By Naser Al Wasmi, NYU Abu Dhabi Public Affairs
Wael Rabeh’s father was bedridden fighting cancer at its most aggressive stages for more than a year. His son’s hospital visits drew an unfortunate but all too familiar scene as the months went from one seemingly aimless experiment to another. His father endured an onslaught of powerful drugs aimed at eradicating the cancer as indiscriminately as it was destroying the parts of his body capable of staving off the disease. After 14 months, he lost the battle and now, Rabeh has dedicated his life to research that makes sure no one goes through what his father had to endure.
“He was a lab experiment; pharmaceutical companies are still trying to discover a therapy that is more specific to cancer with less toxic effects on normal cells. But the less specific they are, the more likely they are to destroy the body. We want to isolate cancer, and fight it on that front without affecting healthy tissues,” said Rabeh, an associate professor of chemistry at NYU Abu Dhabi.
Today, his research is focused on achieving that task, looking at how cancerous cells differ from normal cells. Both cancer and normal cells use glucose as the main fuel for growth, but cancerous cells metabolize glucose at a rate of up to 200 times more than that of normal cells. One approach of cancer therapy is to limit cells access to glucose, thus cutting off the ability of cancerous cells to grow. The problem, and the reason why the disease is so difficult to cure, is that the enzymes in both cancerous and normal cells were believed to metabolize glucose in the same way. So medicines that work by inhibiting enzymes from binding to the substrate are destroying cancerous cells at the same rate as other cells.
However, Rabeh and his team of researchers believe they have found a characteristic unique to cancerous cell’s enzymes used in metabolizing glucose. If proven, this would be the first step in developing cancer therapy that can inhibit binding to cancerous enzymes and thus significantly hampering cancers from spreading.
“My approach is to make targeted drugs, then I’ll know how to enhance or make my drug more efficient. Chemotherapy can't tell the difference between the cells, and if you just throw things on cells, you don’t know what else it’s destroying. So, having knowledge on the nanoscale can help you solve a big problem,” he said.
Early detection of cancer is among science’s best defense from a disease that claims one in every six deaths. Today, with the advent of scientific processes, scientists are able to better detect cancer. But detecting a disease that is so adept at cloaking itself as part of the body’s normal processes is tricky. Getting on the molecular level enables better detection and treatment. But fighting a battle on the nanoscale is finicky business despite rapid scientific breakthroughs. And for that, Rafael Yong-Ak Song is helping develop an arsenal capable of getting on cancer’s level.
“Essentially, I am a toolmaker but my tools are micro and nanoscale tools. Before we treat anything we need to detect it. So we’re developing a highly sensitive biosensing system to detect circulating tumor biomarkers through a simple blood test, known as liquid biopsy,” said the associate professor of mechanical and biomedical engineering.
Song is researching new tools to detect naturally occurring genes, molecules, or characteristics in blood streams that are highly correlated to the presence of cancer. His research on these biomarker detection tools would allow doctors to diagnose the onset of cancers with more sensitivity and accuracy.
Using these biomarkers, doctors could also detect the location and stage of cancer. Not only would it make the screening less invasive than the traditional biopsy, whereby doctors are required to surgically retrieve tissue samples, but it would also allow doctors to detect cancers that were previously inaccessible through biopsies.
“If you have lung cancer, how do you conduct a biopsy? No surgery allows you to do that, the same goes for brain cancer. You can’t do that. So if we have a liquid biopsy method, then we can potentially detect those cancer types that are inaccessible through traditional biopsies,” he said.
Furthermore, liquid biopsies would continue to allow doctors to monitor a patient’s status as they receive treatment without the constant pain and invasiveness of tissue biopsy. This approach would allow doctors to better assess cancer-treatment effectiveness and provide real-time data that could potentially uncover cancer cells susceptibility to new forms of treatment. Ultimately, the liquid biopsy method will lead to “personalized precision medicine” where every patient gets treatment at the right location with the right type and amount of drugs. That is Song’s vision of “future medicine.”
Diagnosing cancer and understanding the effectiveness of individual treatments is another front that needs more research. Cancer is a complex disease that requires a case-by-case approach. Developing a drug or combinatorial treatment with existing drugs needs testing, and doing that in a lab setting is problematic. Jeremy Teo, assistant professor of mechanical and biomedical engineering, uses biomaterials to engineer three dimensional cell cultures that mimic tumors and allow scientists to test treatments accurately without the need for live subjects.
“Aside from the ethical issues with mice models, there are inaccuracies because biological systems are so noisy. By building biomimetic tissues from the very fundamental building blocks, we try to eliminate the use of mice models and we get a better understanding of the mechanisms involved. So we can detect whether a certain drug is better than another and why. Instead of just blindly putting drugs in mice and seeing what happens,” Teo said.
Part of building this system allows Teo and his research team to create a drive representing various patients in miniaturized biomimetic cultures. This would allow scientists to screen and test the array of medicines available on mini ‘individual subjects’ without risk, or mice. And the individualized testing could even help doctors determine accurate dosage levels for each individual patient.
“Today, dosage is based on body surface area, not genetics. Everyone is different, we look the same but we are genetically different. So if we have a cancer drug that’s working well on an individual but not the other, we want to know why.”
Using these methods, doctors could ascertain optimum dosage. This would spare patients from being prescribed doses too low for them to overcome the disease or too high for them to endure.
Cancer treatment today is abundantly more effective than it was a decade ago, when Rabeh’s father was sick. For him, progress is bittersweet, as advances in the field have increased the survivability rate of those suffering from the ravenous disease. Had they been discovered before, Rabeh’s father and millions of others may have had a fighting chance.
“Will we in our lifetime find a cure? We’re not there yet, but we’re better,” Rabeh said.