Abstract：
:The issue of resistance to targeted drug therapy is of pressing concern, as it constitutes a major barrier to progress in managing cancer. One important aspect is the role of stochasticity in determining the nature of the patient response. We examine two particular experiments. The first measured the maximal response of melanoma to targeted therapy before the resistance causes the tumor to progress. We analyze the data in the context of a Delbruck-Luria type scheme, wherein the continued growth of preexistent resistant cells are responsible for progression. We show that, aside from a finite fraction of resistant cell-free patients, the maximal response in such a scenario would be quite uniform. To achieve the measured variability, one is necessarily led to assume a wide variation from patient to patient of the sensitive cells' response to the therapy. The second experiment is an in vitro system of multiple myeloma cells. When subject to a spatial gradient of a chemotherapeutic agent, the cells in the middle of the system acquire resistance on a rapid (two-week) timescale. This finding points to the potential important role of cell-to-cell differences, due to differing local environments, in addition to the patient-to-patient differences encountered in the first part. See all articles in this Cancer Research section, "Physics in Cancer Research."
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kessler DA,Austin RH,Levine Hdoi
10.1158/0008-5472.CAN-14-0118subject
Has Abstractpub_date
2014-09-01 00:00:00pages
4663-70issue
17eissn
0008-5472issn
1538-7445pii
74/17/4663journal_volume
74pub_type
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