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  • Understanding resistance to EGFR targeted therapies in head and neck cancers and breast cancer

    Understanding resistance to EGFR targeted therapies in head and neck cancers and breast cancer

    A new review was published in Volume 16 of Oncotarget on June 25, 2025, titled “Challenges and resistance mechanisms to EGFR targeted therapies in head and neck cancers and breast cancer: Insights into RTK dependent and independent mechanisms.”

    Researchers from the University of Cincinnati and Cincinnati Veterans Affairs Medical Center reviewed current research on why Epidermal Growth Factor Receptor (EGFR)-targeted therapies often fail in breast and head and neck cancers. The article by Shreya Shyamsunder, Zhixin Lu, Vinita Takiar, and Susan E. Waltz explores how cancer cells evade these treatments by activating alternative survival pathways. This review offers an in-depth look at the molecular barriers to EGFR inhibition and provides insights that could inform the development of more effective and durable treatments.

    EGFR is a critical protein that regulates cell growth and survival, and it is frequently overexpressed in breast and head and neck cancers. Although therapies targeting EGFR showed early promise, resistance has become a significant challenge. In breast cancer, resistance mechanisms include the movement of EGFR from the cell surface into the nucleus, where it promotes DNA repair, as well as ligand-dependent activation that helps tumor growth despite therapy. In head and neck cancers, resistance often arises from inflammatory signaling through the TLR4-MyD88 pathway and the loss of tumor suppressor genes like PTEN, which allow cancer cells to bypass EGFR inhibition. The review also describes how tumor cells in both cancers commonly activate other receptor tyrosine kinases (RTKs), such as MET, AXL, and RON, to continue growing even when EGFR is blocked.

    By analyzing these resistance mechanisms, the authors highlight combination therapies from current research that target EGFR and other key molecular pathways. Strategies such as dual inhibition of EGFR and MET or blocking inflammation-driven survival signals may enhance treatment outcomes. Several clinical trials are evaluating these approaches in patients. For example, in breast cancer, combinations of EGFR inhibitors with chemotherapy and immune checkpoint inhibitors are being tested to improve responses, particularly in triple-negative breast cancer. In head and neck cancers, trials are investigating EGFR-blocking antibodies like cetuximab combined with immunotherapies such as pembrolizumab and nivolumab. These efforts aim to overcome resistance and provide more effective treatment options for patients with EGFR-driven tumors. The review also emphasizes the necessity of identifying biomarkers to predict which patients are most likely to benefit from EGFR-based therapies.

    “A recent phase 1 study has shown that patients with recurrent or metastatic head and neck cancer who received BCA101, a bifunctional dual targeting drug that targets EGFR and TGF-β in combination with pembrolizumab, were able to achieve an overall response rate of 65%.“

    This work brings together current knowledge about EGFR resistance and illustrates the difficulties involved in treating breast and head and neck cancers. By mapping the many ways tumors overcome EGFR inhibition, the review highlights opportunities for more tailored and effective treatments in the future.

    Source:

    Journal reference:

    Shyamsunder, S., et al. (2025). Challenges and resistance mechanisms to EGFR targeted therapies in head and neck cancers and breast cancer: Insights into RTK dependent and independent mechanisms. Oncotarget. doi.org/10.18632/oncotarget.28747.

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  • CISO’s guide to creating a cybersecurity board report

    CISO’s guide to creating a cybersecurity board report

    In today’s threat-dense digital environment, shareholders and the public expect corporate boards to understand cybersecurity issues and what they mean for the bottom line. Since 2023, the U.S. Securities and Exchange Commission has required public companies to disclose their boards’ cyber-risk oversight practices, given that such information might reasonably influence investor decisions.

    The SEC mandate elevates the importance of clear, concise and informative cybersecurity board reports. Far more than just satisfying regulatory requirements, these reports can guide strategic decisions, demonstrate cybersecurity governance and support risk-informed business continuity.

    Here are some suggestions for CISOs aiming to write compelling and compliant cybersecurity board reports.

    What is a cybersecurity board report?

    A cybersecurity board report is a document written by security leaders, usually the CISO or security team, for corporate directors. This document has three key goals:

    1. It gives corporate directors an overview of the organization’s security posture and cyber-risk outlook.
    2. It updates them on key security initiatives and investments.
    3. It provides strategic recommendations from the CISO.

    CISOs must write cybersecurity board reports in a language directors understand, translating complex technical information and relating it to business objectives.

    Why are cybersecurity reports to the board important?

    Boards are now expected to understand, interrogate and guide their organizations’ cybersecurity strategies to optimize business outcomes. But many corporate directors come to the table with little cybersecurity expertise and limited understanding of their organizations’ security programs.

    Clear, transparent and actionable cybersecurity reports give boards the information they need to understand cyber-risk as business risk and fulfill their oversight responsibilities.

    Clear, transparent and actionable cybersecurity reports give boards the information they need to understand cyber-risk as business risk and fulfill their oversight responsibilities. This strengthens both corporate resilience and stakeholder trust.

    Board reports also give CISOs the opportunity to grow their influence, advance their strategic agendas and bridge the gaps between their security programs and senior business leaders. A 2023 Harvard Business Review survey found just 69% of board members said they see eye to eye with their CISOs — a statistic that underscores the need for effective engagement with executive decision-makers.

    Key elements of a cybersecurity board report

    The board’s primary responsibility is to facilitate the company’s long-term financial success. As such, directors need a comprehensive, strategic overview of the organization’s security posture and cyber-risk outlook, rather than an in-the-weeds, tactical and operational play-by-play.

    With this in mind, consider organizing the cybersecurity board report into thematic sections, as follows.

    Executive summary

    Provide a brief overview of key insights, takeaways, recommendations and action items. The executive summary should tell a coherent story about the organization’s current cyber-risk outlook and what it means for business objectives.

    Cyber-risk overview

    Align the cyber-risk overview with the enterprise risk management program and contextualize it within broader enterprise risk narratives. Boards need, first and foremost, to understand how cyber-risk intersects with financial, operational and compliance risks to affect business outcomes.

    Outline key cyber-risks facing the organization — including those from third-party partners — and assess the effectiveness of existing controls. Include cyber-risk scenario analysis or stress test summaries to illustrate how cybersecurity influences business continuity and outcomes.

    To measure and track cyber-risk levels in board reports over time, consider the following mechanisms:

    Threat landscape

    Provide a high-level summary of the company’s threat environment, including emerging attack trends, major attacks on peer organizations and relevant geopolitical developments.

    Key risk metrics

    Present relevant key risk indicator (KRI) and key performance indicator (KPI) metrics, such as phishing success rates, intrusion attempts, vulnerability patching timelines and insider threat alerts.

    Be intentional about which KPIs and KRIs you include — share only those that you can directly connect to business objectives. Cybersecurity for cybersecurity’s sake should not be the aim, and superfluous data can overload the reader and distract from key takeaways.

    Incident response overview

    Summarize the organization’s incident response plan, including the thresholds and processes for board involvement. Outline the mechanisms through which the board learns of active cyberincidents, such as threat briefings, event dashboards and formal escalation protocols.

    Describe recent incidents, responses, outcomes and post-incident remediation efforts.

    Regulatory updates

    Flag any changes in cybersecurity laws or industry standards that could affect regulatory compliance or operational security. Note that, given the rapid evolution of the cybersecurity threat landscape, regulatory updates occur frequently, especially in tech-heavy states, such as California.

    CISOs at public companies should also include information relevant to SEC disclosure requirements, such as the following:

    • Oversight responsibility. Review which board entity — e.g., committee, subcommittee or individual director — is responsible for cybersecurity oversight. Typically, this falls to the risk committee, appropriately positioning cybersecurity as a business risk, not merely an IT issue.
    • Engagement frequency. Detail how often the board or its designated subgroup meets with the CISO. The best practice is quarterly board discussions, plus monthly meetings with the relevant — e.g., risk — committee. Additional meetings could be ad hoc, in the case of significant security incidents.

    Strategic initiatives

    Highlight progress on cybersecurity roadmap items, such as zero-trust implementation, cloud security posture improvements or third-party risk assessments.

    Illustrate how cybersecurity is embedded in business strategy, such as in M&A, digital transformation and supply chain risk evaluations.

    Board actions and recommendations

    Make any strategic recommendations and new budgetary requests, being sure to position them in terms of enterprise risk and business objectives. Include relevant resources, such as current and projected security investments, ROI, staffing levels, and other resource gaps and recommendations.

    Best practices for reporting cybersecurity to the board

    Consider the following best practices to make cybersecurity board reports as useful and influential as possible:

    • Focus on business risk. A risk-based approach ensures the report is relevant, comprehensible and useful to the board.
    • Be clear and concise. The typical corporate board juggles many competing priorities, leaving members limited time and attention to spend on any single topic. Therefore, an effective cybersecurity board report should be concise, focused and intuitively structured.
    • Include executive summaries. Present key findings and takeaways in an executive summary for quick and easy reference.
    • Use visuals. Use visuals, such as charts and graphs, to engage readers and illustrate key points.
    • Highlight trends. Build a coherent narrative about the state of security by noting key trends — in KRIs, KPIs, industry benchmarks and threat activity — and what they mean for the business.
    • Avoid technical jargon. Jargon and acronyms can alienate nontechnical board members and undermine the CISO’s influence at the executive level.
    • Report to the board quarterly. Best practice dictates that the board should formally discuss cybersecurity at least quarterly, with risk committee discussions monthly. Call additional meetings as necessary for significant incidents.
    • Document cybersecurity board engagement initiatives. Cybersecurity competency at the board level is no longer optional. Consider using the report to document ongoing board training initiatives, involvement in tabletop exercises and engagement with external cybersecurity experts.

    Get started with a free, downloadable cybersecurity board report template.

    Jerald Murphy is senior vice president of research and consulting with Nemertes Research. With more than three decades of technology experience, Murphy has worked on a range of technology topics, including neural networking research, integrated circuit design, computer programming and global data center design. He was also the CEO of a managed services company.

    Alissa Irei is senior site editor of Informa TechTarget’s SearchSecurity site.

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  • Musk, X to face trial in Don Lemon lawsuit alleging breach of contract

    Musk, X to face trial in Don Lemon lawsuit alleging breach of contract

    Elon Musk (L) & Don Lemon

    Reuters (L) | Getty Images (R)

    Ex-CNN anchor Don Lemon’s lawsuit against tech billionaire Elon Musk and his social network X over the cancellation of their partnership can proceed to trial, a San Francisco judge ruled this week.

    Musk’s team had tried to get the case moved to a Texas court and tried to convince the judge to strike the complaint altogether.

    Attorneys for Musk and X didn’t respond to a request for comment.

    In an order Tuesday, Judge Harold Kahn said Lemon and his attorneys plausibly alleged, among other claims, that X and Musk had committed “fraud by false promise” and that there was “an implied contract” between them.

    Lemon filed the suit in August 2024 after X canceled a partnership with the broadcast journalist a few hours after he taped a tense interview with Musk, who owns X. The interview preceded a planned premiere of Lemon’s new show on Musk’s social network.

    During the interview, Lemon pressed Musk on several contentious topics he had posted about or amplified on X. Musk had boosted the so-called “great replacement theory,” and other bigoted tropes and falsehoods, including posts that claimed there was a “Hispanic invasion” of immigrants to the U.S.

    Lemon also pressed Musk about content moderation on X, and a reported surge in antisemitic content on the platform that occurred after Musk acquired it as Twitter in a $44 billion leveraged buyout in late 2022.

    Musk made sweeping changes after taking over the site, firing huge numbers of personnel and reversing account bans for users who had been booted from the platform after posting hate speech or inciting violence.

    Musk, who characterized himself as a free speech “absolutist” also restored the account of President Donald Trump. The site had permanently banned Trump from the platform in January 2021 following the attack by his supporters on the U.S. Capitol.

    Lemon’s case against Musk and X Corp. is in San Francisco Superior Court. A date has not been set for the trial.

    Musk and X have faced a litany of other lawsuits over non-payment to vendors and over failure to provide severance as promised to laid-off employees from Twitter.

    Lemon was fired from CNN in 2023 following reports that he mistreated coworkers and made sexist remarks on-air, including about politician Nikki Haley. Lemon later apologized for the Haley comments.

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  • Early Release – Progression from Candida auris Colonization Screening to Clinical Case Status, United States, 2016–2023 – Volume 31, Number 8—August 2025 – Emerging Infectious Diseases journal

    Early Release – Progression from Candida auris Colonization Screening to Clinical Case Status, United States, 2016–2023 – Volume 31, Number 8—August 2025 – Emerging Infectious Diseases journal

    Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.


    Author affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA

    Candida auris, an emerging, frequently antifungal-resistant yeast, can colonize patients asymptomatically and persist on skin for months to years without causing infection (1–3). Patients colonized with C. auris can progress to having invasive infections, which are associated with crude mortality rates of 30%–72% (4,5). Because C. auris spreads easily in healthcare settings, the Centers for Disease Control and Prevention (CDC) recommends colonization screening for patients with high-risk healthcare exposures (e.g., recent stay in a long-term acute-care hospital [LTACH] or ventilator-capable skilled nursing facility [SNF]) and those with an epidemiologic link to a patient with C. auris (2,6) (https://www.cdc.gov/candida-auris/hcp/screening-hcp).

    Data characterizing the progression from C. auris colonization to invasive disease are limited but might help guide public health surveillance, prevention, and treatment efforts. We analyzed US national case-based surveillance data to characterize patients with positive C. auris screening results who were subsequently found to have a positive clinical specimen.

    C. auris is a nationally notifiable condition, but reporting mandates vary across states and jurisdictions. State and jurisdictional health departments report C. auris screening and clinical cases to CDC. Screening cases were defined as a positive C. auris laboratory result from a swab sample (usually composite axilla/groin) collected to test for colonization. Clinical cases were defined as a positive C. auris laboratory result from a clinical specimen collected to determine the cause and treatment for infection in a patient. Clinical cases might involve body sites typically associated with invasive infection (e.g., blood) or those that potentially reflect colonization (e.g., urine) (https://ndc.services.cdc.gov/case-definitions/candida-auris-2023). Screening and clinical case data included information on patient age and sex, as well as date and facility type of specimen collection. Facility location was grouped by Antimicrobial Resistance Laboratory Network region (n = 7) (https://www.cdc.gov/antimicrobial-resistance-laboratory-networks/php/about/domestic.html). We used a patient-level identifier to link each patient’s screening case with a clinical case, if one occurred. We considered patients with a clinical case >1 calendar day after a screening case to have a screening-to-clinical (StC) event.

    The analysis includes each patient’s screening case on the basis of their first positive screening result (StC and non-StC events) and clinical case on the basis of first positive clinical specimen (StC events only) during 2016–2023. We calculated total and annual percentages of patients with screening cases who had StC events and described available data on non-StC events and StC events, stratifying by StC event status and examining StC events by body site involved. We analyzed categorical data using χ2 tests and continuous data using Kruskal-Wallis rank-sum tests (α = 0.05).

    Figure 1

    Figure 1. Number of patients with a Candida auris screening case and percentage who had progression to a clinical case, United States, 2016–2023. StC, screening-to-clinical.

    During 2016–2023, a total of 36 of 40 reporting jurisdictions reported 21,195 patients who had a positive screening result; of those, 1,458 (6.9%) patients across 22 jurisdictions had an StC event (2.8% blood, 4.1% nonblood) (Table 1). The number of patients with screening cases increased each year, and the percentage of those with an StC event increased from 0.0% (0/13) in 2016 to 9.9% (129/1,299) in 2020, then decreased to 4.9% (365/7,493) in 2023 (Figure 1).

    Among patients with screening cases (n = 21,195), the median age was 68 (interquartile range [IQR] 58–76) years; of those with known sex (n = 16,446), 9,448 (57.4%) were men and 6,998 (42.6%) were women (Table 1). The most common regions of screening case specimen collection were the West (31.2%, n = 6,617), Midwest (20.1%, n = 4,264), and Southeast (20.0%, n = 4,235) and the most common facility types among those with known facility type (n = 17,357) were LTACH (50.2%, n = 8,716), acute care hospital (ACH) (29.0%, n = 5,033), and ventilator-capable SNF (16.8%, n = 2,912). StC event frequency was similar by age (p = 0.650) and sex (p = 0.478) and varied by region (p<0.001), and facility type (p<0.001). StC event frequency was similar between women (7.4%) and men (7.1%) and was greatest among patients with screening specimens collected in the West (13.6%), Northeast (8.5%), Mid-Atlantic (4.3%), or Mountain (4.3%) regions. StC events were most frequent for patients with screening specimens collected in LTACHs (10.4%), then ACHs (5.9%), ventilator-capable SNFs (5.2%), non–ventilator-equipped SNFs (2.7%), and other facility types (1.9%).

    Figure 2

    Facility type of specimen collection for patients with Candida auris screening cases in whom clinical C. auris cases occurred, United States, 2016–2023. Sankey diagram made in RStudio (https://www.rstudio.com). ACH, acute care hospital; LTACH, long-term acute-care hospital; SNF, skilled nursing facility (non–ventilator-equipped); vSNF, ventilator-equipped skilled nursing facility.

    Figure 2. Facility type of specimen collection for patients with Candida auris screening cases in whom clinical C. auriscases occurred, United States, 2016–2023. Sankey diagram made in RStudio…

    Among StC events (n = 1,458), blood (40.1%, n = 584) and urine (26.8%, n = 391) were most common (Table 2); the distribution of affected body sites was generally similar across years (Appendix Figure). Body sites of clinical cases varied by age (p = 0.023), sex (p<0.001), region (p<0.001), and time from screening case to clinical case specimen collection (p = 0.001) (Table 2). Among women, blood specimens were approximately twice as common as urine (42.6% vs. 21.5%), whereas among men, the percentage was similar (32.0% vs. 32.2%). Blood specimens constituted most StC events in the Southeast (58.9%), Northeast (58.6%), and Mid-Atlantic (57.8%) regions but less than half of specimens in other regions. The median number of days from initial screening case specimen to clinical specimen was longest for blood (58, IQR 22–130, range 1–1,309 days) and shortest for respiratory (33, IQR 17–74, range 1–1,240 days) and other (28, IQR 14–77, range 1–745 days) specimen types. The most common facility types of initial screening case detection were LTACHs (62.2%) and ACHs (20.5%) (Figure 2). Regardless of the facility type where the screening case was detected, most StC events were detected in an LTACH (45.6%) or ACH (46.0%).

    This analysis of national C. auris case data revealed that, among 21,195 patients who tested positive for C. auris on a colonization screening swab during 2016–2023, a clinical case subsequently occurred in 6.9% (2.8% involving blood); more than half of clinical cases involving blood were detected 2 months after screening case detection. This finding is comparable with a smaller New York state study in which a C. auris bloodstream infection occurred in 7/187 (3.7%) colonized patients (median time from screening case testing to infection 86 days) (7).

    The percentage of patients with an StC event peaked in 2020 then declined, potentially because of improved infection prevention and control efforts or increased screening after COVID-19–related resource strains resolved. The volume of screening cases and frequency of clinical cases was greatest in the West, but the region had a relatively low percentage of clinical cases involving blood; that finding might reflect regional differences in case reporting and in testing practices for C. auris in noninvasive body sites (8). Most StC events were identified in LTACHs and ACHs, underscoring the continued need for focused screening, enhanced surveillance, and efforts to improve infection prevention and control implementation in these settings.

    For several reasons, we suspect that our study underestimates the actual percentage of patients with C. auris colonization who progress to having a clinical case. StC events could have been missed because of missed screening opportunities, the insensitivity of culture (9), treating clinical laboratories that might not routinely distinguish C. auris from other Candida species for nonsterile specimen types (10), and the fact that US C. auris data from 2024 are not finalized, meaning some patients might not have had sufficient lead time for clinical cases to occur. In addition, for clinical cases, we lacked data on previous negative screening results, the differentiation between infection and colonization, and underlying patient conditions.

    Overall, our study highlights the potential for C. auris infections, particularly candidemia, among patients colonized with C. auris. Rigorous infection prevention and control remain necessary to prevent the spread of C. auris and subsequent clinical infections. Further studies could investigate risk factors and strategies to prevent invasive C. auris infections among patients with colonization (e.g., through patient decolonization).

    Ms. Baker is an epidemiologist with the Mycotic Diseases Branch, Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. Her research interests include the epidemiology and prevention of fungal infections.


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  • List of missing in Texas floods adds uncertainty to search for survivors – Reuters

    1. List of missing in Texas floods adds uncertainty to search for survivors  Reuters
    2. Why did the Guadalupe River flood so fast? What to know about Texas’ ‘Flash Flood Alley’  Austin American-Statesman
    3. Kerr County has an emergency alert system. Some residents didn’t get a text for hours  Texas Public Radio | TPR
    4. ‘This is a tragedy’ – Texans gather to pay respects to flood victims  BBC
    5. Source: First responders requested emergency alert at least 90 minutes before it was sent  KSAT

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  • How Pharmacists Can Lead the Way in Patient Nutrition and Wellness

    How Pharmacists Can Lead the Way in Patient Nutrition and Wellness

    At McKesson IdeaShare 2025, Lara Zakaria, PharmD, MS, CNS, CDN, IFMCP, delivered a compelling presentation calling for a reimagining of pharmacists’ role in patient nutrition. As the founder of Foodie Farmacist, LLC, and the creator of the concept of pharmaconutrition, Zakaria advocates for a future where pharmacists are recognized as trusted nutrition experts in their communities.1

    Image credit: Chinnapong | stock.adobe.com

    “I want to make this a thing,” she said. “I want this to be the way that we are thought of in our communities, that we are that pharmacy team that makes sure that we talk about nutrition at every opportunity that we can.”1

    Zakaria emphasized how food and nutrition have become moralized, affecting societal perceptions of body size and obesity. She pointed to the limitations of body mass index (BMI) as a health metric, noting it fails to reflect the quality of body composition.1

    “Under-nutrition is just as dangerous as over-nutrition, and that’s something we need to pay attention to,” she said, citing data showing mortality risks at both low and high BMI ranges.2

    Rethinking Diet Quality and the Role of Ultra-Processed Foods

    Ultra-processed foods (UPFs) were another focus of the presentation. Zakaria referenced a narrative review published in Nutrients that found no studies linking UPFs to health benefits but considerable evidence linking them to adverse outcomes such as obesity, cardiovascular disease, and cancer.3 With their heavily altered ingredients, UPFs complicate traditional calorie-based thinking.

    “There’s a whole spectrum of connections between the increase of UPF in our diet and this increased risk, so we can no longer really afford to just look at this as a ‘calories in, calories out’ problem,” she explained. “We have to start thinking about this in a more nuanced way, and we have to start thinking about quality [of food] as well.”

    Zakaria encouraged pharmacists to use patient interactions to “plant some seeds” about nutrition, tying advice to each patient’s broader health goals. For instance, the Mediterranean diet can reduce cardiovascular risk and improve metabolic and inflammatory markers. Drawing from the PREDIMED study, she cited a 30% risk reduction in cardiovascular disease4 and emphasized the role of phytonutrients, polyphenols, and the cultural aspects of food.

    “There’s something to be said about how we eat and how it affects how we view our food, and it might be part of why the Mediterranean diet is so effective.”1

    Addressing Nutrient Depletion, Drug Interactions, and Gut Health

    Zakaria highlighted the importance of macronutrients, micronutrients, and phytonutrients—natural compounds found in foods that influence microbiome function and gene expression. Most people, she noted, are deficient in several key minerals, especially potassium. She also added that there has been an overwhelming number of conflicting headlines about macronutrients, leaving patients confused about whether to consume carbohydrates and fats.1

    Biological and external factors also influence nutritional status. Chronic disease, strenuous physical activity, genetic variations, and environmental exposures all affect nutrient absorption and metabolism. Drug-induced nutrient depletions (DIND), however, are a key concern. Many medications can directly or indirectly impair how the body absorbs or utilizes nutrients. Patients often report symptoms to their physician and start a medication, which eventually leads to different symptoms as a result of depletion. Introducing DIND and nutrition earlier in that conversation can stop this cascade.1

    She also described the stages of nutritional deficiency, noting the importance of early detection before permanent damage occurs. Common drug culprits include proton pump inhibitors, statins, metformin, estrogens, angiotensin-converting enzyme inhibitors, and even caffeine and alcohol.1

    “What we want to do is try to catch those deficiencies as early as possible, before they get to the point where they impair metabolism or cause damage.”1

    Zakaria concluded with some simple food-as-medicine interventions that support gut health and immune function, noting that addressing nutritional issues does not have to be overwhelming for patients. Ingredients like ginger, fennel, turmeric, aloe vera, and epigallocatechin gallate (found in green tea) were highlighted for their anti-inflammatory and digestive benefits and can be easy to incorporate into patients’ diets.1

    With pharmaconutrition, Zakaria hopes to lead a movement that empowers pharmacists to guide patients toward better health, 1 conversation at a time.1

    Starting With the Foundations: Practical Steps for Patient Engagement

    To put pharmaconutrition into practice, Zakaria advised pharmacists to start with foundational strategies. The Mediterranean diet can be an accessible and enjoyable starting point—it’s familiar to many patients, doesn’t require excessive counting or measuring, and is widely supported by evidence.1

    Simple lifestyle modifications can also go a long way. Zakaria recommended encouraging patients to take a 20-minute walk after dinner, incorporate movement throughout the day, and engage in basic exercise. Assessing sleep quality and ruling out sleep apnea is another key step in supporting overall health.1

    Finally, pharmacists should guide patients in reducing alcohol and caffeine consumption and support tobacco cessation. These basic yet powerful changes, she emphasized, can have significant ripple effects on patient outcomes and well-being.1

    REFERENCES
    1. Zakaria L. The Nutrition Games: A Tribute to Nutrient and Medication Collaboration. Presented at: McKesson IdeaShare 2025. Nashville, TN; July 10, 2025.
    2. Visaria A, Setoguchi S. Body mass index and all-cause mortality in a 21st century US population: a national health interview survey analysis. PLoS One. 2023;18(7):e0287218. doi:10.1371/journal.pone.0287218
    3. Elizabeth L, Machado P, Zinöcker M, Baker P, Lawrence M. Ultra-processed foods and health outcomes: a narrative review. Nutrients. 2020;12(7):1955. doi:10.3390/nu12071955
    4. Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med. 2018;378:e34. doi:10.1056/NEJMoa1800389

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  • BGB-16673 Informs Future Direction for BTK Degraders in Relapsed/Refractory CLL/SLL

    BGB-16673 Informs Future Direction for BTK Degraders in Relapsed/Refractory CLL/SLL

    The novel BTK degrader BGB-16673 demonstrated significant antitumor activity and was generally well tolerated without unexpected toxicities for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), according to Lydia Scarfò, MD.

    Data from the phase 1/2 CaDAnCe-101 trial (NCT05006716), presented at the 2025 European Hematology Association Congress, revealed that, at a median follow-up of 15.6 months (range, 0.3-30.6+), patients with relapsed/refractory CLL/SLL (n = 66), experienced any-grade treatment-related adverse effects (TEAEs) at a rate of 95.5%, of which 74.2% were treatment-related and 60.6% were grade 3 or greater.

    Furthermore, patients treated at the 200-mg dose level of BGB-16673 achieved an overall response rate (ORR) of 93.8%, including 1 complete response, 12 partial responses, and 2 partial responses with lymphocytosis. The 12-month progression-free survival (PFS) rate was 77.4%. (95% CI, 63.1%-86.8%).

    “We have made great progress in the past few years in the treatment of patients with CLL, but the disease remains incurable in the majority of patients, so we need to increase the therapeutic options available, and BTK degraders look very promising,” Scarfò said during an interview with OncLive® at the meeting.

    In the interview, Scarfò discussed the rationale for CaDAnCe-101, the mechanism of action of BGB-16673, safety and efficacy data from the study, and future directions for the novel BTK degrader.

    Scarfò is a physician scientist at the B-Cell Neoplasia Unit and an assistant professor at the Università Vita-Salute Raffaele in Milano, Italy.

    OncLive: What was the rationale for CaDAnCe-101?

    Scarfò: The treatment of patients with CLL has radically changed in the last few years, thanks to the introduction of BCL2 and BTK inhibitors. The issue is that patients exposed to BTK and BCL2 inhibitors still have a chance of relapse, and they become a very difficult-to-treat population, so we need drugs that act with a different mechanism of action to overcome resistance and achieve long-term disease control.

    What is the mechanism of action of BGB-16673?

    BGB-16673 is a BTK degrader, meaning that the target is BTK, which is crucial for the survival and proliferation of CLL cells. However, instead of inhibiting the enzymatic activity of BTK, BGB-16673 targets BTK for degradation via the proteasome pathway.

    What were the key design characteristics of CaDAnCe-101?

    The phase 1 study is a basket trial [that included] patients with different B-cell malignancies and were enrolled into the trial we recently presented. [At the EHA Congress,] we have presented the results of the use of BGB-16673 in patients with relapsed/refractory CLL, both in the dose escalation and in the dose expansion phase of the trial.

    What were the updated safety findings presented at EHA?

    The reassuring thing is that we can confirm that BGB-16673 is generally well tolerated, with no unexpected toxicities associated with the use of this drug because the target is BTK. We do expect some cardiovascular adverse effects and some bleeding events, but they were very limited in the patient cohort. We also have to take into consideration that the follow-up remains pretty short.

    What were the key efficacy data?

    We have evaluated the ORR in the whole patient population, and we are happy to confirm that BGB-16673 is effective in the majority of patients, and in particular, at the recommended dose for the expansion phase of 200 mg daily, the ORR is 93.8% and we now have longer follow-up. Therefore, we can confirm that in terms of PFS, the response is endurable with a 12-month PFS rate of 77.4%.

    What are the next steps for this research?

    Thanks to the results of this phase 1/2 trial, several trials are currently ongoing trying to compare BGB-16673 with the standard of care. Several phase 2 and phase 3 trials are currently being performed to understand how to add this [therapy] to our therapeutic armamentarium in [clinical practice].

    We hope that with additional evidence, we can confirm the efficacy and the safety of these mechanisms of action, of the specific compound, but also in general, of the use of a BTK degrader as a potential mechanism of action. In the near future, we hope we can add these mechanisms of action to our therapeutic armamentarium.

    Reference

    Scarfò L, Parrondo RD, Thompson MC, et al. Updated efficacy and safety of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients (pts) with relapsed or refractory (R/R) CLL/SLL: results from the ongoing phase (ph) 1 CADANCE-101 study. Presented at: 2025 European Hematology Association Congress; June 12-15, 2025; Milan, Italy. Abstract S158.

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  • UK Study: 3D Heart Modeling Reveals Breakthrough in ECG Interpretation

    UK Study: 3D Heart Modeling Reveals Breakthrough in ECG Interpretation

    July 10, 2025 — A study led by scientists at King’s College London has revealed how the physical orientation of the heart inside the chest dramatically influences the electrical signals captured in an electrocardiogram (ECG) — a discovery that could pave the way for more personalized and accurate heart diagnostics. 

    With data from more than 39,000 participants from the UK Biobank, this is one of the largest population-based studies to date exploring the relationship between heart anatomy and electrical activity. By combining 3D heart imaging with ECG data, the team created simplified digital twins of each participant’s heart. These personalized models allowed researchers to explore how the heart’s anatomical position, known as the anatomical axis, aligns with a spatial metric of electrical activity, or electrical axis.  

    Digital twins are emerging as a powerful tool in cardiovascular research, enabling scientists to simulate and study the heart’s structure and function in unprecedented detail. In this study, they were key to revealing how natural variations in heart orientation, shaped by factors such as body mass index (BMI), sex, and hypertension, can significantly influence ECG readings. 

    The researchers proposed new, standardized definitions for both anatomical and electrical axes based on their alignment in 3D space. They found that people with higher BMI or high blood pressure tend to have hearts that sit more horizontally in the chest, and that this shift is mirrored in their ECG signals. The study also revealed clear differences between men and women: male hearts were generally more horizontally oriented than female hearts, a structural difference that was reflected in their surface electrical activity. These sex-based variations highlight the need for more tailored approaches to ECG interpretation. 

    By identifying and quantifying this variability across a large population, the study highlights the importance of distinguishing between normal anatomical differences and early signs of disease. This could help clinicians detect conditions such as hypertension, conduction abnormalities, or early heart muscle changes sooner and more precisely – especially in patients whose heart orientation deviates from standard assumptions. 

    The findings point to a future where ECGs are no longer interpreted using a one-size-fits-all approach, but instead tailored to each patient’s unique anatomy. This personalized perspective could reduce misdiagnoses and support earlier, more targeted interventions. 

    Mohammad Kayyali, lead author and PhD student at the King’s School of Biomedical Engineering & Imaging Sciences, said: “Large-scale biomedical resources like the UK Biobank are paving the way for patient-centric disease characterization by enabling detailed analysis of anatomical and electrophysiological variability across the population. This work demonstrated differences in cardiac axes among healthy and diseased individuals, highlighting the potential to enhance digital twin personalization and improve disease prediction and characterization, ultimately supporting more tailored clinical care.” 

    Professor Pablo Lamata, report author and professor of biomedical engineering at King’s, said: “The ability to build personalized models (i.e. digital twins) of the cardiovascular system is an exciting research area, where we hope to find new parameters that can better inform about prevention, diagnosis and risks of cardiovascular diseases. In this work, we start to explore these uncharted waters, and we hope we will soon propose new ways to early detect conditions such as electrical conduction disorders.”


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  • Randomized Trial Highlights Uncertainties of Ambroxol to Improve Cognition in Parkinson Disease Dementia

    Randomized Trial Highlights Uncertainties of Ambroxol to Improve Cognition in Parkinson Disease Dementia

    Stephen H. Pasternak, MD, PhD

    Results from a recently published, 52-week, phase 2, double-blind, placebo-controlled study showed that ambroxol, a chaperone for β-glucocerebrosidase, was safe in patients with Parkinson disease dementia (PDD); however, its effects on cognition were not confirmed. Positive data revealed stabilization of neuropsychiatric symptoms and plasma glial fibrillary acidic protein (GFAP) levels, a marker of neurodegeneration.1

    After excluding the low-dose group due to recruitment challenges, the study featured a cohort of patients with PDD who were randomly assigned 1:1 to either high-dose ambroxol at 1050 mg (n = 22) or placebo (n = 24) for a 52-week period, with an additional 26-week open-label extension. All told, change in Alzheimer Disease Assessment Scale–cognitive subscale 13 (ADAS-Cog13) and Clinician Global Impression of Change (CGIC), the study’s primary outcomes, were not different between the groups at week 26 or week 52.

    In the study, investigators observed no statistical between-group differences on secondary outcomes as well, which included Clinical Dementia Rating Scale, Parkinson’s Disease Cognitive Rating Scale, Trail Making Test, and Stroop test, among many others. The study authors did observe a trend in total Neuropsychiatry Inventory (NPI) score (t = –1.86; P = .07), where the placebo group worsened from baseline to week 52 while those in the ambroxol group remained stable. NPI score among GBA1 carriers revealed that 2 patients taking placebo changed by 0 and +10 points, whereas patients taking high-dose ambroxol showed score reductions of –1, –8, –12, and –15 points at week 52.

    Led by senior author Stephen H. Pasternak, MD, PhD, the study aimed at testing the safety and tolerability of ambroxol, as well as its effects in slowing the progression of cognitive deficits in PDD. Ambroxol, an over-the-counter expectorant with documented safety profile, has been identified as a high throughput screen as a pharmacological chaperone of GCase and an inhibitor that binds and increases levels of GCase, while dissociating from GCase in the acidic environment of the lysosome. Prior to this study, ambroxol has shown an ability to increase GCase and reduce alpha-synuclein in mice and nonhuman primate brains.

    Ambroxol was shown to be safe in patients with PDD, as those on the drug had a similar rate of adverse events (AEs) than those in the placebo group. Overall, 8 patients on ambroxol (2 low-dose; 6 high-dose) and 3 patients taking placebo (12.5%) withdrew because of AEs. There were 7 hospitalizations, considered a serious AE, found in the ambroxol group. These included one patient on low-dose admitted twice for delirium, and other participants admitted to urinary tract infection (low-dose), worsening hallucinations and recurrent falls (high dose), infection after elective surgery (low dose), rigidity and worsening hallucinations (high dose), and severe leg weakness (high dose).

    READ MORE: FDA Approves Updated Label for Alzheimer Therapy Donanemab to Lower ARIA-E Risk

    For gastrointestinal disorders, 12% of ambroxol-patients reported these vs 5% of those taking placebo. In addition, there were more psychiatric AEs in the placebo group (23%) compared with the ambroxol group (16.6%), as well as more injuries/falls (29.7% vs 22.8%).

    The plasma biomarker analysis comprised 15 patients on high dose ambroxol and 20 on placebo, all who had baseline and week 52 samples. When excluding those who had a clinically significant AE or were not taking treatment within 1 month of the end of trial (6 taking ambroxol and 3 taking placebo excluded), the placebo group demonstrated an increase in GFAP from baseline over the 52 weeks (mean: 135.07 pg/mL to 167.90 pg/mL) whereas those on ambroxol high dose did not (mean: 127.95 pg/mL to 118.05 pg/mL).

    At week 26, GCase levels were significantly higher in the ambroxol group vs placebo (12.45 ± 1.97 vs 8.50 ± 1.96 nmol/h/mg; 91% CI, 11.54–13.36 vs 7.65–9.34; P = .05), and remained elevated but not statistically different at week 52 (11.45 ± 1.59 vs 8.59 ± 1.56 nmol/h/mg; 95% CI, 10.61–12.28 vs 7.86–9.31). Considerable inter-patient variability was observed, including at baseline.

    “In conclusion, results of this randomized clinical trial reveal that ambroxol was deemed safe and well tolerated in PDD. Sufficient drug levels were achieved, and target engagement was demonstrated based on increased white blood cell GCase activity levels,” Pasternak et al wrote. “Future studies should attempt to reduce the heterogeneity in study population, focus on recruiting more GBA1 carriers, and assess GFAP as a potential biomarker to be used in PD clinical trials.”

    REFERENCE
    1. Silveira CRA, Coleman KKL, Borron K, et al. Ambroxol as a treatment for Parkinson disease dementia: a randomized clinical trial. JAMA Neurol. Published online June 30, 2025. doi:10.1001/jamaneurol.2025.1687

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  • No Long-Term Dementia Risk Linked to Transient Ischemic Attack, 20-Year Study Finds

    No Long-Term Dementia Risk Linked to Transient Ischemic Attack, 20-Year Study Finds

    Vasileios‐Arsenios Lioutas, MD

    Credit: Beth Israel Deaconess Medical Center

    A recent study found no significant difference in dementia incidence over a 20-year follow-up among individuals who had or did not have a transient ischemic attack.1

    “Our findings challenge our initial hypothesis and diverge from certain existing literature studies that have proposed persistent cognitive decline following [transient ischemic attack],” wrote investigators, led by Vasileios‐Arsenios Lioutas, MD, from the department of neurology at Beth Israel Deaconess Medical Center, Harvard Medical School. “It is noteworthy, however, that other studies suggest cognitive impairment after [transient ischemic attack] is a transient phenomenon, potentially part of an acute confusional state or delirium.”

    According to the Cleveland Clinic, multi-infarct dementia results from a series of small strokes—transient ischemic attacks.2 Transient ischemic attacks and strokes share symptoms, but the former may be milder. Risk factors for multi-infarct dementia include hypertension, diabetes, conditions that can cause blood clots (atherosclerosis, coronary heart disease, heart valve disease, and carotid artery disease), hyperlipidemia, and smoking.

    Despite existing data, the link between transient ischemic attack and dementia is still under-characterized. Investigators aimed to determine the long-term incidence of dementia following a transient ischemic attack and whether the attack prompts changes in vascular risk factors. The primary outcome was the 20-year incidence of all-cause dementia.

    The team recruited participants from a nested, matched, longitudinal cohort study within the community-based Framingham Heart Study. Participants without dementia or transient ischemic attack (n = 1485) were matched 5:1 by age and sex to 297 participants with first incident transient ischemic attack at > 60 years. The arm with incident transient ischemic attack had a sample of 47% men and a mean age of 72.7 ±7.7 years. Participants with transient ischemic attack were more likely to have hypertension (78% vs 67%; P = .0006), coronary heart disease (37% vs 7%; P = .018), and atrial fibrillation (11% vs 7%; P = .018).

    Over a follow-up of 8.9 years, 19% and 24% of patients with and without transient ischemic attack, respectively, developed dementia (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.71 – 1.24; P = .063). The association remained after adjusting for strokes and the competing risk of death. Once the team removed case-control sets with interim stroke, 25% and 24% of participants with and without transient ischemic attack, respectively, developed dementia (HR, 1.17; 95% CI, 0.78 – 1.73; P = .448).

    “It is still unclear whether this represents a true lack of association between [transient ischemic attack] and cognitive decline or a true but relatively small risk exists but can be mitigated by early initiation and consistent adherence with secondary prevention,” the team wrote.

    The analysis showed that participants with transient ischemic attack were more likely to have a reduction in the frequency of smoking (18% to 11%; P = .025), an increase in anticoagulant use (3% to 18%; P = .0005), and a slight increase in aspirin use (46% to 61%; P = .052).

    Furthermore, participants who started anticoagulation after transient ischemic attack had a greater likelihood of developing dementia (HR, 4.71; 95% CI, 1.89 – 11.71; P < .001). This was observed after adjusting for atrial fibrillation (HR, 4.01; 95% CI, 1.57–10.20; P = .0005).

    No participants in either arm experienced changes in their mean SBP or had high systolic SBP (SBP > 149 mm Hg).

    “Prospective studies with well‐matched controls, active cognitive surveillance, and sufficiently long follow‐up are necessary to better characterize the cognitive repercussions of [transient ischemic attack] and the impact of secondary stroke prevention in cognitive health,” investigators wrote.

    References

    1. Lioutas VA, Peloso G, Romero JR, et al. Long-Term Incidence of Dementia Following Transient Ischemic Attack: A Longitudinal Cohort Study. J Am Heart Assoc. Published online July 3, 2025. doi:10.1161/JAHA.124.037817
    2. Multi-Infarct Dementia. Cleveland Clinic. July 10, 2025. https://my.clevelandclinic.org/health/diseases/6063-multi-infarct-dementia. Accessed July 10, 2025

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