December 22, 2012 4 Comments
There are two types of cancer patients: those we can treat and those we can’t. As I reflect on this year and the years past during which we have applied the process of laboratory-guided treatment, I am reminded of this fact.
The EVA-PCD functional profile enables us to choose active treatments for patients, but I have sometimes wondered whether we are, in fact, choosing patients for the available drugs. While the end result may not be all that different, e.g. superior clinical outcomes over randomly administered (standard) therapies, the path to that outcome, leaves room for interesting discussion.
I first pondered this issue at the time of completion of our earliest study. That study was conducted in childhood acute lymphoblastic leukemia (ALL). Recognizing that the corticosteroids were among the most important drugs for ALL, we exposed freshly isolated lymphoblasts from ALL patients to dexamethasone (ex vivo). At the fourth day we measured the degree of cell death and separated the patients in “sensitive” and “resistant “ subgroups. Strikingly, those children whose lymphoblasts died in the laboratory following exposure to dexamethasone (ex-vivo), virtually all survived without relapse, while those children whose lymphoblasts did not die in the laboratory following dexamethasone exposure (ex-vivo) relapsed at an alarming rate with only 25 percent still alive at the sixth year of follow up (p=0.009).
What we had succeeded in doing by Day 4 of diagnosis was something that all the known prognostic factors, like age, WBC and male vs. female could not do, namely accurately identify the responders and survivors.
Today, when I test patients in our laboratory, I consistently double or even triple the response rates over standard protocols, yet a subset of patients are not found sensitive to the available therapies. Patients who do not respond to chemotherapy are today known, in the oncologic vernacular, as “failing therapy.” If we view these “non-responders” as a biologically distinct group (not unlike the dexamethasone-resistant ALL patients above) then our role, in the field of functional profiling, is to quickly segregate the responders (to available drugs) from the non-responders and move those “non-responders” immediately to something that will work for them. In this light, patients no longer “fail therapies” but instead “therapies fail patients.” It is then our mandate to use the ex-vivo platforms to find (and yes, discover) novel therapies and combinations that will meet their unmet need.
As the New Year is upon us I am filled with the expectation that 2013 will be one of discovery and innovation. Never before have so many interesting compounds been available for study. If we are fortunate enough to succeed in our efforts to collaborate with members of the drug development community and have the opportunity to intelligently apply functional profiling, for drug discovery, 2013 could be a very good year indeed.