To what extent do current treatments
address heterogeneity?
KP: I don’t think intratumor heterogeneity
has been that well-incorporated into clinical
practice yet. I think we’re still in the phase
of trying to understand it. Resistance and
recurrence happens because of heterogeneity.
In hematopoietic malignancies, you can
take blood and sequence the tumor cells, and
you see a clone that seems to be dominant.
But then after treatment, in a recurrence,
sometimes you have a clone that was not
even really present very much in the original
diagnostic sample but is some kind of earlierstage
clone. And so, during treatment, that
clone must have expanded and changed.
Using deep sequencing, you can see much
more of this heterogeneity. And of course
you have translocations that you can follow
at the single‑cell level.
JVF: From a clinical perspective, cancer is
a few hundred different diseases. But the
key question is what the genetic and epigenetic
underpinnings are. Certain cancers
begin with a single type of aberration like a
BCR‑ABL [breakpoint cluster region, c-abl