Header: Scite.ai autogenerates short, fully referenced articles on the topic of your choice, even kind of obscure ones. If you think "AI writing is unusable because of hallucinations," you haven't used Scite.ai.
Here, I update an April 2024 blog.
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I've referred before to a subscription AI service called SCITE.AI. When you have an index paper (Smith et al. 2022), it gives you all the papers that have cited it, AND, in most cases, the paragraph of text that makes the citation.
You get other data, like how many citations a paper has, how many are neutral citations, which citations are confirmatory vs negative, etc. Click on any paper citing Smith et al. 2022, or any paper in the bibliography of Smith et al. 2022, and replicate the same info instantly.
SCITE has full-text access to all public articles, plus licenses that allow it to present short quotes even from many firewalled articles.
Assistant by SCITE
Scite.ai has got another trick called ASSISTANT BY SCITE. Here, you give it a question or a topic, and it searches PubMed for relevant articles and builds an AI summary out of them.
POLE?
Someone asked me about the gene, POLE (dna polymerase epsilon), which contributes to hypermutations in some cancers. New to me. I checked the AMA CPT codebook, and while there are codes that mention POLG and POLG2 (gamma and gamma-2), nothing for POLE.
I gave this request to ASSISTANT BY SCITE:
"What are the clinical purposes in clinical oncology
for testing the gene POLE?"
In about a minute, it rolled back with this response.
Testing the gene POLE in clinical oncology serves several important purposes. POLE mutations have been identified in various cancers, including colorectal cancer, endometrial cancer, and lung adenocarcinoma. Detecting pathogenic variants in the POLE gene is crucial for identifying patients with a good prognosis and guiding treatment decisions (Heerik et al., 2023). In endometrial cancer, POLE mutations are associated with a favorable outcome and high PD-L1 expression, indicating a potential benefit from immunotherapy (Liu et al., 2018). Furthermore, POLE mutations have been linked to increased tumor mutation burden (TMB) and have shown promise in predicting response to immune checkpoint inhibitors (Li et al., 2022).
The clinical significance of POLE mutations extends to different cancer types, such as colorectal cancer and stomach adenocarcinoma. POLE mutations have been associated with distinct clinicopathological characteristics and outcomes, emphasizing the importance of distinguishing POLE category tumors for tailored management (Hino et al., 2019). Additionally, assessing POLE and POLD1 mutations in stomach adenocarcinoma has been proposed as a valuable prognostic and immunotherapy biomarker (Zhu et al., 2022).
Moreover, POLE mutations have implications beyond prognosis and treatment response. Studies have highlighted the role of POLE mutations in activating cancer-cell-intrinsic immunity and suppressing tumorigenesis through specific pathways (Tang, 2024). Furthermore, the identification of germline POLE mutations in pediatric patients with hypermutated medulloblastoma underscores the importance of genetic testing for early detection and management of hereditary cancer syndromes (Lindsay et al., 2019).
In conclusion, testing for POLE mutations in clinical oncology is essential for risk assessment, treatment stratification, and predicting response to immunotherapy across various cancer types. Understanding the clinical implications of POLE mutations can aid in personalized cancer care and improve patient outcomes.
References:
Heerik, A., Haar, N., Vermij, L., Jobsen, J., Brinkhuis, M., Roothaan, S., … & Bosse, T. (2023). qpole: a quick, simple, and cheap alternative for pole sequencing in endometrial cancer by multiplex genotyping quantitative polymerase chain reaction. Jco Global Oncology, (9). https://doi.org/10.1200/go.22.00384
Hino, H., Shiomi, A., Kusuhara, M., Kagawa, H., Yamakawa, Y., Hatakeyama, K., … & Yamaguchi, K. (2019). Clinicopathological and mutational analyses of colorectal cancer with mutations in the pole gene. Cancer Medicine, 8(10), 4587-4597. https://doi.org/10.1002/cam4.2344
Li, S., Zhang, J., Du, W., Ren, X., & Zhang, X. (2022). Pathologic complete response to immune checkpoint inhibitor in a stage iiib ovarian clear cell carcinoma patient with pole mutation resistant to platinum-based chemotherapy: a case report. Gland Surgery, 11(9), 1562-1567. https://doi.org/10.21037/gs-22-420
Lindsay, H., Scollon, S., Reuther, J., Voicu, H., Rednam, S., Lin, F., … & Roy, A. (2019). Germline pole mutation in a child with hypermutated medulloblastoma and features of constitutional mismatch repair deficiency. Molecular Case Studies, 5(5), a004499. https://doi.org/10.1101/mcs.a004499
Liu, L., Ruiz, J., O’Neill, S., Grant, S., Petty, W., Yang, M., … & Zhang, W. (2018). Favorable outcome of patients with lung adenocarcinoma harboring pole mutations and expressing high pd-l1. Molecular Cancer, 17(1). https://doi.org/10.1186/s12943-018-0832-y
Tang, M. (2024). The p286r mutation of dna polymerase ε activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cgas-sting pathway. Cell Death and Disease, 15(1). https://doi.org/10.1038/s41419-023-06418-3
Zhu, M., Cui, H., Zhang, L., Zhao, K., Xing, J., & Jin, H. (2022). Assessment of pole and pold1 mutations as prognosis and immunotherapy biomarkers for stomach adenocarcinoma. Translational Cancer Research, 11(1), 193-205. https://doi.org/10.21037/tcr-21-1601
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Let's ask a follow up.
"Going back to the POLE gene, when it is mutated,
the cancer cell genome may be hypermutated.
It seems like hypermutated cancers may be good candidates for checkpoint inhibitor therapy. TMB, tumor mutational burden, is a marker for checkpoint inhibitor drug response.
Is there evidence that POLE itself, is a biomarker for better checkpoint inhibitor response?"
Among the references provided, Reference (Garmezy et al., 2022) by in "Clinical and Molecular Characterization of POLE Mutations as Predictive Biomarkers of Response to Immune Checkpoint Inhibitors in Advanced Cancers" stands out as a relevant source for investigating whether POLE mutations serve as biomarkers for improved response to checkpoint inhibitor therapy. This study delves into the association between mutations in the POLE exonuclease domain, hypermutated cancers, and the potential for enhanced responses to immunotherapy agents, suggesting a trend towards improved prognosis (Garmezy et al., 2022). The findings from this research shed light on the predictive value of POLE mutations in guiding treatment decisions involving immune checkpoint inhibitors, indicating a potential benefit for patients with POLE-mutated cancers.
Moreover, Reference Wang (2023) by et al. provides additional insights into the immune signatures of POLE mutations in endometrial carcinomas. The study demonstrates that tumors with POLE mutations exhibit significantly higher tumor mutational burden (TMB) and microsatellite instability (MSI) scores, suggesting a more favorable response to immune checkpoint inhibitors (Wang, 2023). This evidence further supports the notion that POLE mutations may serve as predictive biomarkers for better responses to immunotherapy, emphasizing the potential clinical implications of POLE status in guiding treatment strategies for cancer patients.
Furthermore, Reference Durando et al. (2022) by presents a case study highlighting a patient with POLE mutation-associated colorectal cancer who achieved a four-year disease-free remission following anti-PD-1 therapy. This case underscores the clinical significance of POLE mutations and their impact on treatment outcomes, particularly in the context of immune checkpoint blockade (Durando et al., 2022). The successful response to anti-PD-1 therapy in this case suggests that POLE mutations may indeed be associated with improved checkpoint inhibitor responses, supporting the hypothesis that POLE status could serve as a biomarker for favorable treatment outcomes.
In conclusion, the references provide compelling evidence suggesting that POLE mutations may serve as predictive biomarkers for better responses to immune checkpoint inhibitor therapy in various cancers. The studies highlight the association between POLE mutations, hypermutated phenotypes, increased TMB, and enhanced antitumor immune responses, indicating the potential utility of POLE status in guiding immunotherapy strategies for cancer patients.
[Additional citations omitted].
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Find A Review Article
Here I asked for a POLE review article. The third one, YAO, sounds like that most on-point. Even though HEERIK is about technology, it might have a good overview about why you'd bother to test POLE in cancer patients. A side bar in the SCITE reference sections tells me that each of these is "open access."
"Find review articles about the gene POLE (dna polymerase epsilon) in clinical oncology. Focus on 2022, 2023, 2024 papers."
The references provided focus on the clinical characteristics, detection, and sequencing of POLE mutations in endometrial cancer. They offer valuable insights into the significance of POLE mutations in endometrial carcinoma, emphasizing the importance of accurate detection and characterization for improved clinical management and treatment outcomes.
- Heerik, A., Haar, N., Vermij, L., Jobsen, J., Brinkhuis, M., Roothaan, S., … & Bosse, T. (2023). qpole: a quick, simple, and cheap alternative for pole sequencing in endometrial cancer by multiplex genotyping quantitative polymerase chain reaction. Jco Global Oncology, (9). https://doi.org/10.1200/go.22.00384
- Lawson, N. and Chung, B. (2023). Clinical characteristics and detection of polymerase epsilon mutant endometrial carcinoma. Science Insights, 42(4), 903-908.
- https://doi.org/10.15354/si.23.re295
- Yao, X. (2024). The clinical and pathological characteristics of pole-mutated endometrial cancer: a comprehensive review. Cancer Management and Research, Volume 16, 117-125. https://doi.org/10.2147/cmar.s445055
Here's another one, from the headlines.
ALZ blood tests.
I understand there have been big advances in the accuracy of TAU and other BLOOD tests for Alzheimer diagnosis. Please review this topic focusing on 2023 and 2024 papers.
In recent years, there has been a significant advancement in the accuracy and utility of blood tests for diagnosing Alzheimer's disease (AD), particularly focusing on biomarkers like tau and amyloid-beta (Aβ) proteins. The development of blood biomarker tests for AD has progressed rapidly, with these tests now being increasingly utilized in research studies, clinical trials, and clinical practice (Hansson et al., 2023). Detecting readily available blood biomarkers such as Aβ42 peptides, phosphorylated tau proteins, and total tau proteins has emerged as a promising strategy for AD diagnosis (Abukuri, 2024). These accessible blood tests measure biomarkers associated with AD pathology, including amyloid-beta and tau, which are key features of the disease, along with assessing neurodegeneration (Warmenhoven, 2024).
Recent studies have highlighted the shift from low-sensitive plasma assays to new ultra-sensitive assays like single molecule enzyme-linked immunosorbent assay (Simoa), the Mesoscale Discovery (MSD) platform, and immunoprecipitation-mass spectrometry (IP-MS) for determining plasma biomarkers of AD with higher accuracy (Pais et al., 2023). The accurate detection of AD pathology, including Aβ plaques and hyperphosphorylated tau aggregates, through blood tests is crucial for both research and clinical trials, with implementation in clinical settings already underway (Colvee-Martin, 2024).
Plasma biomarkers, especially phosphorylated-tau217 (p-tau217), have shown utility in screening and diagnosing the earliest stages of AD (Datta, 2024). Plasma pT217‐tau, among multiple tau species and other biomarkers, has demonstrated high accuracy in predicting the presence of AD neuropathology, including aggregated tau pathology (González‐Ortiz et al., 2023). Additionally, plasma phosphorylated tau (p-tau) has shown specificity to AD compared to non-AD neurodegenerative diseases, making it a valuable biomarker for clinical diagnosis and eligibility for approved therapies (Kac, 2023).
The development of blood biomarkers targeting the principal pathological hallmarks of AD, such as Aβ and p-tau, has provided new diagnostic and prognostic opportunities that were not feasible with cerebrospinal fluid (CSF) or neuroimaging biomarkers (Garcia-Escobar, 2024). These blood-based biomarkers hold great promise to revolutionize the diagnostic and prognostic work-up of AD in clinical practice (Hansson et al., 2023). Recent advances in blood-based biomarkers offer a less invasive alternative to current CSF measures, enhancing the feasibility of widespread screening and monitoring for AD (Garcia-Escobar, 2024).
In conclusion, the advancements in blood tests for AD, particularly focusing on tau and Aβ biomarkers, have significantly improved the accuracy and accessibility of AD diagnosis. These blood-based biomarkers offer a less invasive and more practical approach to screening, diagnosing, and monitoring AD, with the potential to revolutionize the field of AD research and clinical practice.
Abukuri, D. (2024). Novel biomarkers for alzheimer’s disease: plasma neurofilament light and cerebrospinal fluid. International Journal of Alzheimer S Disease, 2024, 1-15. https://doi.org/10.1155/2024/6668159 Datta, D. (2024). Nanoscale imaging of pt217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: evidence of interneuronal trafficking and early‐stage neurodegeneration. Alzheimer S & Dementia, 20(4), 2843-2860. https://doi.org/10.1002/alz.13737
Garcia-Escobar, G. (2024). Blood biomarkers of alzheimer’s disease and cognition: a literature review. Biomolecules, 14(1), 93. https://doi.org/10.3390/biom14010093
González‐Ortiz, F., Kac, P., Brum, W., Zetterberg, H., Blennow, K., & Karikari, T. (2023). Plasma phospho-tau in alzheimer’s disease: towards diagnostic and therapeutic trial applications. Molecular Neurodegeneration, 18(1). https://doi.org/10.1186/s13024-023-00605-8
Pais, M., Forlenza, O., & Diniz, B. (2023). Plasma biomarkers of alzheimer’s disease: a review of available assays, recent developments, and implications for clinical practice. Journal of Alzheimer S Disease Reports, 7(1), 355-380. https://doi.org/10.3233/adr-230029
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SCITE writes about "tests that report intermediate zones."
