Daniel Bexell

De novo Design of Macrocyclic Molecular Glues

Andrä Brunner, Krzysztof Wierbiłowicz, Diandra Daumiller, Daniel Bexell et autres

Abstract The engineering of induced proximity has transformed drug discovery, yet the development of molecular glues remains largely serendipitous and restricted to the retrospective optimisation of accidental discoveries. Here, we present EvoBind-multimer, a deep learning framework for the de novo design of …

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Repurposing statins and phenothiazines to treat chemoresistant neuroblastoma

Katarzyna Radke, Kristina Aaltonen, Erick Andrés Muciño-Olmos, Javanshir Esfandyari et autres

Relapse and treatment resistance are common in children with high-risk neuroblastoma, and novel therapies are needed. Conventional drug discovery is slow, expensive, often fails in practice, and consequently falls short in addressing pediatric and rare conditions. In such instances, drug repurposing is …

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Targeted ferroptosis induction enhances chemotherapy efficacy in chemoresistant neuroblastoma

Adriana Mañas, Alexandra Seger, Aleksandra Adamska, Kyriaki Smyrilli et autres

Neuroblastoma (NB) is an aggressive pediatric solid tumor which often develops chemoresistance. Ferroptosis is a potential vulnerability in NB, but its interplay with chemoresistance and standard-of-care chemotherapy is not known. Here, we report that key antioxidant pathways are enriched in refractory NB, …

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Identification of a small molecule targeting EPLIN as a novel strategy for the treatment of pediatric neuroblastoma and medulloblastoma

Emma Lindell, Jing Guo, Miao Zhao, Natallia Rameika et autres

Amplification of the MYCN proto-oncogene serves as a key marker of aggressive disease and poor treatment outcomes in certain pediatric tumors originating from the nervous system, including neuroblastoma and medulloblastoma. However, the complex nature of the challenging MYCN protein underscores the urgent …

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Evolutionary unpredictability in cancer model systems

Subhayan Chattopadhyay, Jenny Karlsson, Michele Ferro, Adriana Mañas et autres

Despite the advent of advanced molecular prognostic tools, it is still difficult to predict the course of disease for cancer patients at the individual level. This lack of predictability is also reflected in many experimental cancer model systems, begging the question of …

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Evaluation of TRPA1 as a Therapeutic Target in MYCN‐Amplified Neuroblastoma

Alexandra Seger, Dora Adamič, E. Olmos, Sofía Granados-Aparici et autres

BACKGROUND: Neuroblastoma (NB) is a childhood cancer with a high relapse rate despite intensive treatment. TRPA1 is a pain-sensing ion channel with downstream impacts on proliferative and pro-apoptotic pathways. Here, we evaluated TRPA1 expression in NB and performed pharmacological inhibition in preclinical …

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Repurposing statins and phenothiazines to treat chemoresistant neuroblastoma

Katarzyna Radke, Kristina Aaltonen, Erick Andrés Muciño-Olmos, Javanshir Esfandyari et autres

Abstract Relapse and treatment resistance are common in children with high-risk neuroblastoma, and novel therapies are needed. Conventional drug discovery is slow, expensive, often fails in practice, and consequently falls short in addressing pediatric and rare conditions. In such instances, drug repurposing …

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Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma

Jenny Karlsson, Hiroaki Yasui, Adriana Mañas, Natalie Andersson et autres

Neuroblastoma (NB) is one of the most lethal childhood cancers due to its propensity to become treatment resistant. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of …

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Abstract A078 Targeted ferroptosis induction enhances chemotherapy and natural killer cell immunotherapy in neuroblastoma

Adriana Mañas, Alexandra Seger, Aleksandra Adamska, Kyriaki Smyrilli et autres

Abstract Background Neuroblastoma (NB) is a heterogeneous pediatric solid tumor of the sympathetic nervous system that accounts for 15% of pediatric childhood deaths. High-risk NB is often chemoresistant, with <50% survival. Additionally, its low mutational load and immunosuppressive tumor microenvironment (i-TME) have …

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Breast cancer associated CD169+ macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells

Fríða Björk Gunnarsdóttir, Oscar Briem, Aida Yifter Lindgren, Eva Källberg et autres

CD169+ resident macrophages in lymph nodes of breast cancer patients are for unknown reasons associated with a beneficial prognosis. This contrasts CD169+ macrophages present in primary breast tumors (CD169+ TAMs), that correlate with a worse prognosis. We recently showed that these CD169+ …

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Data from Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma

Noémie Braekeveldt, Kristoffer von Stedingk, Susanne Fransson, Angela Martinez‐Monleon et autres

Abstract Patient-derived xenografts (PDX) and the Avatar, a single PDX mirroring an individual patient, are emerging tools in preclinical cancer research. However, the consequences of intratumor heterogeneity for PDX modeling of biomarkers, target identification, and treatment decisions remain underexplored. In this study, …

Figure S1 from Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma

Noémie Braekeveldt, Kristoffer von Stedingk, Susanne Fransson, Angela Martinez‐Monleon et autres

Supplementary Figure S1. Related to Figure 3. Correlation of PDOX gene signatures to overall survival.