MD Anderson Research Highlights for March 8, 2023
Long noncoding RNA targets for breast and pancreatic cancer, a new marker to identify metastatic gynecologic cancers, and a new target to overcome drug resistance in AML
MD Anderson News Release March 08, 2023
The University of Texas MD Anderson Cancer Center’s Research Highlights showcases the latest breakthroughs in cancer care, research and prevention. These advances are made possible through seamless collaboration between MD Anderson’s world-leading clinicians and scientists, bringing discoveries from the lab to the clinic and back.
Recent developments include overlooked proteins from long noncoding RNAs that likely play a functional role in breast cancer, inhibiting tumor-associated neuronal cells to improve treatment response in pancreatic cancer, a novel and highly specific marker to identify metastatic tumors of gynecological origin, and a potential target to overcome treatment resistance in acute myeloid leukemia.
“Hidden” proteins from long noncoding RNAs might play functional role in cancer
The GENCODE project showed that roughly 70% of the human genome is transcribed into RNA, including many long noncoding RNAs (lncRNAs), defined as RNA molecules longer than 200 nucleotides that lack protein-coding potential. However, recent evidence suggests some lncRNAs may produce “hidden” proteins whose potential role in cancer remains unknown. To investigate this, researchers led by Yiwen Chen, Ph.D., used an integrative genomic strategy combining CRISPR/Cas9 knockout screens with data from The Cancer Genome Atlas. The researchers uncovered lncRNA-encoded proteins that might be involved in estrogen receptor α-positive luminal breast cancer, the most common breast cancer subtype. They confirmed the in vivo tumor-promoting function of a hidden protein encoded by a lncRNA whose expression is associated with poor prognosis. These findings suggest that the hidden lncRNA-encoded proteins should be further studied for potential therapeutic targets. Learn more in The Journal of Clinical Investigation.
Inhibiting specific neuronal cells improves responses in pancreatic cancer in vivo
Pancreatic cancer is notoriously difficult to treat, partly due to a tumor microenvironment that is highly resistant to immunotherapy. Data for nonmyelinating Schwann cells, which wrap around small neuronal axons to provide support and to promote new sprouting, suggests these cells may facilitate pancreatic tumor invasion into the nervous system. To further understand the role of these cells, researchers led by Liuqing Yang, Ph.D., and Chunru Lin, Ph.D., characterized the gene signature of tumor-associated nonmyelinating Schwann cells (TASc). The researchers found that the abundance of TASc was correlated with poor patient outcomes. More specifically, TASc express a long noncoding RNA (lncRNA) named PVT1, which triggers a signal pathway that promotes tumor growth. Using a TASc inhibitor in vivo improved treatment response to immune checkpoint inhibitors, highlighting TASc and lncRNAs as potential therapeutic targets for pancreatic cancer. Learn more in Science Advances.
Study finds novel biomarker for ovarian and endometrial origins of metastatic cancer
To determine the appropriate treatment approach for metastatic cancer, it is critical to identify a tumor’s primary site of origin. Specific biomarkers to assist with proper diagnosis could benefit clinicians and patients. PAX8 is commonly used to determine if a tumor is of gynecologic origin, but it also is highly expressed in other cancers such as thyroid and renal carcinomas, making it difficult to reliably diagnose tumors with ovarian and endometrial origin. To identify a more specific biomarker, researchers led by Jinsong Liu, M.D., Ph.D., and Qingqing Ding, M.D., Ph.D., mined mRNA expression profile data from The Cancer Genome Atlas and performed immunological staining in a large cohort of ovarian and endometrial cancer along with samples from other cancer types. They found SOX17 was highly expressed in different subtypes of ovarian and endometrial carcinomas but was not expressed in thyroid or renal carcinomas. In addition, SOX17 is not expressed in peritoneal mesothelioma and breast cancer, whose tumors often are confused with ovarian cancer. The data suggest SOX17 represents a sensitive and specific marker for identifying tumors of gynecological origin. Learn more in Modern Pathology.
Targeting ULK1 overcomes adaptive drug resistance in acute myeloid leukemia
Adaptive resistance in leukemic stem cells (LSCs) remains an obstacle in successfully treating acute myeloid leukemia (AML). Previous research found LSCs are addicted to autophagy induction as a key mechanism for adaptive resistance, helping cells maintain stability and survive under stress. At diagnosis, LSCs express higher levels of the enzyme ULK1, which initiates autophagy, compared to normal cells. ULK1 also is upregulated when exposed to chemotherapy and targeted agents, making it a potential therapeutic target. Researchers led by Gautam Borthakur, M.D., demonstrated that targeting ULK1 in lab models suppresses treatment-induced autophagy, overcomes adaptive drug resistance, and improves response to chemotherapy and emerging anti-leukemia agents. The data support further investigation of ULK1 as a candidate target for combination therapies in clinical trials of AML. Learn more in Molecular Cancer Research.
Recent awards and honors
- The University of Texas MD Anderson Cancer Center was awarded the DeWitt C. Baldwin, Jr. Award, presented by the Accreditation Council for Graduate Medical Education and the Arnold P. Gold Foundation
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