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Scientist Receives Award for Decrypting Treatment Resistance in Cancer

color image of metastatic melanoma cells
Obenauf's research looks at how metastatic melanoma cells such as these evade treatment. | Julio C. Valencia, NCI Center for Cancer Research

The 2022 AAAS Martin and Rose Wachtel Cancer Research Award has been awarded to cancer researcher Anna Obenauf, whose work has decrypted how cancer cells gain the ability to resist common cancer drugs and immunotherapies.

Throughout her career, Obenauf has made strides in understanding the evolution of treatment resistance in cancer cells, which is one of the largest causes of death in patients with late-stage metastatic cancers. By better defining these events, her research could lead to more effective combination therapies for metastatic cancer.

"With this arsenal of therapies, cancer research is entering an exciting era in which individual therapies serve as building blocks for combinations to accomplish what monotherapies often cannot: durable tumor control in the majority of patients with metastatic cancer," Obenauf writes in her prize-winning essay published in the July 27 issue of Science Translational Medicine.

Obenauf, group leader at the Research Institute of Molecular Pathology in Vienna, Austria, also presented on her award-winning work during a July 29 virtual ceremony hosted by the U.S. National Institutes of Health.

"Dr. Anna Obenauf was selected as the winner of this year's award based on her outstanding work uncovering molecular determinants of response and resistance to targeted therapies and immunotherapies," said Dorothy Hallberg, an associate editor at Science Translational Medicine.

"Dr. Obenauf and her lab's work on mechanism-based combination therapies for metastatic cancer has the possibility to improve outcomes for many patients with late-stage disease," she added.

The AAAS Martin and Rose Wachtel Cancer Research Award is a yearly prize that highlights early-career scientists who have made outstanding contributions to the field of cancer research.

Anna Obenauf

Obenauf will receive an award plaque and a check for $25,000, funded by an endowment bequeathed by Martin L. Wachtel.

"Martin Wachtel was a very practical and entrepreneurial man, and a businessman," said Tom Misteli, director of the Center for Cancer Research at the National Institutes of Health, when discussing the award's primary benefactor.

"But he also understood something that's very important about science and research," Misteli noted. "And that is that one of the most impactful ways to promote research and science is to support new and early investigators, which is what the Wachtel award does."

CaTCHing onto the Roots of Treatment Resistance

Although chemotherapy and surgical treatments can have initially positive results, some patients eventually rebound and relapse. This usually happens when the surviving tumor cells regrow and eventually stop responding to standard cancer drugs.

Treatment resistance is especially problematic in the case of metastatic cancer , or cancers where the primary tumor has spread to distant areas in the body. Patients who relapse have few remaining treatment options, so survival rates remain dismally low for metastatic tumors.

From her early days as an undergraduate, Obenauf said she has been fascinated by how tumors end up becoming resistant to immunotherapy and other newer cancer therapies.

One key event for her was an American Association for Cancer Research meeting, which she attended during her first year as a postdoctoral fellow. There, Obenauf learned of researchers' attempts to treat melanoma with targeted therapy — a type of cancer treatment that targets specific proteins associated with tumors.

"It was already clear that resistance would be a major hurdle in achieving long-term tumor control, and so many fundamental questions remained unanswered," she said. "I knew then that I wanted our research to help solve some of these mysteries."

Since then, Obenauf has focused on understanding why and how the tumor and its surrounding environment respond to targeted therapies and immunotherapies, and how these responses lead to treatment resistance during metastasis.

One of her lab's major accomplishments has been the creation of CaTCH, a research tool that she likened to a "time machine" for cancer cell evolution. In a nutshell, CaTCH places fluorescent barcodes of DNA onto tumor cells, allowing researchers to precisely map the evolution of millions of cancer cells as they acquire new mutations.

CaTCH is now being used by researchers around the world in both basic and translational research to understand how various types of cancer cells develop during metastasis and the onset of treatment resistance, according to Obenauf.

By defining these drivers of treatment resistance, her team's discoveries could help scientists design more effective combination therapies that can kill cancers, while minimizing the risk of treatment resistance or even cross-resistance across therapies.

For example, her work implies that the order in which immunotherapy and targeted therapy are given can have a major impact on treatment responses — a discovery that she said could have immediate implications for treating malignancies such as melanoma.

"Our work contributed to highlighting that the sequence [of] how drugs are administered can be crucial for therapy response, even if it involves therapies with a completely different mode of action," Obenauf said.

When asked about her future plans, Obenauf said her group is keen to test new types of combination therapies. These combos could include clinically used immunotherapies and targeted therapies as well as more experimental strategies based on their discoveries.

Her lab also plans to expand their studies to cancers beyond melanoma, including certain subtypes of lung cancer and colorectal cancer. They also have several ongoing projects with some rare types of skin cancers and are studying how these cells can generally evade the immune system.