MD Anderson Research Highlights for December 18, 2024

Featuring smoking cessation treatments, radiation for metastatic thyroid cancers, pancreatic cancer insights, and biomarkers for appendix cancer and leukemias

MD Anderson News Release December 18, 2024

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.

Smoking cessation medications are safe and effective for people with depression
Individuals with major depressive disorder (MDD) are more likely to smoke, leading to higher risks of nicotine addiction and early death from tobacco-related illnesses. To identify the best treatments for quitting, researchers led by George Kypriotakis, Ph.D., and Paul Cinciripini, Ph.D., evaluated the safety and efficacy of three smoking cessation monotherapies previously approved by the Food and Drug Administration – varenicline, bupropion and nicotine patches – on 6,553 participants with current or past MDD. There were no differences in risk of neuro-psychiatric adverse events based on medication among all participants. According to the study, varenicline plus counseling had greater efficacy – continuous abstinence during the nine to 12-week period – and may be the best treatment for individuals with past or current MDD. Participants with current MDD also had reduced anxiety and depression while trying to quit. The study highlights the safety and efficacy of these medications for MDD and emphasizes the continued need for more research to address both untreated depression and nicotine addiction to improve outcomes. Learn more in The American Journal of Psychiatry.

Definitive radiotherapy demonstrates effectiveness in metastatic thyroid cancers
Definitive radiotherapy (dRT), intended for long-term disease control, is an effective option for several solid tumors that are oligometastatic, meaning they have limited metastatic lesions, or oligoprogressive, meaning few metastases are progressing. However, the benefit of dRT for metastatic thyroid cancers is largely unknown. Researchers led by Matthew Ning, M.D., examined the use of targeted dRT using stereotactic body radiotherapy (SBRT) in 119 patients with oligometastatic/oligoprogressive thyroid cancer. Treatment with dRT showed a 91% local control rate for treated sites at three years and was associated with significant delays in the need for systemic therapy, the current standard of care. Only 2.5% of patients experienced grade 3 toxicities, with no higher-grade events. The median time to systemic therapy escalation, which can bring significant adverse effects and impact quality of life, was more than four years. While further studies are needed, this study highlights the potential of dRT in controlling oligometastatic and oligoprogressive thyroid cancers. Learn more in the Journal of the National Comprehensive Cancer Network.  

Targeting signaling pathway may overcome treatment resistance in pancreatic cancer
Many patients with late-stage pancreatic cancer develop resistance to various treatments including first-line chemotherapy, highlighting a need to identify and understand the mechanisms of resistance. To provide insights, researchers led by Yohei Saito, Ph.D., Yi Xiao, Ph.D., and Dihua Yu, M.D., Ph.D., examined single-cell transcriptomic data from models of pancreatic cancer and clinical pathological information from patients with pancreatic cancer. They discovered a novel signaling circuit – Yap1 in cancer cells and Cox2 in fibroblasts of tumor microenvironment – that is activated during chemotherapy and helps these cancer cells survive. Co-targeting Yap1 in cancer cells and Cox2 in fibroblasts effectively overcame chemotherapy resistance and significantly extended survival in preclinical models. Interestingly, clinical analyses revealed that patients with pancreatic cancer who received statins, which inhibit Yap1, and aspirin, which targets Cox2, had prolonged survival during chemotherapy. These findings further highlight the therapeutic potential of co-targeting this signaling circuit to overcome resistance and improve patient outcomes. Learn more in Cell Discovery.

ctDNA in appendix cancer reveals new insights for prognosis and treatment
Appendiceal adenocarcinoma (AA), a rare type of appendix cancer, can be challenging to detect. While it is often treated with surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), better tools are needed to guide patient selection, monitoring and treatment decisions. Researchers led by Michael White, M.D., and John Paul Shen, M.D., analyzed circulating tumor DNA (ctDNA) in AA and identified a unique mutational profile, with TP53 mutations being the most common. They detected ctDNA less frequently in metastatic AA and at lower levels than in colorectal cancer, suggesting that AA sheds less DNA into the bloodstream. Detectable ctDNA was associated with lower survival rates, highlighting ctDNA’s potential as a valuable tool for identifying AA patients with poorer prognoses. This approach could enhance patient selection and monitoring in AA care. Learn more in Clinical Cancer Research.

TP53 aberrations affect treatment response and survival in myeloid leukemias
TP53 genetic alterations are associated with poor outcomes in myeloid leukemias, but their exact impact on treatment response and survival, considering newer treatment options and allogeneic hematopoietic stem cell transplantation (HSCT), warrants further evaluation. In a new retrospective study, researchers led by Jayastu Senapati, M.D., D.M., Sanam Loghavi, M.D., and Naval Daver, M.D., analyzed 413 newly diagnosed patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 mutations. They characterized the relationship between patient outcomes and multiple variables, such as age, disease state, TP53 mutation burden, and therapy received. The study found improved survival outcomes in those with AML and a low-risk TP53 aberration and all patients treated with an HSCT. The overall response rate was 62% and 53% in patients with MDS and AML, respectively. Patients with AML also had higher overall response rates and composite complete response rates when treated with venetoclax, although this did not translate to higher rates of allogeneic HSCT or survival. The comprehensive analysis highlights the importance of knowing a patient's burden of TP53 aberrations to predict outcomes and determine better therapeutic strategies. Learn more in Haematologica. 

Awards and Honors

MD Anderson at ASH 2024
Read below for highlights from MD Anderson researchers at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition. More information can be found at MDAnderson.org/ASH.

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Read below to catch up on recent MD Anderson press releases.