When I was accepted into Fred Hutch’s Pathway Explorers program, I honestly was scared and nervous. I came into the program thinking it would be a formal and serious environment. Having a rather basic understanding of cancer research, I didn’t know what to expect. But I was met with the complete opposite. The Fred Hutch community is a welcoming space where I was able to meet new people from various backgrounds that came together to learn about science. One of the most defining moments of my experience was Dr. Eric Scott Nealy’s presentation. He currently studies Pediatric Brain Cancer in the Olson Lab at Fred Hutch. First, he notes cancer as not just one type of disease. He says each type is driven by genetic mutations in genes unique to that cancer type. The brain is a very complex organ, which makes tumor treatment a challenge. With the complete elimination of tumor cells, there is a risk of brain damage or disability. But with incomplete tumor removal, the patient could face recurrence or metastasis. When Dr. Eric Scott Nealy first explained his work as a “roach motel,” I was intrigued. He wants to use chemokine gradients to lure Pediatric Brain Tumor cells into a local “immunotherapy” trap. Chemokines are small signaling proteins that play a key role in development, immune cell trafficking, and cancer metastasis. More invasive brain tumors express more chemokine receptors. He breaks his project down as: Cancer biology (bait) plus Immunology (poison) leads to Chemical engineering (trap). “The bait” he describes as utilizing chemokine gradients to lure PBT cells. “The Poison” he describes as blocking “don’t eat me signals” on PBT cells to permit white blood cells to attack them. And most importantly “The Trap” is a non-toxic gel that serves as a centralized location for luring and eliminating PBT cells in the brain. Testing this on mice displayed a promising result, attenuated tumor growth for two weeks. This presentation was a highlight because it truly shows that science has many “rabbit holes” and motivation is key to surpass them. Dr. Eric Scott Nealy’s presentation made me realize that approaching a disease requires multiple types of science. It is truly a team effort. It also requires one person with an idea and others willing to pick up their idea and grow with it. Who knows, maybe one of us could be the future of his project!
Chemokine gradients luring PBT cells into the trap vs. no chemokine lure
Broccoli could be the future of chemoprevention. A vegetable many hate is soon to be a superhero in the world of cancer research. This is what Dr. Thomas Kensler, a toxicologist and translational researcher at Fred Hutch, has concluded. He and his team work to develop strategies to protect against unavoidable exposures to environmental carcinogens in the air, water, and food. For decades, Dr. Thomas Kensler has been on a never-ending mission to find a way to conduct a cancer-inhibiting process that’s sparked when you eat cruciferous vegetables such as kale, cabbage, cauliflower, and most importantly, broccoli. His guiding question: “Can people be protected from unavoidable exposures to environmental carcinogens by increasing their rates of detoxications and facilitating the elimination of these carcinogens from our body?” The answer is yes, and the key is broccoli pills. Kensler’s research started when he went to the rural Qidong region of China to help reduce the high rates of liver cancer in the area. They mandated corn farmers there to grow corn that contained a carcinogen known as aflatoxin. Kensler and his peers wanted to find a way to stop aflatoxin’s carcinogenic process by chemoprevention. They found a way through cruciferous vegetables, more specifically broccoli. Since toxins are fat soluble, when they enter the body, they become trapped. To detoxify harmful chemicals, the body attaches a molecular chain which could make the chemical more reactive. This might lead to mutations. The goal is to be able to make this molecular chain, then quickly couple it with sugars or amino acids using more enzymes to make this chemical unreactive. This would lead to eventually making this toxin water-soluble, which is the goal. The liver struggles in detoxifying these chemicals, but Kensler’s research shows it is possible to help the body by using chemicals found in broccoli. Cruciferous vegetables, like broccoli, have phytochemicals called glucosinolates. When you consume broccoli, it sets off a chain reaction between one of these glucosinolates and the enzyme myrosinase, found when broccoli is chopped or damaged. When these two compounds are mixed, it creates the plants' natural defense mechanism. Kensler’s broccoli supplements target the body’s cellular defense mechanism, the Keap1-Nrf2 pathway, leading to the transformation of fat-soluble toxins into stable molecules that are water-soluble. In other words, our own bodies will flush away these carcinogens. Because of China’s economic and social revolution, liver cancer rates decreased. But shortly after, it spiked again because of smoking and air pollution. Kensler realized the principles he applied for aflatoxin could also be used to combat air pollution. Kensler and his team were able to increase the elimination of carcinogens from test subjects by 67%. In December 2019, Kensler worked with a vendor to make tablets derived from milled and powdered broccoli seeds and freeze-dried broccoli sprouts. Because of the coronavirus pandemic, Kensler could not retrieve these samples yet, but his research has not stopped. He is now working on using green chemoprevention for enhancing health in space as it could soon one day protect astronauts from cosmic radiation. I chose this article because I could not imagine what was once a side dish being something key in halting cancer development. Kensler’s research is important because it showcases how nature and earth’s very own resources could potentially solve many problems related to medicine. If something so simple as broccoli could be the future of cancer prevention, imagine what other resources out there could potentially save lives.
Kensler’s most recent trial in China, his first evaluation of his supplement approach.
Photo courtesy of Dr. Tom Kensler
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