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By Calla Cofield
Physicists are assisting in the fight against cancer in a variety of ways, as illustrated by two examples that were presented at the APS March Meeting. Krastan Blagoev, director of the Physics of Living Systems program for the National Science Foundation, is applying theoretical physics knowledge to the analysis of clinical cancer data, and is working on a program to bring these two groups together. Lydia Sohn, at the University of California, Berkeley, is developing new techniques for cancer detection and imaging, while studying the fundamental mechanics of cancer cells.
The National Cancer Institute has already invested in bringing physicists together with cancer researchers. In 2009 the NCI established 12 Physical Sciences Oncology Centers at major institutions throughout the US (as reported in the March 2010 APS News). According to the PSOC website, “by merging the physical sciences with cancer biology and oncology, NCI aims to accelerate the pace toward a cure.”
At a press conference at the APS March Meeting, Sohn showed reporters images that looked vaguely like shots of the night sky: speckles of light scattered against a dark blue background–a vast frontier to be explored. In this case, those bits of light are fluorescent markers attached to a particular type of biomarker called CCR7 that appears on the surface of breast cancer cells. CCR7 is of particular interest to cancer researchers because its high expression is associated with lower survival rates among patients. Sohn and her group are the first to attempt to map the spatial distribution of those markers on the surface of breast cancer cells.
To individually image the receptors, Sohn and her group used a technique called STORM (stochastic optical reconstruction microscopy), developed by a group at Harvard led by Xiaowei Zhuang. STORM allows the user to stack images of the same sample area, and reconstruct them into a 2-D or 3-D image with nanoscale resolution. In Sohn’s research this means looking at individual biomarkers to study their distribution. Now Sohn and her group will grow breast cancer cells in different microenvironments. The group would like to find out how mechanical forces and chemical cues change the spatial distribution of markers like CCR7, and eventually understand how their presence is linked to patient survival rates.
“Right now we have no idea what the spatial resolution will tell us, because no one’s had the opportunity to do this,” said Sohn in an interview. “But I think it’s going to tell us something; I think you should check back with me in a month.”
Sohn did her PhD work at Harvard working on superconductivity. She says her background and her training have proved valuable as she pursues the grand challenge of fighting cancer.
“What I’ve always brought with me when I’ve been working in the bio arena is the techniques that we use,” she said. “Whether it is actually doing lithography, making devices, to actually how we take measurements. And I think what we’re bringing in is a very quantitative technique, quantitative way of looking at things. In the end, the biologists still know how to do it best, but physicists bring new and innovative things to the table.”
Sohn is an applied physicist, tackling cancer from the laboratory. Krastan Blagoev is a theoretical physicist working on cancer via the clinic.
Blagoev is director of the Physics of Living Systems program at NSF. According to the program website, the Physics of Living Systems supports research with a focus on “understanding basic physical principles that underlie biological function.” He is also a theoretical condensed matter physicist by training. In a press conference at the March Meeting Blagoev, speaking as an individual, argued that theoretical physicists can not only be helpful, but might even be necessary to unearth the driving forces behind cancerous tumor growth.
Blagoev and colleague Tito Fojo, a medical oncologist in the Center for Cancer Research at the NCI, are analyzing data from clinical trials in oncology in order to study tumor growth. Most clinical data shows tumors under the influence of trial drugs, but when tumor cells become resistant to a drug, normal tumor growth may begin again. These growth rates are recorded in the data until the patient is removed from the trial. That window of natural growth rate provides the data Blagoev and Fojo want to study.
The growth rate of tumors depends on the characteristics of cancer stem cells (although whether or not these cancer cells are technically stem cells is still not clear). A linear rate of tumor growth would suggest that cancer “stem cells” share characteristics with adult stem cells, which divide into a single stem cell and a second progenitor cell that produces only a few generations of daughter cells before dying off. Exponential tumor growth suggests that the cancer cells are dividing more like embryonic stem cells, into two new cells that survive long-term and continue to divide. The indication–a faster rate of tumor cell production–is grim. It is these “dividing cancer cells” as Blagoev labels them, which would need to be targeted with new therapies.
The next step in evaluating this theory is to show that this exponential growth occurs across all patients. Blagoev says he has found a technique to rescale patient data into a single analysis. He is preparing his results for publication.
Theoretical physicists specialize in the analysis of complex systems, and can provide unprecedented expertise in data analysis. Blagoev also believes that because of the complexity of cancer–the incredible variety of cells that can arise even in a single patient–that a physics approach might help identify more fundamental drivers behind cancer behavior.
“This idea of creating simple theories is the essence of physics,” said Blagoev. “I think that what physics can bring here is to try and find common things rather than the differences between different cancers. We sort of have to forget about the details and look at the forest.”
Now Blagoev wants to start a program to bring theoretical physicists interested in cancer research together with clinical cancer researchers and oncologists, to share ideas and develop project proposals. Blagoev says he is waiting to find a mechanism to make the program a reality.
“It seems to me, based on my experience and what I know of the work of others, that there is a big need for theoretical physicists to enter the labs of clinical oncologists to work with them, and look at the data that’s never been published but that’s available in their labs. We’re looking for people who would be interested to come for 5 or 6 days and actually spend 8 to 10 hours a day working with colleagues from the other field to develop ideas,” said Blagoev. “In my experience, when clinical oncologists work with theoretical physicists I think they understand the power of quantitative thinking in terms of simple models. And they see the value this can have to cancer research.”
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