Breast cancer remains a formidable challenge in oncology, with many subtypes exhibiting complexity that thwarts standard treatments. Over the past decade, CDK4/6 inhibitors have emerged as a cornerstone in managing hormone receptor-positive breast cancer, significantly improving patient outcomes. However, resistance to these inhibitors frequently develops, diminishing their effectiveness and leaving clinicians with limited alternatives. This pressing issue has motivated scientists to explore additional molecular targets within the cell cycle machinery to overcome resistance and extend patient survival.

Central to cell proliferation are cyclin-dependent kinases (CDKs), enzymes that regulate progression through different phases of the cell cycle by phosphorylating key substrates. CDK4 and CDK6, when activated, facilitate the transition from the G1 to S phase, promoting DNA replication and cell division. Inhibition of these kinases arrests the cycle, suppressing tumor growth. Yet, cancer cells often bypass CDK4/6 inhibition by upregulating CDK2 activity, another pivotal kinase in the G1 to S phase transition. This compensatory mechanism contributes heavily to resistance, making CDK2 an attractive candidate for targeted inhibition.

The research team’s investigation into BLU-222, a next-generation CDK2 inhibitor, involved comprehensive in vitro and in vivo analyses. Employing breast cancer models resistant to CDK4/6 inhibitors, they discovered that BLU-222 effectively suppressed CDK2 activity, significantly reducing tumor cell proliferation. Intriguingly, when combined with existing CDK4/6 inhibitors, BLU-222 exerted a synergistic effect, enhancing anti-cancer efficacy beyond what each could achieve alone. This synergism underscores a promising therapeutic avenue for patients whose tumors have adapted to evade monotherapy.

Delving deep into the molecular biology of this response, the study elucidated the role of cyclin-dependent kinase inhibitors p21 (CDKN1A) and p27 (CDKN1B). These proteins act as natural brakes on CDK activity, enforcing checkpoints that halt cell cycle progression in response to DNA damage or oncogenic stress. BLU-222 treatment was shown to induce upregulation of both p21 and p27, amplifying their inhibitory effects on CDKs and consequently reinforcing cell cycle arrest. This induction mechanism appeared critical for the heightened therapeutic impact observed with the BLU-222 and CDK4/6 inhibitor combination.

Mechanistically, the interplay between p21, p27, and CDKs can be viewed as a tightly controlled network, where the balance between kinase activity and inhibitor levels dictates cellular fate. By boosting p21 and p27, BLU-222 not only suppresses CDK2 but also indirectly influences CDK4/6 function, effectively dampening the cell cycle advance at multiple nodes. Such a multipronged blockade could explain the overcoming of resistance phenotypes that typically arise through adaptive rewiring of cancer signaling pathways.

Furthermore, the study utilized sophisticated genomic and proteomic profiling techniques to characterize changes within tumor cells following treatment. These analyses revealed shifts in expression patterns consistent with cell cycle exit and senescence, as well as enhanced apoptosis markers, suggesting that the combination therapy promotes not only growth arrest but also programmed cell death. This dual effect increases the likelihood of durable responses, an essential feature for tackling aggressive and recurrent breast cancer cases.

Animal models bearing patient-derived xenografts of resistant breast tumors validated the translational potential of this therapeutic strategy. Mice receiving the BLU-222 and CDK4/6 inhibitor combo exhibited significant tumor regression compared to controls or single-agent treatments. Importantly, the toxicity profile remained manageable, indicating that the regimen could be feasible for clinical application without undue adverse effects, a critical consideration in cancer therapy development.

The implications of these findings extend beyond breast cancer, as aberrant CDK activity is a hallmark of numerous malignancies. By establishing a framework for dual CDK targeting augmented by endogenous inhibitor induction, this work opens avenues for broad-spectrum oncology approaches. It also invites further exploration into combinations with other targeted therapies or immunomodulatory agents, potentially enhancing efficacy through complementary mechanisms.

From a clinical standpoint, these insights advocate the re-evaluation of treatment algorithms for breast cancer patients exhibiting resistance to standard CDK4/6 inhibitors. Incorporating BLU-222 or related CDK2 inhibitors into therapeutic regimens might offer a new lifeline, especially for those with limited options. Future clinical trials inspired by this research will be critical to confirm safety, dosing parameters, and real-world efficacy, paving the path for regulatory approvals and routine clinical use.

Moreover, the study underscores the importance of precision medicine, emphasizing that understanding specific molecular adaptations within tumors is key to counteracting resistance. By tailoring interventions that target multiple components of the cell cycle machinery, oncologists can devise more robust treatments that anticipate and thwart cancer’s attempts to survive and proliferate.

The discovery also prompts a reconsideration of the tumor microenvironment’s role in moderating response to CDK inhibitors. While the current work focused primarily on tumor-intrinsic mechanisms, the influence of stromal cells, immune populations, and extracellular matrix components on drug sensitivity remains an exciting frontier. Integrating these dimensions may further refine therapeutic strategies and enhance patient outcomes.

In sum, Luo, Wang, Bui, and their colleagues’ investigation represents a significant leap forward in breast cancer therapeutics. By illustrating the synergy of BLU-222 with existing CDK4/6 inhibitors and unraveling the critical role of p21 and p27 induction in overcoming drug resistance, they offer a blueprint for next-generation treatments that could dramatically improve survival and quality of life for many patients battling this formidable disease.

As the oncology community eagerly anticipates subsequent clinical validation, this study will undoubtedly inspire renewed efforts in drug development targeting the cell cycle, heralding a new era in the fight against resistant breast cancer. The integration of innovative small molecules like BLU-222 into combination schemes exemplifies the power of rational drug design grounded in molecular biology, promising to transform outcomes for patients worldwide.

This research also serves as a testament to the relentless pursuit of scientific innovation needed to outpace cancer’s adaptive capacity. It reminds us that by decoding the intricate dance of cellular regulators such as CDKs, p21, and p27, we inch closer to unraveling cancer’s vulnerabilities and crafting therapies that are both potent and precise.

Subject of Research: CDK2 inhibition combined with CDK4/6 inhibitors to overcome drug resistance in breast cancer through the induction of cell cycle inhibitors p21 and p27.

Article Title: CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction.

Article References:
Luo, L., Wang, Y., Bui, T. et al. CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction. Nat Commun 17, 619 (2026). https://doi.org/10.1038/s41467-025-67865-4

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41467-025-67865-4

Central to this research is the KRAS gene, a critical component in the regulation of cell proliferation and survival. Under normal physiological conditions, RAS proteins cycle between active and inactive forms, effectively acting as molecular switches that govern cell division. However, mutations in the KRAS gene, particularly the G12C variant, lock the protein in an active conducting state, incessantly signaling cells to multiply, thereby fueling cancer growth. This mutation is unfortunately prevalent in NSCLC, present in approximately 10-14% of cases, and is known for driving tumor progression and therapeutic resistance.

The first study within this publication reveals a sophisticated escape mechanism employed by cancer cells treated with KRAS G12C inhibitors. Despite initial therapeutic effectiveness, tumors rapidly reactivate RAS signaling pathways to circumvent inhibition, fostering resistance and disease progression. Importantly, the research introduces next-generation RAS(ON) inhibitors, exemplified by the compound RMC-7977, capable of targeting not only the mutant KRAS but also the wild-type RAS proteins. This dual-targeting approach effectively blocks multiple resistance pathways, thereby reinstating control over tumor growth and offering a robust strategy against adaptive resistance.

Parallel to these findings, the second study explores vulnerabilities in the cellular machinery that cancer cells develop as they adapt to KRAS inhibition. Researchers identified that resistance correlates with heightened dependency on CDK12 and CDK13, cyclin-dependent kinases critical for mediating DNA damage repair and mitotic control. By selectively inhibiting CDK12/13, the team induced mitotic arrest—effectively halting cell division—which culminated in the selective elimination of resistant cancer cells. This intervention exploits the tumor’s acquired reliance on DNA repair pathways to survive, turning a resistance mechanism into a therapeutic target.

Crucially, combining KRAS G12C inhibitors with CDK12/13 inhibitors produced a synergistic effect that delayed or entirely prevented the emergence of resistant cancer cell populations in both in vitro and in vivo models. This co-treatment strategy not only prolonged the duration of treatment efficacy but also circumvented more complex resistance mechanisms, such as those independent of RAS signaling and related to epithelial-mesenchymal transition (EMT), a phenotypic change often associated with increased metastatic potential.

This dual-pronged therapeutic approach addresses one of the central challenges in targeted cancer treatments: the inevitability of resistance. The durability of KRAS G12C inhibitors has been limited by rapid tumor adaptation via genetic and non-genetic routes. By innovatively targeting the active state of RAS proteins through RAS(ON) inhibitors and exploiting the enhanced dependence on DNA repair mechanisms with CDK12/13 blockade, these studies propose a coherent framework to not only delay resistance but also mechanistically dismantle the cancer cell’s survival strategies.

Mechanistically, RAS(ON) inhibitors differ fundamentally from earlier KRAS G12C inhibitors, which primarily target the inactive GDP-bound state of the protein. Targeting the active GTP-bound form allows RAS(ON) inhibitors to simultaneously inhibit both mutant and wild-type RAS isoforms, which tumor cells often co-opt to evade therapy. This wider blockade of RAS signaling pathways eliminates alternate routes tumors exploit, thereby tightening the therapeutic lock on tumor proliferation.

Entry of CDK12/13 inhibitors into this therapeutic schema is equally strategic. CDK12 and CDK13 orchestrate transcriptional elongation of genes involved in DNA repair and cell cycle progression. Tumors resistant to KRAS inhibition become increasingly reliant on these kinases to manage genomic integrity and navigate mitosis successfully. Pharmacologic inhibition of CDK12/13 disrupts these essential processes, inducing catastrophic mitotic arrest and promoting tumor cell death specifically in resistant cell populations.

The clinical implications of these findings are profound. By mapping the molecular underpinnings of resistance in unprecedented detail, the research lays the groundwork for future clinical trials that can implement combination treatments, precisely timed and tailored to prevent or counteract resistance. Such an approach promises to enhance therapeutic durability, improve progression-free survival, and ultimately transform the prognosis for patients harboring KRAS G12C mutations.

These studies underscore the importance of a multifaceted assault on cancer cells, addressing both the primary oncogenic drivers and the secondary adaptations that enable tumor persistence. The research also illustrates the power of translational science, where detailed molecular insights are rapidly integrated into rational therapeutic design, setting the stage for innovative clinical interventions that could shift the current paradigms of lung cancer management.

Moreover, the adoption of RAS(ON) inhibitors widens the potential of targeted therapies beyond KRAS G12C to possibly include other RAS-driven malignancies, given the central role of RAS signaling in numerous cancers. Similarly, CDK12/13 inhibitors hold promise as part of a larger arsenal aimed at disrupting DNA repair and cell cycle pathways exploited by resistant tumors, suggesting broader applications across cancer types.

In summary, the pioneering research conducted at Moffitt Cancer Center delivers a compelling strategy to confront one of the most pressing obstacles in cancer therapeutics: resistance. By simultaneously targeting the reactivation of RAS signaling and the compensatory dependence on DNA repair through CDK12/13 inhibition, these studies offer hope for more durable and effective treatments for the many patients battling KRAS G12C-mutant non-small cell lung cancer.

Such transformative insights are supported by robust experimental models and herald a new chapter in precision oncology, where an intimate understanding of tumor biology informs the design of next-generation combination therapies. As these findings progress toward clinical validation, they may soon redefine standards of care, providing a beacon of hope in the fight against one of the deadliest forms of cancer.

Subject of Research: Cells

Article Title: Targeting CDK12/13 Drives Mitotic Arrest to Overcome Resistance to KRASG12C Inhibitors

News Publication Date: 30-Oct-2025

Web References:

• https://aacrjournals.org/cancerres/article-abstract/doi/10.1158/0008-5472.CAN-25-0450/766922/Targeting-CDK12-13-Drives-Mitotic-Arrest-to?redirectedFrom=fulltext
• https://aacrjournals.org/cancerres/article-abstract/doi/10.1158/0008-5472.CAN-25-0600/766923/RAS-GTP-Inhibition-Overcomes-Acquired-Resistance?redirectedFrom=fulltext

References:
Supported by the National Cancer Institute (5R01CA262530-0, P30-CA076292) and State of Florida Bankhead Coley Grant (5BC07).

Keywords: Lung cancer, KRAS G12C mutation, drug resistance, RAS(ON) inhibitors, CDK12/13 inhibition, mitotic arrest, targeted cancer therapy, non-small cell lung cancer, therapeutic resistance mechanisms

Cisplatin remains one of the frontline chemotherapeutic agents against various malignancies, including cervical cancer. Despite its efficacy, resistance to cisplatin poses a formidable challenge, often leading to treatment failure and poor clinical outcomes. The molecular pathways contributing to this resistance are complex and multifaceted, invoking diverse survival mechanisms within cancer cells. The recent investigation sheds light on how SLC25A10 mediates these responses through interaction with ferroptotic pathways.

Ferroptosis, an iron-dependent process characterized by the accumulation of lethal lipid peroxides, acts as a natural barrier against tumor progression and a targetable vulnerability in cancer therapy. Unlike apoptosis or necrosis, ferroptosis operates through distinct metabolic and oxidative stress axes, thereby representing a critical mechanism by which cancer cells may succumb when subjected to therapeutic interventions. The study highlights the inhibitory effect of SLC25A10 on ferroptosis, thereby facilitating cellular survival in the cytotoxic milieu induced by cisplatin.

Delving into the molecular intricacies, the researchers identified that SLC25A10 functions as a mitochondrial dicarboxylate carrier, orchestrating redox homeostasis within the organelle. By regulating the transport of metabolites crucial for maintaining glutathione levels—the primary intracellular antioxidant—SLC25A10 exerts control over the oxidative stress response. Consequently, the suppression of ferroptotic lipid peroxidation under the influence of SLC25A10 elevates cancer cell resilience against cisplatin-induced cytotoxicity.

The methodology employed was both rigorous and multi-dimensional, combining gene expression analyses, in vitro functional assays, and in vivo tumor models. Knockdown experiments targeting SLC25A10 potentiated ferroptosis markers while enhancing the cytotoxic efficacy of cisplatin. Conversely, overexpression of SLC25A10 curtailed lipid peroxidation and diminished ferroptotic cell death, thereby corroborating its functional role in drug resistance mechanisms.

Intriguingly, the metabolic profiling of cervical cancer cells revealed that SLC25A10 modulates cellular bioenergetics and redox status through its transport activity. This modulation preserves mitochondrial integrity and prevents excessive reactive oxygen species (ROS) accumulation, which would otherwise trigger ferroptosis. The findings suggest that SLC25A10 acts as a safeguard against oxidative stress-induced demise, thereby underpinning a novel survival axis within cisplatin-resistant cervical cancer cells.

Beyond the intrinsic cellular mechanisms, the study touches upon the clinical implications of SLC25A10 expression levels. Analysis of patient-derived tumor samples demonstrated a positive correlation between elevated SLC25A10 expression and poor response to cisplatin-based therapies. This association positions SLC25A10 as a potential prognostic biomarker to stratify patients according to their predicted chemotherapeutic outcomes and tailor personalized treatment regimens.

Moreover, the therapeutic potential of targeting SLC25A10 was explored through pharmacological inhibition and gene silencing approaches. These interventions sensitized resistant cervical cancer cells to cisplatin, restoring ferroptosis susceptibility and enhancing tumor suppression in preclinical models. Such findings highlight the translational promise of combining ferroptosis-inducing agents with existing chemotherapy to overcome resistance barriers in clinical settings.

The study also contextualizes its findings within the broader landscape of cancer metabolism and cell death regulation. It emphasizes that metabolic rewiring, especially in mitochondrial functions, is integral to the adaptive responses of tumors facing chemotherapeutic stress. By pinpointing SLC25A10’s central role, the research enriches our comprehension of how organelle-specific metabolite transporters can influence cancer survival pathways.

In terms of future directions, the authors advocate for the development of selective SLC25A10 inhibitors to evaluate their efficacy and safety in clinical trials. Additionally, they propose investigating combinatorial regimens that synergize cisplatin with ferroptosis inducers to maximize antitumor efficacy. The research also calls for deeper exploration of SLC25A10’s role in other cancer types where cisplatin resistance remains a critical hurdle.

This study thus represents a paradigm shift in the quest to surmount chemotherapy resistance. It paves the way for a new class of therapeutic interventions that exploit the vulnerabilities within the ferroptosis regulatory network. By deciphering how mitochondrial metabolite transport modulates cell death pathways, the findings equip oncologists and researchers with novel targets to potentially improve outcomes for cervical cancer patients.

Notably, the elucidation of SLC25A10’s ferroptosis-inhibiting function also adds a layer of complexity to our understanding of mitochondrial dynamics in cancer. It challenges researchers to reexamine mitochondria not merely as powerhouses but as pivotal modulators of cell fate decisions under therapeutic pressures. This nuanced perspective could inspire innovative designs for mitochondria-targeted therapies beyond the context of cervical cancer.

Furthermore, the implications of this research transcend oncology, as ferroptosis has been implicated in various pathological states, including neurodegeneration and ischemic injury. Insights into SLC25A10’s function could thus have interdisciplinary relevance, catalyzing advancements across biomedical fields where oxidative stress and regulated cell death are critical.

In conclusion, the identification of SLC25A10 as a key regulator of cisplatin resistance through ferroptosis inhibition heralds a significant breakthrough in cancer biology. These findings underscore the importance of targeting mitochondrial metabolism and redox balance to overcome drug resistance and enhance therapeutic efficacy. As this research progresses from bench to bedside, it holds promise for transforming cervical cancer treatment paradigms and improving survival rates worldwide.

Subject of Research:
Article Title:
Article References:
Ma, C., Lu, X., Ni, C. et al. SLC25A10 promotes cisplatin resistance by inhibiting ferroptosis in cervical cancer. Cell Death Discov. 11, 447 (2025). https://doi.org/10.1038/s41420-025-02712-5
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s41420-025-02712-5
Keywords: cisplatin resistance, cervical cancer, SLC25A10, ferroptosis, mitochondrial metabolism, oxidative stress, chemotherapy resistance, lipid peroxidation, glutathione, reactive oxygen species, tumor survival, cell death regulation

The investigation spearheaded by Huang’s team employs both in vivo models and in vitro cellular systems to unravel how the GAD1/GABA axis contributes to the diminished therapeutic response observed with anlotinib. Their comprehensive analysis suggests that elevated GABA biosynthesis within hepatoblastoma cells fosters an intrinsic shield against the drug’s cytotoxic effects, thereby enabling tumor survival and growth despite treatment. This discovery not only widens the understanding of resistance mechanisms to tyrosine kinase inhibitors but also positions the GABAergic system as a novel target for overcoming drug resistance in liver cancers.

The pertinence of this study is underscored by the increasing clinical use of anlotinib, which inhibits multiple receptor tyrosine kinases involved in angiogenesis and tumor proliferation, including VEGFR, PDGFR, and FGFR families. While anlotinib has demonstrated remarkable antitumor activity across various malignancies, intrinsic resistance seen in hepatoblastoma challenges its therapeutic promise. Prior to this research, explanations for anlotinib resistance largely centered around genetic mutations and alternative signaling pathways, but the direct involvement of neurotransmitter pathways, specifically the GABAergic system, was uncharted territory.

Intriguingly, GABA is traditionally recognized as the primary inhibitory neurotransmitter in the central nervous system, regulating neuronal excitability and plasticity. However, emerging evidence reveals that GABA and its synthetic enzymes have extraneural functions, including cell proliferation, migration, and apoptosis modulations across diverse tissues. By exploring this paradigm shift, Huang et al. integrate neurobiology with oncology, unveiling how hepatoblastoma cells may co-opt the GABA signaling machinery to augment survival under therapeutic stress.

Through meticulous in vitro experiments, the researchers observed that hepatoblastoma cell lines with higher GAD1 expression—and consequently increased intracellular GABA synthesis—exhibited pronounced resistance to anlotinib-induced apoptosis. Contrarily, silencing GAD1 via RNA interference sensitized these cells to the drug, reducing viability and inducing caspase-dependent cell death pathways. These findings highlight GAD1 as a critical molecular node controlling drug responsiveness, suggesting that GABA synthesis acts as a cellular safeguard negating anlotinib’s antitumor activity.

The in vivo arm of the study reinforces these data, where xenograft models with upregulated GAD1 maintained robust tumor growth despite anlotinib administration, compared to controls. Furthermore, pharmacological inhibition of GABA synthesis synergized with anlotinib, dramatically suppressing tumor progression and enhancing survival rates in treated animals. This preclinical evidence strongly advocates for combined therapeutic strategies targeting both tyrosine kinase and GABA pathways to circumvent intrinsic resistance.

Delving into molecular mechanisms, the team dissected downstream effectors of GABA signaling, uncovering that GABA production modulates intracellular signaling cascades linked to cell survival and metabolism. Specifically, GABA appears to activate pathways that confer metabolic adaptation and oxidative stress resistance, thereby fortifying hepatoblastoma cells against anlotinib-induced cytotoxic insults. These metabolic rewiring events also resonate with the current understanding of cancer cell plasticity, where tumors exploit metabolic versatility to thrive under therapeutic pressure.

This study also raises compelling questions about the interplay between neuronal signaling molecules and cancer biology. The identification of GABA as a contributor to intrinsic drug resistance in hepatoblastoma encourages broader investigations into neurotransmitter pathways in oncogenesis and therapy resistance across other malignancies. Such cross-disciplinary research could unveil unanticipated drug targets, revolutionizing treatment paradigms.

Moreover, targeting GABA synthesis or signaling offers a tantalizing adjunctive avenue to potentiate existing antitumor agents. Pharmacological inhibitors of GAD1 or GABA receptors, already under exploration in neurological disorders, might be repurposed and optimized for oncology applications. This strategy promises a dual assault on tumor viability by disrupting critical survival signals and compromising the tumor microenvironment’s protective niche.

Importantly, the translational potential of Huang et al.’s findings is significant. Hepatoblastoma, predominantly affecting pediatric populations, demands treatments with high efficacy yet minimized toxicity. Incorporating GABA pathway modulators could enhance the potency of anlotinib at lower doses, potentially reducing adverse effects and improving patient quality of life. It also opens the door for personalized medicine approaches, where GAD1 expression levels might serve as biomarkers to stratify patients likely to benefit from combination therapies.

The researchers acknowledge certain limitations, including the need for validation of their findings across a wider array of hepatoblastoma subtypes and in clinical trial settings. Additionally, the safety profile of combining anlotinib with GABA pathway inhibitors requires thorough evaluation, considering potential neurological side effects. Nevertheless, the robust experimental evidence forms a compelling rationale for advancing to translational applications.

In light of these revelations, future research avenues appear rich with promise. Exploring the extent to which other neurotransmitter systems participate in drug resistance, dissecting the precise molecular intermediaries linking GABA signaling to oncogenic pathways, and developing selective inhibitors tailored for oncological use are all imperative next steps. These endeavors could collectively dismantle the intrinsic resistance fortress that currently shields hepatoblastoma from optimal therapeutic eradication.

To summarize, Huang and colleagues’ illuminating research reveals that the GAD1/GABA metabolic axis is a crucial mediator of anlotinib intrinsic resistance in hepatoblastoma, providing a novel conceptual framework for tackling therapeutic failure. This interdisciplinary approach harmonizes neurochemical insights with cancer pharmacology, spotlighting the intricate biological networks tumors exploit to outwit medical interventions. Their work not only propels the understanding of hepatoblastoma biology forward but also charts a promising course toward more effective, durable cancer treatments.

As targeted therapies continue to evolve and precision medicine matures, integrating metabolic and neurotransmitter pathway modulation could redefine the landscape of cancer care. The discovery that GABA biosynthesis fosters drug resistance marks a transformative step, inspiring innovative combinatorial strategies against a devastating pediatric malignancy. It exemplifies how unraveling the complex molecular dialogues within tumors can yield actionable targets, ultimately translating benchside breakthroughs into life-saving bedside therapies.

Subject of Research: Intrinsic drug resistance mechanisms in hepatoblastoma treatment, focusing on the role of the GAD1/GABA metabolic pathway in resistance to anlotinib.

Article Title: Anlotinib mediates intrinsic drug resistance in hepatoblastoma through the GAD1/GABA pathway.

Article References:
Huang, H., Feng, Y., Xu, Y. et al. Anlotinib mediates intrinsic drug resistance in hepatoblastoma through the GAD1/GABA pathway. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04074-1

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41390-025-04074-1