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Mayo Clinic

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Impact of prior authorization for oncology medications on practices with majority rural patient populations.
McGovern, Emily , Troy, Jeanie, Hughes, Heidi, Nelson, Lisa , Yuan, R., Nelson, Kristina R., Perschke, Grant, Ticku, Jonathan, Kamboj, Jasmine , Pritchett, Joshua C. , Schroeder, Zachary, Troy, Jeanie, Hughes, Heidi, Nelson, Lisa, Nelson, Kristina R., Kelly, Benjamin, Soefje, Scott A. , Swenson, Wade T.

JCO Oncology Practice | October 7, 2025 | Volume: 21 | Issue: 10_suppl | Pages: 55-55

10.1200/op.2025.21.10_suppl.55 Get It

55 Background: Prior authorization (PA) processes are known to create administrative burdens and delays in care, but little is known about how these challenges impact rural oncology patients and practice settings. Methods: To understand the broad impact of prior authorization on rural oncology patients and practices, we conducted this study across three community oncology practices serving majority rural patient populations with distinct geography, healthcare infrastructure, and models of care. Sites included one critical access hospital system located in a highly-rural community (Lakewood Health System; Staples, Minnesota), a community-based hub-and-spoke hospital system-based practice located in a mid-sized community (Mayo Clinic Health System – Northfield; Northfield, Minnesota), and a standalone referral level III trauma center serving a highly rural patient base (Self Regional Healthcare; Greenwood, South Carolina). This retrospective cohort study examined all intravenous and subcutaneous cancer-directed therapy plans (no oral therapy) that required PA submission at these locations over a three-month period from October 1, 2024 to December 31, 2024. Results: 129 PA submissions were required during the study period. 82 were due to cancer-directed therapy agents (of which 14 were immunotherapy agents), and 47 were due to adjunctive therapies (of which 22, 16, and 9 were due to granulocyte stimulation, bone preservation, and anti-emesis agents, respectively). All 129 PA submissions ultimately resulted in approval of the desired medication or formulary-approved biosimilar. Delays from PA submission to approval ranged from 0 to 18 days. A total of 209 patient-days were delayed due to PA during the study period, which did not ultimately result in change of care or denial of care in any instance. Conclusions: At all sites included in this study, all PA submissions were eventually authorized. The PA process was found to introduce inconsistent and potentially avoidable delays for hundreds of patients and their care teams. These findings highlight the inefficiency of current PA processes among rural cancer populations and the practices that care for them, underscoring the need for ongoing efforts directed at state and federal PA reform.
Assessing the financial implications of translating oncology clinical trial informed consent forms in the U.S.
Mañana, Ana I. Velazquez, Florez, Narjust , Idossa, Damé , Patel, Shruti , Wang, Katarina , Florez, Narjust

JCO Oncology Practice | October 7, 2025 | Volume: 21 | Issue: 10_suppl | Pages: 53-53

10.1200/op.2025.21.10_suppl.53 Get It

53 Background: Language barriers affect millions in the US, where nearly 8% of individuals (~ 26 million) have limited English proficiency, making it harder to access, understand, and engage with healthcare services. As clinical trials enroll increasingly diverse participants, ensuring the accessibility and clarity of consent forms is critical. Understanding translation costs can improve budgeting and prevent enrollment delays for non-English-speaking participants. This study evaluates the costs of translating consent forms into three of the most widely spoken non-English languages in the U.S. Methods: In February 2025, we queried ClinicalTrials.gov to identify publicly available consent forms for phase 3 interventional trials in lung, breast, GI, & GU cancers from 2013–2024. In total, 18 consent forms were identified. The U.S. News top 20 U.S. cancer centers were contacted to identify commonly used certified translation companies. We obtained quotes from 8 IRB-certified agencies via online portal for Spanish, Simplified Chinese, and Tagalog translations. Results: The 18 informed consent forms were on average 14 pages long (range: 3-29 pages). Across the 8 translation companies, translating documents into Spanish (average price per document [$pD]: 1088.58) was cheaper than Chinese (average $pD: $1253.94, p < 0.001) and Tagalog (average $pD: $1399.07, p < 0.001). Costs varied significantly by company (p < 0.001). Quality assurance measures, including dual translation and proofreading, were included in 87.5% of quotes. The average turnaround time for translating one consent into 3 different languages was 4 business days (range: 2-8 business days). Conclusions: The cost of translating informed consent forms for oncology clinical trials varies significantly by language and translation company, with Spanish translations being the least expensive and Tagalog the most costly. While translation costs represent a small fraction of overall trial expenses, variability in pricing and turnaround times underscores the need for structured budgeting and standardized translation processes. Translations of informed consents should ideally be completed prior to trial initiation to avoid the delayed recruitment or exclusion of non-English speaking patients. Our results are valuable for researchers & sponsors involved in oncology clinical trials, helping them make informed decisions in budgeting regarding language translation services. Company ID Average $pD, Spanish Average $pD, Chinese Average $pD, Tagalog Spanish $pW Chinese $pW Tagalog $pW 1 840.11 1,054.07 1,054.07 0.16 0.20 0.20 2 1,109.63 1,553.49 1,775.41 0.22 0.28 0.32 3 945.00 1,081.50 1,422.33 0.10 0.17 0.12 4 1,880.56 1,880.56 2,131.94 0.30 0.30 0.34 5 875.35 875.35 875.35 0.15 0.15 0.15 6 1,029.98 1,367.56 1,472.93 0.27 0.36 0.39 7 929.72 978.65 1,125.45 0.14 0.15 0.17 8 1,042.39 1,184.50 1,279.22 0.33 0.37 0.41
Improving documented rates of comprehensive vaccination status assessment and vaccination recommendation in patients receiving chemotherapy at a breast medical oncology clinic.
Greenmyer, Jacob R. , Hoppenworth, Jenna, Huschka, David J., Volety, Rama, Taraba, Jodi L. , Tevaarwerk, Amyé , Volety, Rama , Taraba, Jodi L , Allen‐Rhoades, Wendy

JCO Oncology Practice | October 7, 2025 | Volume: 21 | Issue: 10_suppl | Pages: 431-431

10.1200/op.2025.21.10_suppl.431 Get It

431 Background: The National Adult and Influenza Immunization Summit (NAIIS) promoted clinical subspecialist efforts toward vaccination assessment and recommendation as one strategy to increase adult vaccination rates. Problem Statement: Between August 1, 2022, and May 31, 2023, 0% (n=0/100) of patients seen in medical oncology at Mayo Clinic (Rochester, MN) and receiving chemotherapy for breast cancer had a documented comprehensive vaccination status assessment by breast medical oncology staff. Aim Statements: (1) To increase the rate of comprehensive vaccination status assessment performed by breast medical oncology staff from 0% to 75% of patients receiving chemotherapy for breast cancer by September 2024. (2) To increase the rate of documented vaccination recommendation for patients who were not up to date with recommended vaccinations from 0% to 50% by September 2024. Methods: We deployed multiple interventions including physician and nurse education; development of patient education materials; and a standard operating procedure (SOP) for vaccination status assessment, vaccination recommendation, and vaccine-related documentation. Our SOP utilized an Epic SmartPhrase with following elements: (1) SmartLink that autopopulated overdue vaccinations, (2) hidden tip text permitting the use to hyperlink to Health Maintenance, (3) SmartLists that captured nurse actions (e.g., provided education) and encounter outcomes (e.g., patient endorsed plans to receive vaccinations), and (4) scripting for immunization education. Results: Multi-faceted interventions were associated with an improvement in the documented rate of comprehensive vaccination status assessment from 0% (n=0/100) to 82.8% (n=101/122). Most patients (77.2%, n=78/101) were not up to date with recommended vaccinations. Recommendations for appropriate vaccinations were made for 80.8% (n=63/78) of patients who were not up to date. Only 19.2% (n=15/78) of patients who were not up to date endorsed intention to receive missing/recommended vaccines. Counterbalance: Nurses were able to assess vaccination status and make appropriate recommendations in less than 5 minutes per patient. There was no difference in nurse-reported workflow burden related to vaccination status assessment, recommendation, or documentation after intervention. Conclusions: This quality project aligned our breast medical oncology practice with vaccination-related care promoted by NAIIS. We increased rates of vaccination status assessment and vaccination recommendations without impacting nurse-reported workflow burden. Medical subspecialty clinic engagement in vaccination efforts is feasible.
Utilizing EMR capabilities to improve shared decision-making regarding DPYD pharmacogenomic testing.
Sutton, Joseph , Jazieh, Khalid , Wright, Jessica , Jin, Zhaohui , Anderson, Benjamin O. , Hálfdánarson, Þorvarður R. , Tevaarwerk, Amyé

JCO Oncology Practice | October 7, 2025 | Volume: 21 | Issue: 10_suppl | Pages: 426-426

10.1200/op.2025.21.10_suppl.426 Get It

426 Background: Testing for DPYD gene variations prior to administration of fluoropyrimidines ([FP] e.g. 5-FU or capecitabine) can determine if patients are at risk of significant toxicity and may benefit from dose reduction or elimination of chemotherapy. Barriers to testing include lack of recommendations in US guidelines for routine DPYD testing, absence of insurance coverage, and limitations in provider support. We designed an electronic health record (EHR)-based intervention to support shared decision-making (SDM) between providers and patients regarding DPYD testing. Methods: We built an EHR alert identifying all patients initiating FP without DPYD testing. The alert fired to remind providers upon signing FP. Clinical decision support (CDS) was included in the alert to help with DPYD testing selection along with an educational note template containing the incidence of DPYD deficiency, rationale for testing, test costs, and turnaround time. Interactions with the EHR were recorded to determine why providers declined ordering pharmacogenomic testing. Testing rates and results for patients initiating FP were collected from the EHR. Finally, providers were surveyed to determine the impact of the alert on conversations with patients as well as the utility of the embedded CDS and educational note template. Results: Within the first 8 months after alert activation, 34 patients completed DPYD testing of 444 starting FP (testing rate of 7.7%) vs the baseline testing rate in the 3 months prior to alert go-live of 6.8% (p = 0.86 via chi-squared analysis, two-tailed). Of the 34 patients, 5 were intermediate DPYD metabolizers. Reasons for alert dismissal per provider selection were: “Patient already tolerated prior fluoropyrimidines” (15.7%), “Patient declines” (12.9%), “Will order separately” (5.7%), “Not discussed as not appropriate” (5.3%), and “Not discussed, deferred” (60.4%). Thirty-nine providers (n = 77 eligible) responded to the survey; 22 prescribed FP in their practice and had encountered the alert. 21 (95.5%) of these reported the alert was “Very Useful” or “Somewhat Useful” and 18 (81.8%) used the DPYD testing options available in the alert. Sixteen (72.7%) discussed DPYD testing more frequently with patients as a result of the alert. Barriers to DPYD testing were “Concerned about the impact of lowering FP dosing” and “Lack of knowledge about DPYD testing”, while “Cost of DPYD testing” was scored lowest. Conclusions: Utilizing an EHR alert with embedded CDS had a positive impact on provider awareness and led to more discussions regarding DPYD pharmacogenomic testing with patients in line with current FDA recommendations. Limitations in provider knowledge regarding DPYD testing and concerns about lowering chemotherapy doses posed barriers to ordering testing. Further interventions including additional education are required.
The growing burden of prior authorization: A national survey.
Gracie, Jayden , Sim, Austin J. , Gardner, Liz, Beatley, Emilio, Chen, Xuguang , Sharifzadeh, Yasamin , Winkfield, Karen M. , Chin, Alexander L. , Paravati, Anthony J., Luh, Join Y. , Barnes, Justin M. , Beatley, Emilio, Bates, James E. , Shen, Xinglei , Hong, David S. , Sio, Terence T. , Jimenez, Rachel , Chino, Fumiko

JCO Oncology Practice | October 7, 2025 | Volume: 21 | Issue: 10_suppl | Pages: 98-98

10.1200/op.2025.21.10_suppl.98 Get It

98 Background: Prior authorization (PA) purports to control costs and ensure adherence to evidence-based guidelines but negatively impacts cancer care. Radiation oncology (RO) represents a minority of overall cancer spending yet bears a disproportionately high PA burden. Limited research exists on the effects of PA on patient outcomes and administrative workload within RO clinics. Methods: From 9/2024 to 10/2024, an online survey was open to U.S. members of the American Society for Radiation Oncology assessing experiences with PA including disposition (approval/denial/appeal including peer-to-peer [P2P] review) and perceived impact on patient care and administrative workload. Outcomes included treatment delays, changes from recommended treatment, and patient event including hospitalization, ED visits, permanent disability, or death. Descriptive statistics evaluated responses. Results: Of 736 responding radiation oncologists (16% response rate), 83% reported a rise in PA over the past three years, with 58% noting the burden has increased greatly. In the past year, 50% reported that more than half of their cases required PA, with a median approval rate of 75% and median overturn rate of 82% for denials. For more than half of their cases, nearly half of physicians (43%) noted that P2P was a futile effort to overturn PA denials due to insurance policies. Most (75%) reported that PA resulted in their practice needing to reallocate staff; 91% reported worsening burnout due to PA. P2P reviews were particularly burdensome, averaging 1.65 hours per week. A third (30%) reported that PA requirements had caused serious complications for their patients, including 7% who reported PA had contributed to patient death. Almost all (91%) reported PA-related treatment delays for some of their patients, with 58% indicating average delays of ≥5 days. Most (81%) reported that at times they had to use radiation techniques they considered less optimal due to PA, including 58% who were forced to deviate from national guidelines. The most common reasons for not appealing a PA denial were anticipated delays (73%), perceived futility based on prior PA experiences (62%), and administrative burden (45%). Conclusions: The administrative and clinical burdens associated with PA have significant implications for patient care, physician well-being, and healthcare resource allocation in RO. Treatment delays, compromised therapies, and adverse patient outcomes are commonly reported and underscore the need for PA reform to improve patient outcomes, reduce physician burnout, and improve efficiency.
Impact of oncology second opinion consultation on anxiety levels and confidence in the organization.
Sullivan, Molly , Hellard, Sally, Jahanzeb, Mohammad , Leming, Philip D. , Randall, Marcus E. , Guinigundo, Andrew S, Hunt, Jillian M., Reid, Amanda, Smeltzer, Matthew, Zoň, Robin , Barrett, William , Jazieh, Abdul Rahman , Reid, Amanda, Jazieh, Khalid

JCO Oncology Practice | October 7, 2025 | Volume: 21 | Issue: 10_suppl | Pages: 406-406

10.1200/op.2025.21.10_suppl.406 Get It

406 Background: Anxiety is highly prevalent among oncology patients, often arising from uncertainty around diagnosis, treatment options, and prognosis. Elevated anxiety can impair decision-making, reduce treatment adherence, and diminish overall quality of life. Effective second opinion consultations may help mitigate anxiety and increase patients’ confidence in recommending healthcare services to others. Our study evaluates the impact of oncology second opinion (OSO) consultations on anxiety level (AL) and confidence in the organization (CIO) providing the second opinion, i.e., Cincinnati Cancer Advisors (CCA) and Naples Cancer Advisors (NCA). Methods: The study included patients with cancer diagnoses, age ≥18 years, who were served in person for OSO at CCA and NCA. A survey was used before and after consultation, measuring AL (scale 1- 10) and CIO level (scale 1 - 10), assessed by asking patients how likely they would refer loved ones to the organization. After the content and face validation, patients completed the survey anonymously, put it in a sealed envelope, and dropped it in a dedicated box. Data was analyzed using paired t-tests to compare the change from pre- to post-consultation scores. Spearman’s correlation test was used to assess the relation between the changes in AL and CIO. Statistical significance was assessed using an alpha-level of 0.05. Analyses were conducted via R and R Studio (version 2025.5.1.513). Results: Overall, 46 consecutive patients participated (45 completed AL pre and post visit survey and 43 completed the CIO pre and post visit survey). The mean pre-consultation anxiety score was 5.92 (SD = 2.58), and the post-consultation score was 3.87 (SD = 2.10), demonstrating a significant reduction (mean paired difference = -2.05; p < 0.0001). The mean pre-consult CIO was 8.21 (SD = 2.03), increasing to 9.73 post-consultation (SD = 0.53), indicating a significant improvement (mean paired difference = 1.66; p < 0.0001). The correlation between changes in AL and CIO was not statistically significant, which may be attributed to the high baseline CIO scores (ceiling effect) and the small sample size. Conclusions: Oncology second opinion was associated with a marked decrease in patient AL and a significant increase in CIO. The patient survey will continue to recruit additional participants to increase the sample size and explore the correlation between changes in AL and CIO. Studying the downstream impact on patient experience and outcome is warranted.
Financial and clinical implications of protein energy malnutrition on hospitalized patients with colorectal cancer: Trends from the National Inpatient Sample.
Syal, Arshi , Arya, Yajur , Ratnani, Akshay, Jones, Colton , Casipit, Carlo, Batra, Nitya, Varadi, Gàbor, Mahadevia, Himil

JCO Oncology Practice | October 7, 2025 | Volume: 21 | Issue: 10_suppl | Pages: 34-34

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34 Background: Colorectal cancer is the third most common cancer worldwide. Newer treatment options have significantly improved quality of life in these patients, albeit with the potential for more adverse effects. Patients with colorectal cancer tend to have varying degrees of protein energy malnutrition (PEM) due to multiple reasons, including cancer-related cachexia, sarcopenia, and adverse effects of chemotherapy. Therefore, the impact of PEM on outcomes among patients with colorectal cancer needs further exploration. Methods: We utilized the 2020 National Inpatient Sample (NIS) Database in conducting this retrospective cohort study. We identified patients with colorectal cancer and PEM using appropriate ICD-10 diagnostic codes. We stratified patients with colorectal cancer based on the presence or absence of PEM. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of < 0.05 was considered statistically significant. The aim of this study was to investigate the impact of PEM on in-hospital mortality, hospital length of stay (LOS), and total hospitalization charges among patients with colorectal cancer. Results: We identified a total of 77130 hospitalized patients with colorectal cancer, of which 11.06% (8535/77130) had comorbid PEM. The overall in-hospital mortality among patients with colorectal cancer was 2.74% (2115/77130). Among those with concomitant PEM, the mortality rate was significantly higher at 8.03% (686/8535, p < 0.001). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and level confounders, PEM was found to be an independent predictor of increased in-hospital mortality (adjusted OR 2.94; 95% (confidence interval [CI] 2.26-3.81; p < 0.001), longer LOS (coefficient 5.37 days; CI 4.84-5.90; p < 0.001), higher total hospitalization charge ($53844; CI $45188-$62499; p < 0.001), increased need for mechanical ventilation (adjusted OR 3.87; CI 2.96-5.06; p < 0.001), and increased need for renal replacement therapy (adjusted OR 2.20; CI 1.08-4.50; p = 0.029). Conclusions: Our analysis demonstrated that PEM was widely prevalent in hospitalized patients with colorectal cancer and was associated with significantly higher in-hospital mortality and longer length of hospitalization. PEM was also associated with a significantly higher cost of healthcare utilization, increased need for mechanical ventilation and renal replacement therapy. A proactive approach to promote nutritional assessment and early nutritional optimization is indicated. Further prospective studies are needed to better understand the impact of nutritional optimization on the financial burden as well as short and long-term outcomes in this patient population.
Heterogeneity in Racial and Ethnic Disparities in COVID-19 Severity Among Pediatric Inpatients in a National Healthcare Database
Watson, David , Spaulding, Alicen B. , Norton, L. J. , Norton, Laura

Journal of the Pediatric Infectious Diseases Society | October 7, 2025 | Volume: 14 | Issue: 10 | Pages: No page available

10.1093/jpids/piaf092 | PMID 41060298 Get It

Abstract Background The COVID-19 pandemic magnified longstanding racial and ethnic disparities in pediatric health, but it is unclear which populations experienced the largest disparities. Our objective was to determine whether disparities in COVID-19 severity differed with respect to patient factors analyzed as effect modifiers. Methods Using data from the Premier Healthcare Database, this retrospective cohort study included encounters among inpatients &lt; 19 years old from April 2020 through September 2022 in the USA with a COVID-19 diagnosis. Outcomes of COVID-19 severity were intensive care unit (ICU) admission and ventilator use. Comparisons between Black and White patients and Hispanic and White patients were adjusted for confounders using propensity score weights, reported as risk differences (RDs) in percentage points, and tested for heterogeneity (interaction P) across subgroups of effect modifiers such as complex chronic conditions (CCCs) and insurance status. Results Of 8947 pediatric inpatients with primary COVID-19 diagnosis, 3858 were White, 2153 were Black, and 2936 were Hispanic. Among children with a CCC, 14.3% of Black inpatients required a ventilator compared to 9.8% of White inpatients; among children without a CCC, 3.2% of both Black and White inpatients required a ventilator (RDs 4.5 vs 0.0; interaction P = .013). Comparisons of Hispanic and White inpatients showed a similar trend in ventilator use, with larger disparities among inpatients with CCCs and no difference among those without CCCs (RDs 2.7 vs −0.7; interaction P=.031). Among children with government insurance, 25.9% of Black inpatients were admitted to the ICU compared to 20.8% of White inpatients; among children with private insurance, Black and White inpatients had comparable ICU admission rates of 20.0% and 21.4%, respectively (RDs 5.1 vs −1.4; interaction P = .025). Conclusions Among hospitalized children, racial and ethnic disparities in COVID-19 severity were largest for those with CCCs or government insurance. These results can help identify target populations for interventions to reduce inequity.
Imposter in the brain: aetiological, clinical and neuroimaging characteristics of Capgras syndrome
Hiroyuki, Watanabe , Whitwell, Jennifer L. , Bhaskaran, Jerusha G, Lowe, Val J. , Josephs, Keith A. , Watanabe, Hiroyuki , Bhaskaran, Jerusha G

Brain | October 7, 2025 | Volume: 149 | Issue: 4 | Pages: 1224-1238

10.1093/brain/awaf378 | PMID 41059767 Get It

Abstract Capgras syndrome is a delusional misidentification syndrome characterized by the recurrent belief that someone, usually a family member, has been replaced by an impostor. Although described over a century ago, its aetiology, clinical features and neuroimaging characteristics remain poorly understood due to its rarity. This study aimed to clarify these aspects through the analysis of a large cohort and to explore its clinical implications and underlying mechanisms. We conducted a retrospective cohort study by reviewing medical records of patients diagnosed with Capgras syndrome at the Mayo Clinic (Rochester, MN) over a 28-year period (January 1995 to December 2022). Clinical, neuropathological and neuroimaging data were analysed. A total of 204 patients were included (median age at onset: 73 years; 44% female). Twelve patients underwent neuropathological examination, all of whom exhibited α-synuclein pathology, including one patient with a clinical diagnosis of Alzheimer’s disease (AD). Regarding clinical diagnoses, neurodegenerative diseases were the most common (69%, n = 140), with dementia with Lewy bodies (DLB) being predominant (58%, n = 118), followed by mixed aetiologies (‘two-hits’) (18%, n = 36) and AD (10%, n = 21). Psychotic disorders accounted for 9% (n = 18) of cases. No case was attributed to a single stroke, although 9% (n = 19) involved coexisting cerebrovascular disease in the context of AD or DLB. In DLB, the timing of Capgras syndrome onset varied: it occurred later than cognitive decline and core clinical features (e.g. visual hallucinations, fluctuating cognition, parkinsonism) in both DLB and mild cognitive impairment-onset prodromal DLB, but earlier in psychiatric-onset prodromal DLB. In both DLB and AD, Capgras syndrome typically targeted a single spouse, whereas in psychotic disorders, it often involved multiple, non-spousal targets. Depression or anxiety was present in 55% (n = 112). Capgras syndrome worsened in the evening or at night (87%, n = 45/52), suggesting a link to negative affective states. Among 82 patients with DLB and AD treated with cholinesterase inhibitors, 15% (n = 12) showed symptomatic improvement. Neuroimaging with MRI and 18F-fluorodeoxyglucose-PET revealed widespread bilateral cortical involvement and prominent right frontal dysfunction in DLB and AD. Capgras syndrome is associated with DLB and could serve as a potential early diagnostic clue. Recognizing its phenomenological features—the number and type of targeted individuals—can help differentiate between neurodegenerative and psychiatric aetiologies. In neurodegenerative diseases, Capgras syndrome may reflect a multifactorial, dynamic process, driven by widespread bilateral cortical dysfunction (particularly involving the right frontal lobe) and psychological factors. Thus, a combined approach involving pharmacological and non-pharmacological interventions may offer effective management strategies.
Breaking down glioma primary cilia disassembly
Sarkisian, Matthew R. , Breunig, Joshua J. , Deleyrolle, Loic P. , Breunig, Joshua J

Neuro-Oncology Advances | October 7, 2025 | Volume: 7 | Issue: 1 | Pages: No page available

10.1093/noajnl/vdaf217 | PMID 41624424 Get It

Abstract While many postmitotic cells in the body harbor cilia, certain aggressive cancers such as glioblastoma (GBM) display low frequencies of cells harboring a primary cilium. Ciliated GBM cells that plan to multiply have to disassemble their cilium in order for centrioles to duplicate and re-purpose for mitosis. Little is known about the molecular mechanisms underlying cilia disassembly in GBM, or whether this may represent a driving factor in disease onset, progression, or recurrence. In many cell types, ciliary disassembly is thought to be orchestrated by the aurora kinase A (AURKA) and histone deacetylase 6 (HDAC6) signaling axis. These molecules are often overexpressed in GBM, perhaps owing to the less frequent observation of ciliated GBM cells. Here, we review regulators of the core pathway, and discuss recent studies attempting to inhibit AURKA and HDAC6 in patient and mouse models of GBM and resulting effects on cilia. In the face of potent inhibitors, GBM cells appear to engage pathways independent of the core axis to promote cilia disassembly and/or engage other forms of modified axonemal tubulin to ensure persistence of cilia on GBM cells. GBMs upregulate a host of proteins implicated to drive cilia disassembly. Thus, clarifying these alternate mechanisms may be important as the roles of cilia in tumor formation and propagation, angiogenesis, and treatment resistance are increasingly reported. A deeper understanding of the role of cilia in these hallmarks of glioma may hold clues to the high recurrence rate of GBM.