In 2014, the skeleton of a young man — dated to 1200 B.C. — was unearthed in northern Sudan. The well-preserved holes riddled his bones, indicating the earliest confirmed case of cancer.
Cancer has taken millions of lives since then, but humanity is learning to fight back. As part of this struggle, Connor McGuigan ’20 has been researching ways to prevent metastasis, cancer’s most deadly form.
Working under Pragya Shah grad at the Lammerding Lab, McGuigan conducts research investigating the relationship between a cell’s ability to repair DNA, its deformability and how those two characteristics contribute to cancer.
Although the word “cancer” calls to mind a single tumor growing in the body, cancer’s deadly power is actually derived from metastasis — its ability to move away from its initial site to other places in the body.
“Metastasis is the number one leading cause of cancer deaths. Ninety percent of patients that have metastatic stage four cancer end up dying from their disease, so it is a huge area of research for clinicians and scientists alike,” McGuigan said.
According to McGuigan, in a case of metastatic cancer, treatment becomes significantly more difficult. Instead of being concentrated in one area, radiation therapy must be applied to multiple parts of the body — or even the entire body — killing many healthy cells in its attempt to kill cancerous ones.
Although most cancer research is preventative or treatment-oriented, McGuigan’s research uses biomedical engineering and mechanics to approach the issue. Since metastasis involves cancer cells physically breaking off from the initial tumor and spreading to other places, McGuigan has worked to model cancer cell movement.
McGuigan and others at the Lammerding Lab use devices made of polydimethylsiloxane, a hard gelatin-like substance, to replicate the tight constrictions found in pores lining blood vessel walls. Systems like the lymphatic or circulatory system offer a perfect route for cancer cells in the body.
By sending cells through the PDMS devices, researchers can determine the structural consequences of passing cells through small openings. This can help predict how well cancer cells penetrate blood vessel walls.
McGuigan discovered that mouse tissue cells with a forced ataxia telangiectasia deficiency — removed chemically or through gene modification — have up to 40 percent lower lamin levels than regular mouse tissue cells.
According to McGuigan, this suggests that cancer cells, which have lower ATM levels, might also have this lamin deficiency. If cancer cells have a consistently lower lamin level than healthy cells, it might explain why cancer cells can easily penetrate blood vessel walls and form secondary tumor sites in the form of metastasis.
While the discovery of the lamin-ATM relationship is promising, McGuigan says there is still work to be done.
McGuigan hopes to further test on cancer cells, which do not all have ATM deficiency, in order to see if these cancer cells also have lower lamin levels. This would confirm or reject the supposed protein correlation.
The Edwin Smith Papyrus, dated to 3000 B.C., is humanity’s oldest written description of cancer. Its section on the disease ends with the simple phrase: “There is no treatment.” Although cancer has resulted in many lives lost, research like McGuigan’s has contributed to many lives saved, by both identifying and treating one of humanity’s oldest diseases.