It was the mid-'80s and the height of the federal government's war on drugs. Hadiyah-Nicole Green's St. Louis neighborhood was full of kids struggling with addiction. But her aunt, Ora Lee Smith—who adopted Green when she was four—prided herself on making "a way out of no way." She and her husband General Lee raised their adoptive daughter on a philosophy of determination. By the time Green graduated from Alabama A&M University with a 4.0 in physics, she had a full scholarship to grad school for biomedical engineering. Then, the day after graduation, her aunt made an announcement that would change the course of Green's life: She had what she called "woman's cancer," and she was refusing treatment because of the side effects. (The family still doesn't know Ora Lee's exact diagnosis, but it was likely ovarian or cervical cancer.) That summer, Green watched Ora Lee deteriorate. She marveled at how little the doctors could do for her aunt without using aggressive therapies that threatened to be even more painful than what she was already experiencing. Three months after Ora Lee died, her husband was diagnosed with esophageal cancer. Unlike his wife, he opted for chemotherapy and Green moved back to St. Louis from graduate school at UC Davis to see him through it. She watched as he lost two hundred pounds, all the hair on his head, his eyelashes, and his eyebrows. His fingernails turned black and his skin "looked like it'd been barbecued. It was horrible. Just horrible," Green recalls. It's one of the few moments when her typical effervescence fades. "When I was taking care of my aunt, I was like, There must be something better than just dying like this," Green, now a medical physicist, says. "Then, watching my uncle go through chemo and radiation, I was like, This isn't that much better; it's maybe even worse."
Green didn't have any formal experience studying cancer, but she'd taken a particular interest in lasers and optics when she interned at NASA. "I was like, Okay, we're able to see from outer space if a dime on the ground is face up or face down, and we can cause a particular cell phone to ring in a room, but we have to treat the whole person in order to treat a tumor. This seems backwards to me," she says. She sketched out an idea in her notebook: a liquid solution made of tiny particles that could be injected directly into a solid tumor. A laser light would then be shot at this solution, heating it up, and killing the cancer cells. Unlike chemotherapy or radiation, the treatment would be local, leaving healthy cells in the body completely untouched and, thus, sparing the patient any side effects. Now, nearly 15 years later, Green's treatment has materialized—and expanded to include a 2.0 version that treats cancers that are not just confined to one part of the body. "There is a better way to treat cancer," she says about the current state of oncology. It's a bold statement for a 36-year-old who completed her PhD just five years ago. She's young for her field, doe eyes and a playful manner making her seem even younger. She describes her treatments with the enthusiasm and simplicity of a science teacher who adores her students.
The 1.0 version of Green's treatment is called laser-activated nanotherapy (LANT). It continues to be a local treatment as she initially envisioned, with that laser light that heats up nanoparticles that have been injected directly into a solid tumor, killing the cancer cells. One ten-minute LANT treatment in mice has led to a nearly 100 percent reduction in the size of solid tumors, found a study published in the International Journal of Nanomedicine. "You can literally see the tumor disappear over the course of 15 days," Green says. LANT is ready to be tested in humans, but Green needs to raise an additional $9 million before she can start enrolling volunteers.
Green's 2.0 version—developed for metastatic cancers that are not confined to one part of the body—combines the laser-activated nanotherapy with drugs called antibodies. These antibodies, which are already FDA-approved and of which there are many different kinds depending on the type of cancer being treated, circulate through the body like a GPS system, find the cancer cells, attach to them, and then destroy them. It can be an effective way to target cancer tumors and lesions that physicians can't locate.
Antibodies are typically used as a part of a promising cancer treatment called immunotherapy, which stimulates the body's immune system to fight cancer. But instead of waiting for the antibodies to destroy the cancer cells, Green's 2.0 treatment—called FLALANT, for fluorescently-labeled bodies and laser-activated nanotherapy—uses the antibodies' ability to find tumors and lesions throughout the body as a delivery vehicle for her nanoparticles. Green technique added a unique feature to the antibodies—a bright green dye—that allows a doctor to use imaging technology to see the site of the cancer cells lit up once the antibodies have attached to them. Then, the physician can target the tumors and lesions, just like in Green's 1.0 version, with the laser light which heats up the nanoparticles inside the antibodies and kills the cancer cells.
Green has received a $1.1 million research grant from the Department of Veterans Affairs in order to further develop FLALANT before testing it in humans. She has yet to publish her results, but in mice, it led to a 40 percent reduction in tumor size over two days, something that typically takes months with immunotherapy alone.
The treatment seems promising, says Mario Curti, a medical oncologist at Los Alamitos Medical Center in Los Alamitos, California, who is unaffiliated with Green but familiar with the concepts behind her work. This kind of treatment—which targets the cancer cells without side effects—has historically been considered the "holy grail" in oncology. But, he points out, there've been attempts over the decades to do something similar, and it's going to be challenging to raise the money to get it to market. "I applaud her," Curti says. "The reality is she's going to have an uphill climb." Green knows this, and she's undeterred. She says the field of cancer is long overdue for something groundbreaking after "billions of dollars in taxpayer money and 40 years has only led to incremental progress." Besides, she's accustomed to challenge. She's the first one in her family to go to college. She's one of only 66 black women in the United States to receive a PhD in physics between 1973 and 2012. And shortly after receiving her doctorate, she was hired as assistant professor at Tuskegee University and given her own lab—something scientists generally only receive after years of doing postdoctoral research for someone else. Last year, Green made another nontraditional decision when she founded a nonprofit in her aunt's name to raise money for her trials. This move is intended to keep the price of her treatment affordable, particularly for African Americans who continue to die from most cancers at higher rates than their white counterparts. It means, however, that she has to raise an estimated $130 million in individual donations if she wants to get both treatments through the necessary FDA-clinical trials for market.
Green grew up, she says, acutely aware of the difference between the "haves" and the "have nots." General Lee drove trucks for Coca Cola. Ora Lee used to take Green with her when she cleaned the home of the local Catholic minister. She vividly recalls Ora Lee once instructing her to help with the cleaning in case she ever needed a similar job for extra money. The young Green scoffed at the idea and refused. Green wonders now if her aunt and uncle might have gotten better medical treatment under different circumstances. Ora Lee wasn't diagnosed until her cancer was advanced, and, when she was, she was uncomfortable speaking with anyone about what she was going through. This is a common problem in the African American community, in which patients are often diagnosed later, don't have access to proper care, and opt out of treatment because they don't trust their physicians, says Marvella Ford, associate director of Cancer Disparities at MUSC's Hollings Cancer Center. There's also the simple problem of cost. General Lee was diagnosed earlier than Ora Lee, but he didn't have extensive treatment options on Medicaid.
A major aim of Green's second treatment for metastatic cancers is to reduce the amount of time a person is on immunotherapy, thus reducing the side effects and cost. While immunotherapy is significantly less invasive than chemotherapy or radiation, it can overstimulate a patient's immune system, leading to arthritis and colitis (an inflammatory bowel disease), among other serious conditions. Additionally, on a typical immunotherapy treatment plan, one injection costs between $5,000 and $10,000, and they can be needed as often as every two to three weeks for the rest of a patient's life. Despite programs that help people get these treatments affordably, they can be challenging to navigate. Green says she's "extremely" confident her treatments will work in humans, but she knows she won't gain significant traction in her field until she publishes more papers. Warren Chow, longtime clinical professor at City of Hope Medical Oncology, affirms this. "An idea can sound good," he says, "But the problem is everything's kind of BS until it's been peer-reviewed." He also says, regarding her 2.0 treatment, that the field of oncology has recently "tempered their enthusiasm" about immunotherapy as it only increases long-term survivability for 15 to 20 percent of cancers (a stat some physicians nonetheless still find transformative). Green is used to encountering this sort of doubt, particularly from cancer researchers and physicians who have seen treatment ideas come and go for decades. Her colleague James Lillard, associate dean of research at Morehouse School of Medicine, anticipates she'll come up against the bias in oncology toward researchers who seem too young, and ideas that seem too innovative. But, he says, he has faith that ultimately her "data will speak for itself." Lillard has followed Green's treatment since she was first developing it as a student, and then later helped recruit her to Morehouse. He calls her a "strong, well-trained scientist" who is "refreshingly enthusiastic." Any resistance she encounters, he says, will likely only serve as her fuel.
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