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Scientist Honored for Discovering a Weakness in Aggressive Lung Cancer

image of small cell lung cancer tumor
Ion beam image of small cell lung cancer tumor and its microenvironment of immune cells. | Y. Xie, Y. Li, and T. J. Hollmann/MSKCC

Triparna Sen has been awarded the 2021 AAAS Martin and Rose Wachtel Cancer Research Award for her pioneering work in potential new treatment strategies for small cell lung cancer, an aggressive and deadly lung cancer that often resists chemotherapy.

Throughout her studies, Sen has studied the link between the formation of tumors and the replication stress response, a molecular pathway that allows cancer cells to survive the stresses of replicating DNA and cell division. Her experiments in cells and mice show that molecules that inhibit this response can sensitize small cell lung cancer to immunotherapy.

Sen, assistant attending at Memorial Sloan Kettering Cancer Center in New York City, discussed her prize-winning research at a presentation on August 6 during a virtual ceremony hosted by the U.S. National Institutes of Health. She also wrote an essay on her work that was published in the August 4 issue of Science Translational Medicine.

"[Dr. Sen] is recognized for identifying that the replication stress response in small cell lung cancer can be exploited therapeutically to boost the antitumor immune response," said Orla Smith, editor of Science Translational Medicine.

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

"With all the challenges that I run across in the world, and I know that there are times when it can feel overwhelming, I derive hope and optimism when I interact with early-career researchers who I know are going to lead us to the next era of research, treatments, and dare I say it, cures," said Sudip Parikh, chief executive officer of AAAS.

As part of the award, Sen will receive a plaque and a check for $25,000 dollars, funded by an endowment bequeathed by Martin L. Wachtel.

"This award highlights the work of early-career investigators," said Tom Misteli, director of the Center for Cancer Research at the National Institutes of Health. "We recognize they really are the future of all our institutions, and they will shape how we do science and the kinds of science we do in the future."

Although Misteli noted early-career investigators and trainees have been hit particularly hard by disruptions from the pandemic, he stressed that "we see [them] continue to do what they usually do, which is doing great science and making important contributions to research."

"So in that spirit, the Wachtel award this year highlights the outstanding science done by an early career investigator … but also acknowledges the challenges they are facing, especially at the moment," he added.

An Urgent Need for New Treatments

Lung cancer causes the most deaths from cancer in both men and women, making it a top priority for researchers and health agencies. Small cell lung cancer is a particularly aggressive form of lung cancer that makes up around 10% to 15% of all cases of lung cancer, according to the American Cancer Society.

Triparna Sen

Approximately 30,000 Americans die from small cell lung cancer each year, and more than 200,000 people perish from the cancer worldwide annually, according to Sen's essay. Patients with advanced cases of the cancer face dismal survival rates, which can fall below 5% after two years.

Small cell lung cancer is so deadly because tumors are usually highly invasive. Furthermore, cancer cells frequently start resisting chemotherapies after the first rounds of treatment, leaving patients and clinicians with few options.

These challenges prompted the National Cancer Institute to make small cell lung cancer one of the two cancer types focused on in the Recalcitrant Cancer Research Act of 2012, which supports research frameworks and funding for cancers with poor survival rates.

"Given the critical need for scientific and treatment advancement, I wanted to study this disease," Sen said. "I wanted to improve the biological understanding and identify effective therapies for small cell lung cancer."

Uncovering a Weak Spot in Small Cell Lung Cancer

Sen and her colleagues have focused on defining the proteins, enzymes, and other factors that coordinate the replication stress response in cancer cells. Recently, her team discovered that inhibiting some of these proteins can sensitize small cell lung cancer tumors in mice to other treatments.

For example, Sen discovered that inhibiting the enzyme CHK1 with the experimental molecule prexasertib sensitized small cell lung cancer to the effects of immune checkpoint blockade treatment, which usually doesn't work against small cell lung cancer. Her group's study was the first to show that inhibiting the replication stress response could sensitize small cell lung cancer to immunotherapy, she said.

"We anticipate that our work will have a large impact on reducing morbidity and improving the quality of life of patients with small cell lung cancer or other malignancies harboring [replication stress response] defects," Sen writes.

Sen plans to further study how the different subtypes of small cell lung cancer differ in their effects on the immune system. She's also planning to investigate how these tumors might become resistant to chemotherapies and inhibitors of the replication stress response, as well as define strategies to "reactivate" the immune system against small cell lung cancer.

Her team is also applying advanced single-cell sequencing — a precise form of genetic analysis — to capture patterns in the activity of genes in both tumor cells and immune cells in samples from patients.

"I am really excited about this as this provides us the opportunity to study small cell lung cancer in unprecedented resolution and will surely advance [our] scientific knowledge," Sen said.