Friday, November 8, 2019

Contributions of Physics To Advancing Cancer Research Have Been Profound

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Human cancer (fibrosarcoma) cell studied at Johns Hopkins University Physical Sciences -Oncology Center for identifying metastatic agents.

It was two years after I received my first cancer treatment (at UCSF) using its high dose rate afterloader, see account here:

The Longest Day...And Then Some...

That I learned how advanced physics was contributing to the study of cancer and improving our understanding, mainly via PS- OC (Physical Science - Oncology  Centers) at different universities. Their origin goes back to 2009 when a dozen PS-)Cs were created by the National Cancer Institute. Their purpose was to team physical scientists with biologists and oncologists to seek a new understanding of cancer development.  This in turn could lead to new and improved treatments as well as diagnostics.  In the words of Paul Davies - a cosmologist who is the lead investigator at Arizona State University's PS-OC: (PT, Nov., 2014, p. 23)

"Cancer research is far too much money chasing far too few ideas. We need to think our way to a solution, not spend our way to a solution."

Davies then goes on to observe that both experimental and theoretical physics are useful in understanding and modeling metastasis.  At ASU one such synergistic project requires cancer cells to transition from static to slippery and motile, then squeeze through the tissue around the rumor and secrete membrane -dissolving chemicals to get into the bloodstream.

Once that occurs then other organs can be colonized and full metastasis is underway.  For example, in prostate cancer - which I have dealt with for 7 years now (latest PSA held steady at 4.8 from 6 months earlier) -   once the cancer cells get into the bloodstream they often migrate to the bones and especially the spine, where they become "mets". e.g.

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PET  scan of patient with advanced prostate cancer showing extent of bone metastasis (dark spots) congregated in the spine and even brain.  These are actual prostate cancer cells that have migrated from that gland to these other, distal locations.

For the advanced prostate cancer patient the only way known to get a further lease on life is via hormone therapies. such as ADT (androgen deprivation therapy) which slows tumor growth by cutting off the cancer's primary fuel: testosterone.  Since the side effects can be horrific, i.e. constant brain fog and cognitive incapacity - memory loss, depression, gynecomastia, weight gain, diabetes, cardiac issues etc. it's regarded as a desperation, last resort option by many.   Given all of this it is easy to comprehend why figuring out the metastatic process is important in cancer treatments, diagnostics.

At ASU one project that's received attention concerns the use of atomic force microscopy to measure the degree to which cancer cells (like the fibrosarcoma cell shown at top) soften as the disease progresses. The approach entails obtaining the Young's modulus of the cancerous cells being investigated.

The Young's modulus is a dimensionless quantity in the elastic mechanics of solids defined as the tensile stress divided by the tensile strain, e.g.

Y  =  (F/A) /  (L/  L )

The tensile stress then (numerator) is the ratio of the external force acting F, to the area A.  The tensile strain is the ratio of the change in length L (the quantity Y is usually applied to wires) to the original length ( L o ).  In terms of the ASU experiments, the researchers - to get Y-  prodded the cancerous cells with the tip of the atomic force microscope. According to lead investigator Davies:

"That change in Young's modulus is critical to the whole metastatic process, the squeezing through gaps."

The takeaway? Limit the cancer cells ability to stretch themselves and "squeeze" (e.g. keep L  a minimum) and it might be possible to control metastasis.  As Davies adds:

"What has become abundantly clear the last few years is that the physical mircoenvironment can play a critical role in cell behavior. Just pressure forces or even shear stresses can affect gene expression."

Given all this, we certainly should expect much more cancer research funding to find its way to the physicists working at PS-OCs and now playing an equally important role to oncologists in extending our comprehension of cancer metastasis.

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