HOUSTON – The University of Texas MD Anderson Cancer Center's Research Highlights gives a glimpse at recently published studies in clinical, translational, and basic cancer research by MD Anderson experts. The current advances include the expanded use of targeted therapy for patients with leukemia, molecular research yielding novel targets for cancer therapy, insight into radiation resistance, and a community intervention to lower cervical cancer rates.Acalabrutinib is an initial treatment for chronic lymphocyticleukemia.CLL is a form of cancer that affects the blood, bone, liver, lymph nodes and spleen. CLL is the most common form of leukemia among adults. There are many treatments available to manage and control the disease. However, it can be difficult to cure. William Wierda M.D., Ph.D. led a clinical trial that showed that acalabrutinib can be safely and effectively used to treat CLL. This drug selectively inhibits Bruton’s tyrosine kinase. Although the drug has been used previously for CLL relapses, this trial shows that it can be safely and effectively used in patients who have not received chemotherapy or any other treatment. 97% of the 99 patients who were treated responded to the treatment. After 53 months, 85 patients continued treatment. 38 percent of patients suffered side effects such as hypertension, infection, and atrial fibrillation. Acalabrutinib was shown to be safe and durable in the trial. It can therefore be considered an option for patients with CLL who are symptomatic. Read more at Blood.A novel treatment for cancer may include a DNA-cutting enzymeThe interface between old and new DNA is created during DNA replication. This structure is known as the replicationfork. Stalls at this fork can cause replication stress and genetic instability, which is a hallmark sign of cancer. John Tainer, Ph.D. and Chi-Lin Tsai at MD Anderson found that exonuclease 5 (EXO5) plays a crucial role in restarting stalled replicating forks. Researchers solved the structure of EXO5 and bound it to DNA. This knowledge is crucial for structural-based drug discovery. Their research suggests that EXO5, which has a high incidence in tumors associated with poor patient survival rates, could be used as a novel treatment strategy. Read more at Molecular Cell.Cancer cells reprogram the Golgi apparatus in order to increase pro-tumor proteins secretionCancer cells secrete more pro-tumor signaling protein than normal. This can cause the microenvironment to reorganize and promote tumor growth, metastasis, and therapeutic resistance. Jonathan Kurie's lab has released two new studies that reveal how genetic changes in cancer can lead to hypersecretion of the Golgi apparatus. These findings may help to develop therapeutic strategies to stop these pathways. Xiaochao Tan's Ph.D. research published in Science Advances found that TP53 loss reprograms Golgi proteins to promote the secretion pro-metastatic protein. These Golgi proteins were blocked, which resulted in metastasis and growth of cancers with p53 deficiency. It also inhibited immune suppression within the tumor microenvironment. Lei Shi, Ph.D. published a study in Proceedings of the National Academy of Sciences. It found that lung cancers affected by chromosomal abnormalities become dependent on synthesis of the PI4P lipid – part of the Golgi cell membrane - to increase secretion and ensure cancer cell survival. In genetically-defined lung carcinomas, this dependence on a particular lipid may be a weakness to target.Resistance to radiation therapy is a previously undiscovered role for proteinRadiation therapy is one pillar of cancer treatment. It's used to cause DNA damage and eventually cell death in cancer cells. Normal cells can repair much of the damage, while cancer cells are often unable to. Some cancers are resistant to radiation therapy, which makes it less effective. Qinglei Hang and Li Ma, Ph.D. discovered that DGCR8 is involved in the generation of small RNA molecules known as microRNAs. After ionizing radiation is applied, DGCR8 can be modified and stabilized. This allows other proteins to join together and repair DNA damage caused by cancer cells. These results suggest that targeting DGCR8 and its partners could be a way to make tumors more sensitive to radiation and overcome resistance to therapy. Read more at Nature Communications.Neoadjuvant immunotherapy for resectable neck and head cancerSurgery followed by radiation therapy is the standard of care for locoregionally advanced, resectable cutaneous squamous cells carcinoma of head and neck (CSCCHN). Patients who receive this aggressive treatment can experience disfigurement and functional loss. About 30% of them will also experience disease recurrence. Neil Gross, M.D. led a Phase II clinical trial in which 20 patients with resectable Stage III-IVA CSCC–HN were treated with two cycles of the PD-1 inhibitor Cemiplimab. Cemiplimab can be used to treat unresectable CSCC–HN. However, this study is the first to examine neoadjuvant treatment for resectable CSCC–HN. Cemiplimab is safe and effective with a 70% pathologic response rate. Many patients were able to avoid radiation therapy and remain cancer-free for nearly two years. An inflamed tumor microenvironment and enrichment of CD8+ cells was responsible for the response. Read more in Clinical Cancer Research, the journal of American Association for Cancer Research.New treatment targets for KRAS-mutant pancreatic carcinomaThe United States' leading cause of death from cancer is still pancreatic cancer. Over 90% of pancreatic cancer cases are due to mutations in KRAS. However, there are no targeted therapies available to treat the most common KRAS mutations. To identify new targets downstream from KRAS signaling, a research team consisting of Liang Yan, Wantong Yao M.D., Ph.D. and Haoqiang Yang Ying, Ph.D. was led by Haoqiang Yan, Ph.D. The RAF/MAPK signaling pathway was confirmed as a crucial downstream component. However, blocking this pathway with MEK inhibitors only proved ineffective. The model also showed significant reprogramming in cellular metabolism downstream mutant KRAS. Pancreatic cancer cells were sensitive to MEK inhibitor treatment for glucose metabolism. This combination showed strong anti-tumor effects, suggesting that further research is warranted. The American Association for Cancer Research publishes Cancer Research as a journal.Community program to combat high rates of cervical cancer in Rio Grande ValleyThere are significant cervical cancer disparities along the Rio Grande Valley border between Texas and Mexico. In this area, the incidence and mortality rates for cervical cancer are about 55% higher than the U.S. average. Preventing cervical cancer can be done with HPV vaccination, early diagnosis and treatment for precancerous cervical dysplasia. Kathleen Schmeler, M.D. led a community-based team to increase cervical cancer screening, diagnosis, and treatment. Over four years, the program provided cervical cancer screening for 14,846 women. Over the four-year period, 2,030 women had colposcopy for abnormal findings (179% more than baseline) and 453 were treated with cervical dysplasia. The procedures were performed by local providers who received bi-weekly continuing education via virtual mentoring through Project ECHO. View more at Perspectives in Public Health.###If you haven't seen it, here it isYou can find the most recent MD Anderson press releases from across all areas of cancer research by clicking here.* Engineered NK cell can eradicate glioblastoma stems cellsAbout MD AndersonHouston's University of Texas MD Anderson Cancer Center is a top-ranked center that focuses on patient care, research and prevention. The institution has one mission: to eradicate cancer from patients and their families all over the globe. MD Anderson is one 51 comprehensive cancer centers that have been designated by the National Cancer Institute (NCI). U.S. News & World Report's survey of the "Best Hospitals", ranked MD Anderson as No.1 in cancer care. Since 1990, MD Anderson has been ranked among the top two hospitals in the country for cancer care. It also ranked first 15 times over the past 18 years. MD Anderson is awarded a Cancer Center Support Grant from the National Institutes of Health (P30CA016672).2021 University of Texas MD Anderson Cancer Center
