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Article
Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways
This report uncovers that activation of Src lies downstream of multiple trastuzumab-resistance–driving pathways. The authors show that Src, a major mediator of PI3K and IGFR resistance pathways, also drives re...
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Article
Biomarker-guided sequential targeted therapies to overcome therapy resistance in rapidly evolving highly aggressive mammary tumors
Combinatorial targeted therapies are more effective in treating cancer by blocking by-pass mechanisms or inducing synthetic lethality. However, their clinical application is hampered by resistance and toxicity...
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Article
Open AccessCombating subclonal evolution of resistant cancer phenotypes
Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heter...
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Article
Open AccessPublisher Correction: Combating subclonal evolution of resistant cancer phenotypes
The originally published version of this Article contained an error in Figure 4. In panel a, grey boxes surrounding the subclones associated with patients #2 and #4 obscured adjacent portions of the heatmap. T...
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Article
Open AccessPan-neuroblastoma analysis reveals age- and signature-associated driver alterations
Neuroblastoma is a pediatric malignancy with heterogeneous clinical outcomes. To better understand neuroblastoma pathogenesis, here we analyze whole-genome, whole-exome and/or transcriptome data from 702 neuro...
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Article
Open AccessThe acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms
Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis. The somatic and germline genomic alterations that drive these myeloid neopla...
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Article
Chemotherapy and mismatch repair deficiency cooperate to fuel TP53 mutagenesis and ALL relapse
Chemotherapy is a standard treatment for pediatric acute lymphoblastic leukemia (ALL), which sometimes relapses with chemoresistant features. However, whether acquired drug-resistance mutations in relapsed ALL...
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Article
Open AccessNovel temporal and spatial patterns of metastatic colonization from breast cancer rapid-autopsy tumor biopsies
Metastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood.
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Article
Open AccessThe chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma
Survival in high-risk pediatric neuroblastoma has remained around 50% for the last 20 years, with immunotherapies and targeted therapies having had minimal impact. Here, we identify the small molecule CX-5461 ...
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Article
Open AccessThe landscape of coding RNA editing events in pediatric cancer
RNA editing leads to post-transcriptional variation in protein sequences and has important biological implications. We sought to elucidate the landscape of RNA editing events across pediatric cancers.
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Article
Open AccessConvergent evolution and multi-wave clonal invasion in H3 K27-altered diffuse midline gliomas treated with a PDGFR inhibitor
The majority of diffuse midline gliomas, H3 K27-altered (DMG-H3 K27-a), are infiltrating pediatric brain tumors that arise in the pons with no effective treatment. To understand how clonal evolution contribute...
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Article
The genomic landscape of pediatric acute lymphoblastic leukemia
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a generally low ...
