Study identifies biomarkers for predicting treatment response in metastatic breast cancer
Standard treatment for patients with hormone receptor (HR)-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) includes cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, but nearly one-third of patients develop resistance, underscoring the need for biomarkers to predict clinical outcomes. Using single-cell RNA sequencing, researchers led by Linjie Luo, M.D., Ph.D., and Khandan Keyomarsi, Ph.D., uncovered a predictive biomarker panel for response to CDK4/6 inhibitors in HR+/HER2- mBC. Patients with higher CD8+ T cell and natural killer (NK) cell infiltration at baseline experienced longer progression-free survival, while those with late progression showed increased immune suppression, suggesting a role for immune evasion in treatment resistance. These findings challenge traditional views of CDK4/6 inhibitor resistance and suggest that CDK4/6 inhibitors could be enhanced by immune checkpoint inhibitors. With validation in two independent cohorts, these findings pave the way for precision oncology approaches to optimize treatment selection and improve patient outcomes. Learn more in Molecular Cancer.
Preclinical models uncover novel target for tumor progression in pancreatic cancer
Pancreatic cancer is notoriously difficult to treat, partly due to its tumor microenvironment, which is composed of both immunosuppressive signals and inflammatory signals that are regulated by immune cells known as tumor-associated macrophages. A subset of these macrophages has high expression of the TREM2 protein, which is involved in immune responses. Therefore, Yang Chen, Ph.D., and colleagues explored the functional role of TREM2 in pancreatic cancer progression. Using preclinical models, the researchers unexpectedly found that depletion of TREM2 in pancreatic cancer actually leads to increased inflammation and faster tumor progression. Further analysis uncovered TREM2’s role as a key braking mechanism for a pathway that results in enrichment of IL-1β+ macrophages, a different type of macrophage that promotes inflammation and tumor progression. Interestingly, inhibiting the IL-1β pathway reversed the progression caused by TREM2 depletion, highlighting a potential therapeutic strategy for this patient population. Learn more in Gastroenterology.
Abnormal chromosome changes predict survival in patients with secondary AML
Clinical secondary acute myeloid leukemia (AML) refers to patients diagnosed with AML after a prior diagnosis of myelodysplastic syndrome (MDS) or similar disorders. Conversely, patients with genomic secondary (GS)-AML have MDS-related chromosomal abnormalities and/or genetic mutations related to AML without a history of prior blood disorders or certain treatments. Researchers led by Jayastu Senapati, M.B.B.S., M.D., D.M., and Courtney DiNardo, M.D., investigated the prognostic value of different types of secondary AML – either clinical or GS –based on the disease’s origin, genetic characteristics and type of treatment. Overall outcomes across secondary AML were similar, and both were inferior to outcomes for de novo AML without any history of prior MDS. Patients with GS-AML harboring only MDS type mutations had outcomes similar to patients with de novo AML. Researchers concluded that abnormal chromosomal changes were the strongest predictor of survival in patients with secondary AML treated with venetoclax-based therapy, providing insights into how different factors affect patient outcomes. Learn more in the American Journal of Hematology.
Study provides insights into role of noncoding DNA mutations in cancer development
Many parts of noncoding DNA are highly conserved across different species, meaning they show little to no variation, and studies suggest these elements may have functional roles. Researchers led by George Calin, M.D., Ph.D., and Han Liang, Ph.D., characterized mutations in these ultraconserved elements (UCEs) to examine their potential role in cancer development. The researchers analyzed 13,736 UCEs across 2,449 primary cancer genomes, characterized their functions both in vitro and in vivo, and explored their potential clinical applications. The researchers found mutations in noncoding UCEs are frequent and broadly dispersed in many cancer types, whereas mutations in protein-coding UCEs tend to happen in hot spots – genomic areas where mutations are frequently found. Additionally, the loss of certain altered UCEs significantly impacted cancer cell proliferation. In-depth analyses showed that certain noncoding UCEs can either be enhancers of tumor suppressors or silencers of oncogenic proteins, emphasizing their diverse regulatory roles in cancer development. Further research is merited to explore the role of evolutionary noncoding DNA in cancer and other diseases. Learn more in Science Advances.
Cell-free HPV DNA is a potential biomarker for relapse in cervical cancer
Although chemoradiation is an effective treatment of cervical cancer, about 40% of patients will ultimately relapse, highlighting a need for new early biomarkers to identify patients most at risk. Human papillomavirus (HPV) is a significant cause of cervical cancer, leading Ann Klopp, M.D., Ph.D., and colleagues to investigate whether monitoring circulating HPV cell-free DNA (cfDNA) could be used as a potential biomarker. They examined 66 patients with locally advanced cervical cancer and found that lower levels of HPV cfDNA after treatment were linked to better disease-free survival rates. The study also showed that patients treated with an additional dose of therapeutic HPV vaccine had more rapid declines of cfDNA. These findings suggest that monitoring HPV cfDNA after chemoradiation could help tailor personalized treatment plans to improve outcomes. Learn more in Clinical Cancer Research.
Some patients with metastatic non-clear cell renal cell carcinoma may benefit from dual immunotherapy
Non-clear cell renal cell carcinomas (nccRCC) are a group of uncommon kidney cancers which, when metastatic, can be aggressive and have limited treatment options. While nivolumab plus ipilimumab is the standard of care first-line therapy for metastatic clear cell renal cell carcinoma, the most common type of RCC, there is limited data about the benefits of this regimen for patients with metastatic nccRCC. To address this, researchers led by Nizar M. Tannir, M.D., and Omar Alhalabi, M.D., evaluated the safety and efficacy of nivolumab plus ipilimumab in 55 patients with metastatic nccRCC, focusing on three histological types – papillary, chromophobe, and unclassified. Patients with papillary RCC showed favorable treatment outcomes compared to those with chromophobe or unclassified RCC. Sarcomatoid features were found in 20 patients on the study and were associated with higher response rates. The objective response rate across all three histologies with sarcomatoid features was 55%. Adverse events on this study were mangeable. The efficacy and safety of this dual immunotherapy regimen make it a promising option for patients with these rare kidney cancer types. Learn more in the Journal for ImmunoTherapy of Cancer.
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Read below to catch up on recent MD Anderson press releases.
MD Anderson researchers develop novel antibody-toxin conjugate UT MD Anderson and Texas Children’s Hospital Announce Joint Venture to End Childhood Cancer MD Anderson receives nearly $23 million in CPRIT funding for cancer research, faculty recruitment Scientists find new biomarker that predicts cancer aggressiveness Read this press release in the MD Anderson Newsroom.
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