in Metastatic Renal Cell Carcinomas
2. This is only in four patients
3. This can be mitigated if you take multiple tumor samples and sequence multiple areas, I hope.

What does this mean really? Something that in our heart of hearts we already suspect we know. Once cells become cancerous and mutate, they are more likely to mutate more.  Why would they be restricted in their mutations over time?

The Sherpa Says: You can really personalized a tumor's treatment by removing the entire tumor. If you can't do that, you risk missing personalization by 50%.


Red Herring said...

Yes, this is important news. Thanks for featuring it on your most excellent blog.

But haven't we known this for years? Many neoplasms are well known to have bizarre and variegated aneuploidies on routine cytogenetics, and CGH (in its original incantation) corroborated this. We have known for decades that cancer may begin as a clonal event but hates to play by our rules, clonal or otherwise. Why then do we so glibly slip on our "personalized medicine" goggles (closely related to "beer goggles") when the thrill of either profit or fame is on the line? Medicine, including genetic medicine, demands more and forgives less.

Steven Murphy MD said...


Yes, the hype starts with need for funding and follows with need for venture capital investment and then ends with PR/Marketing hype to give investors a return, regardless of the success of the company!

Anonymous said...

Yes, marketing personalized cancer care in this way is somewhat close to selling snake oil. Complete characterization of cancer in a person can conceivably be done, but would depend on technology that we don't quite have yet.

However, one point in favour of personalized cancer care today: it is already possible to make positive statements about a person's cancer, such as "We have found at least one clone in the tested tissue sample that is resistant to drug X", which can already be a useful thing to know.