Rice biochemist Natasha Kirienko and MD Anderson physician-scientist Marina Konopleva made the striking discovery. Photo by Jeff Fitlow

Rice University and MD Anderson researchers have just discovered a potential one-two punch that could, they hope, knock out an insidious disease.

A recent study in the journal Leukemia centers on potential new drugs that, with the help of other medications, can thwart leukemia cells.

Specifically, Rice biochemist Natasha Kirienko and MD Anderson physician-scientist Marina Konopleva screened some 45,000 small-molecule compounds to find a few that targeted mitochondria, according to Rice press materials.

In this innovative new study, the team selected eight of the most promising compounds, identified between five and 30 closely related analogs for each, and conducted tens of thousands of tests to systematically determine how toxic each analog was to leukemia cells. This was measured both when administered individually or in combination with existing chemotherapy drugs like doxorubicin, notes a release.

Previously, Kirienko’s lab had shown the eight compounds targeted energy-producing machinery inside cells called mitochondria. Mitochondria, which work nonstop in every living cell, wear out with use. The chosen eight compounds induce mitophagy, which can be described as how cells decommission and recycle deficient and used-up.

Notably, during times of extreme stress, cells can temporarily forgo mitophagy for an emergency energy boost. Previous research has shown leukemia cells have far more damaged mitochondria than healthy cells and are also more sensitive to mitochondrial damage than healthy cells.

Thus, Kirienko and Konopleva reasoned that mitophagy-inducing drugs might weaken leukemia cells and make them more susceptible to chemotherapy. Synergy — using two or more drugs in treatment — is key.

“The point of synergy is that there are concentrations, or dosages, where a single drug doesn't kill,” Kirienko said. “There is no death of healthy cells or cancer cells. But administering those same concentrations in combination can kill a considerable amount of cancer cells and still not affect healthy cells.”

The team tested the toxicity of its mitophagy-inducing compounds and combinations against acute myeloid leukemia (AML) cells, the most commonly diagnosed form of the disease. They then tested the six most effective AML-killing compounds against other forms of leukemia, finding that five were also effective at killing acute lymphoblastic leukemia (ALL) cells and chronic myelogenous leukemia (CML) cells.

Studies found all the mitophagy-inducing drugs caused far less harm to healthy cells.

Finally, the researchers tested one of the most effective mitochondria-targeting compounds, PS127E, using a cutting-edge technique called a patient-derived xenograft (PDX) model. Also referred to as a “mouse clinical trial,” mice are implanted with cancer cells from a leukemia patient. As the cells grow, the mouse is exposed to a drug or combination of drugs as a closer-than-cells test of the treatment’s effect.

Importantly, PDX tests on one compound, PS127E, showed it was effective at killing AML cells in mice, Rice notes, signaling promising news.

“Although this is very promising, we’re still some distance from having a new treatment we can use in the clinic,” Kirienko added. “We still have a lot to discover. For example, we need to better understand how the drugs work in cells. We need to refine the dose we think would be best, and perhaps most importantly, we need to test on a wide variety of AML cancers. AML has a lot of variations, and we need to know which patients are most likely to benefit from this treatment and which are not. Only after we’ve done that work, which may take a few years, would we be able to start testing in humans.”

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This article originally ran on CultureMap.

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Mark Cuban calls AI ‘the greater democratizer’ for young entrepreneurs

eyes on AI

Texas billionaire Mark Cuban—whose investment portfolio includes Houston-based Holliball, a startup that makes and sells large inflatable holiday ornaments—believes AI is leveling the playing field for budding low-income entrepreneurs.

At the recent Clover x Shark Tank Summit in Las Vegas, the Shark Tank alum called AI “the greater democratizer.”

Cuban told Axios that free and low-cost AI tools enable disadvantaged teenagers to compete with seasoned professionals.

“Right now, if you’re a 14- to 18-year-old and you’re in not-so-good circumstances, you have access to the best professors and the best consultants,” Cuban said. “It allows people who otherwise would not have access to any resources to have access to the best resources in real time. You can compete with anybody.”

While Cuban believes AI is “the great democratizer” for low-income young people, low-income workers still face hurdles in navigating the AI landscape, according to Public Works Partners, an urban planning and consulting firm. The firm says access to AI among low-income workers may be limited due to cost, insufficient digital literacy and infrastructure gaps.

“Without adequate resources and training, these workers may struggle to adapt to AI-driven workplaces or access the educational opportunities necessary to acquire new skills,” Public Works Partners said.

Texas 2036, a public policy organization focused on the state’s future, reported in January AI jobs in Texas are projected to grow 27 percent over the next decade. The number 2036 refers to the year when Texas will celebrate its bicentennial.

As for the current state of AI, Cuban said he doesn’t think the economy is witnessing an AI bubble comparable to the dot-com bubble, which lasted from 1998 to 2000.

“The difference is, the improvement in technology basically slowed to a trickle,” Cuban said of the dot-com era. “We’re nowhere near the improvement in technology slowing to a trickle in AI.”

CPRIT hires MD Anderson official as chief cancer prevention officer

new hire

The Austin-based Cancer Prevention and Research Institute of Texas, which provides funding for cancer research across the state, has hired Ruth Rechis as its chief prevention officer. She comes to CPRIT from Houston’s University of Texas MD Anderson Cancer Center, where she led the Cancer Prevention and Control Platform.

Before joining MD Anderson, Rechis was a member of the executive leadership team at the Livestrong Foundation, an Austin-based nonprofit that supports people affected by cancer.

“Ruth has widespread connections throughout the cancer prevention community, both in Texas and across the nation,” CPRIT CEO Kristen Doyle said in a news release. “She is a long-term passionate supporter of CPRIT, and she is very familiar with our process, programs, and commitment to transparency. Ruth is a terrific addition to the team here at CPRIT.”

Rechis said that by collaborating with researchers, policymakers, public health leaders and community partners, CPRIT “can continue to drive forward proven prevention strategies that improve health outcomes, lower long-term costs, and create healthier futures for all.”

At MD Anderson, Rechis and her team worked with more than 100 organizations in Texas to bolster cancer prevention initiatives at clinics and community-based organizations.

Rechis is a longtime survivor of Hodgkin lymphoma, a type of cancer that affects the lymph nodes, which are part of a person’s immune system.