Top 10 Biorxiv Papers Today in Cancer Biology


2.03 Mikeys
#1. Development of Human Neuroblastomas in Mouse-Human Neural Crest Chimeras
Malkiel A. Cohen, Shupei Zhang, Satyaki Sengupta, Haiting Ma, Brendan Horton, George W. Bell, Rani E. George, Stefani Spranger, Rudolf Jaenisch
Neuroblastoma (NB), derived from the neural crest (NC), is the most common pediatric extracranial solid tumor. Here we establish a platform that allows studying human NBs in mouse-human NC chimeras. Chimeric mice were produced by injecting human NC cells carrying NB relevant oncogenes in-utero into gastrulating mouse embryos. The mice developed tumors composed of a heterogenous cell population that closely resembled that seen in primary NBs of patients but were significantly different from homogenous tumors formed in xenotransplantation models. The human tumors emerged in immunocompetent hosts and were extensively infiltrated by mouse cytotoxic T cells reflecting a vigorous host anti-tumor immune response. However, the tumors blunted the immune response by inducing infiltration of regulatory T cells and expression of immune checkpoints similar to escape mechanisms seen in human cancer patients. Thus, this experimental platform allows studying human tumor initiation, progression, manifestation and tumor - immune-system interactions...
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biorxivpreprint: Development of Human Neuroblastomas in Mouse-Human Neural Crest Chimeras https://t.co/IAH7D3j2qs #bioRxiv
Aiims1742: This is quite an approach to generate genetically engineered animal models from the Jaenisch lab. Creating mouse chimeras by injecting embryos with human neural crest cells carrying neuroblastoma oncogenes. The resulting tumors escape host immune responses https://t.co/MX0Ub74SnB https://t.co/FKB19bwsH6
CyrilPedia: Meanwhile, in the Jaenisch lab "Development of Human Neuroblastomas in Mouse-Human Neural Crest Chimeras" https://t.co/3WqHksolR1
biorxiv_cancer: Development of Human Neuroblastomas in Mouse-Human Neural Crest Chimeras https://t.co/1rHcWwzC7s #biorxiv_cancer
malkiel_cohen: My first preprint! Using mouse-human neural crest chimeras, we model the development of human Neuroblastomas and it immune-microenvironment, in vivo. @shupei_Zhang https://t.co/fha4vGIIPX
Shupei_Zhang: Check out @malkiel_cohen paper on studying #neuroblastoma in a mouse-human chimeric model with immune regulations https://t.co/1Rsigtyb8k
yicheng_wu: Check out the great work by Jaenisch’s lab ⁦@Shupei_Zhang⁩ https://t.co/2aoxNqUsKn
YichengWu1: RT @yicheng_wu: Check out the great work by Jaenisch’s lab ⁦@Shupei_Zhang⁩ https://t.co/2aoxNqUsKn
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Sample Sizes : None.
Authors: 9
Total Words: 9795
Unqiue Words: 3283

2.0 Mikeys
#2. Molecular and functional heterogeneity of cancer associated fibroblasts in high-grade serous ovarian cancer
Ali Hussain, Veronique Voisin, Stephanie Poon, Julia Dmytryshyn, Jalna Meens, Joshua Paterson, Blaise Clarke, Marcus Bernardini, Gary Bader, Benjamin Neel, Laurie Ailles
Recent studies indicate that cancer-associated fibroblasts (CAFs) are phenotypically and functionally heterogeneous. However, little is known about CAF subtypes and the roles they play in cancer progression. Here we identify and characterize two CAF subtypes that coexist within high grade serous ovarian cancers: Fibroblast activation protein (FAP)-high (FH) CAFs resemble the classical myofibroblast-type CAF, whereas FAP-low (FL) CAFs possesses a preadipocyte-like molecular signature. Patients with predominantly FH CAFs have significantly worse outcomes than patients with predominantly FL CAFs. FH CAFs contract collagen gels and aggressively promote proliferation, invasion and therapy resistance of cancer cells, whereas FL CAFs do not. Overexpression of the FL-specific transcription factor TCF21 in FH CAFs dampens their ability to promote gel contraction, invasion, and in vivo tumor growth. Understanding CAF subtypes in more detail could lead to better patient stratification and novel therapeutic strategies.
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lawrensonlab: Beautiful study showing that CAFs are not all created equal in #ovariancancer #bioRxiv https://t.co/zQ9hCSGVCo
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Sample Sizes : [3, 2, 3, 80, 30, 23, 23, 3, 4, 5, 3, 5, 5, 3, 10, 12]
Authors: 11
Total Words: 15488
Unqiue Words: 3968

1.998 Mikeys
#3. Acute Myeloid Leukemia Driven by the CALM-AF10 Fusion Gene is Dependent on BMI1
Karina Barbosa, Anwesha Ghosh, Anagha Deshpande, Bo-Rui Chen, Younguk Sun, Marla Weetall, Scott A Armstrong, Stefan K Bohlander, Aniruddha J Deshpande
A subset of acute myeloid and lymphoid leukemia cases harbor a t(10;11)(p13;q14) translocation resulting in the CALM-AF10 fusion gene. Standard chemotherapeutic strategies are often ineffective in treating patients with CALM-AF10 fusions. Hence, there is an urgent need to identify molecular pathways dysregulated in CALM-AF10-positive leukemias which may lay the foundation for novel targeted therapies. Here we demonstrate that the Polycomb Repressive Complex 1 gene BMI1 is consistently overexpressed in adult and pediatric CALM-AF10-positive leukemias. We demonstrate that genetic Bmi1 depletion abrogates CALM-AF10-mediated transformation of murine hematopoietic stem and progenitor cells (HSPCs). Furthermore, CALM-AF10-positive murine and human AML cells are profoundly sensitive to the small-molecule BMI1 inhibitor PTC209 as well as to PTC596, a compound in clinical development that has been shown to result in downstream degradation of BMI1 protein. PTC-596 significantly prolongs survival of mice injected with a human CALM-AF10 cell...
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Jesse_R_Dixon: RT @biorxivpreprint: Acute Myeloid Leukemia Driven by the CALM-AF10 Fusion Gene is Dependent on BMI1 https://t.co/BVQ1ENs7t4 #bioRxiv
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Sample Sizes : [5, 2, 3, 3, 3, 2, 9, 9, 2, 6, 3, 3, 5, 6, 27, 167, 1202]
Authors: 9
Total Words: 8010
Unqiue Words: 2467

0.0 Mikeys
#4. Intermittent hormonal therapy shows similar outcome than SOC in ER+ breast cancer preclinical model.
Pedro M. Enriquez Navas, Libia Garcia, Mahmoud Abdalah, Olya Stringfield, Kim Luddy, Sabrina Hassan, Robert J Gillies, Robert A Gatenby
Clinical breast cancers in which at least 10% of cells express the estrogen receptor are labeled as "ER positive". First line therapy for these patients is typically continuous administration of anti-estrogen drugs at maximum tolerated dose (MTD) until progression. In the vast majority of patients, resistance to hormone therapy evolves in the breast cancer cells within 2 years leading to treatment failure and tumor progression. In prior studies, we have demonstrated continuous application of MTD chemotherapy results in evolutionary dynamics (termed "competitive release") that accelerates proliferation of treatment-resistance populations. In contrast, evolution-informed application of treatment reduces drug administration to maintain substantial populations of therapy-sensitive cells to reduce proliferation of resistant phenotypes. Prior pre-clinical and clinical studies have shown this strategy can delay or prevent proliferation of resistant cells and prolong time to progression (TTP). We hypothesize that similar dynamics may be...
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biorxivpreprint: Intermittent hormonal therapy shows similar outcome than SOC in ER+ breast cancer preclinical model. https://t.co/Ur23eR4hSH #bioRxiv
biorxiv_cancer: Intermittent hormonal therapy shows similar outcome than SOC in ER+ breast cancer preclinical model. https://t.co/sxSnj1r4hj #biorxiv_cancer
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Sample Sizes : [14, 41]
Authors: 8
Total Words: 5511
Unqiue Words: 1972

0.0 Mikeys
#5. Inducible formation of leading cells driven by CD44 switching gives rise to collective invasion
Cuixia Yang, Manlin Cao, Yiwen Liu, Yiqing He, Yan Du, Guoliang Zhang, Feng Gao
Collective invasion into adjacent tissue is a hallmark of luminal breast cancer, with about 20% of cases that eventually undergo metastasis. It remained unclear how less aggressive luminal-like breast cancer transit to invasive cancer. Our study revealed that CD44hi cancer cells are the leading subpopulation in collective invading cancer cells, which could efficiently lead the collective invasion of CD44lo/follower cells. CD44hi/leading subpopulation showed specific gene signature of a cohort of hybrid epithelial/mesenchymal state genes and key functional co-regulators of collective invasion, which was distinct from CD44lo/follower cells. However, the CD44hi/leading cells, in partial-EMT state, were readily switching to CD44lo phenotype along with collective movements and vice versa, which is spontaneous and sensitive to tumor microenvironment. The CD44lo-to-CD44hi conversion is accompanied with a shift of CD44s-to-CD44v, but not corresponding to the conversion of non-CSC-to-CSC. Therefore, the CD44hi leader cells are not a stable...
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Sample Sizes : None.
Authors: 7
Total Words: 12146
Unqiue Words: 3547

0.0 Mikeys
#6. Targeting Wnt Signaling To Overcome PARP Inhibitor Resistance
Tomomi M Yamamoto, Alexandra McMellen, Zachary L Watson, Jennifer Aguilera, Matthew J Sikora, Rebecca Ferguson, Elmar Nurmemmedov, Tanay Thakar, Moldovan George-Lucian, Hyunmin Kim, Diana M Cittelly, Heidi Wilson, Kian Behbakht, Benjamin G Bitler
Epithelial ovarian cancer (EOC) has one of the highest deaths to incidence ratios. High grade serous ovarian carcinoma (HGSOC) is the most common and deadliest EOC histotype because of the lack of secondary therapeutic options following debulking surgery and platinum/taxane-based chemotherapies. For recurrent chemosensitive HGSOC, poly(ADP)-ribose polymerase inhibitors (PARPi; olaparib, rucaparib, or niraparib) represent an emerging treatment strategy. While PARPi are most effective in homologous recombination DNA repair-deficient (HRD) HGSOCs, more recent studies have observed a significant clinical benefit in non-HRD HGSOCs. However, all HGSOC patients are likely to acquire resistance to PARPi. Therefore, there is an urgent clinical need to better understand PARPi resistance, and to introduce novel combinatorial therapies to overcome PARPi resistance and extend HGSOC disease-free intervals. Utilizing a two BRCA2-mutated and one BRCA-wildtype HGSOC cell lines that are olaparib sensitive, we established resistant cells....
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biorxivpreprint: Targeting Wnt Signaling To Overcome PARP Inhibitor Resistance https://t.co/Y92jInNhh7 #bioRxiv
biorxiv_cancer: Targeting Wnt Signaling To Overcome PARP Inhibitor Resistance https://t.co/yO55qmQCTE #biorxiv_cancer
tpulinil: Retweeted bioRxiv (@biorxivpreprint): Targeting Wnt Signaling To Overcome PARP Inhibitor Resistance https://t.co/CZiz7Ewfue #bioRxiv https://t.co/CZiz7Ewfue
wntlab: RT @biorxivpreprint: Targeting Wnt Signaling To Overcome PARP Inhibitor Resistance https://t.co/Y92jInNhh7 #bioRxiv
tpulinil: RT @biorxivpreprint: Targeting Wnt Signaling To Overcome PARP Inhibitor Resistance https://t.co/Y92jInNhh7 #bioRxiv
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Sample Sizes : None.
Authors: 14
Total Words: 8681
Unqiue Words: 2769

0.0 Mikeys
#7. A mathematical approach to differentiate spontaneous and induced evolution to drug resistance during cancer treatment
James M. Greene, Jana L. Gevertz, Eduardo D. Sontag
Drug resistance is a major impediment to the success of cancer treatment. Resistance is typically thought to arise through random genetic mutations, after which mutated cells expand via Darwinian selection. However, recent experimental evidence suggests that the progression to drug resistance need not occur randomly, but instead may be induced by the treatment itself, through either genetic changes or epigenetic alterations. This relatively novel notion of resistance complicates the already challenging task of designing effective treatment protocols. To better understand resistance, we have developed a mathematical modeling framework that incorporates both spontaneous and drug-induced resistance. Our model demonstrates that the ability of a drug to induce resistance can result in qualitatively different responses to the same drug dose and delivery schedule. We have also proven that the induction parameter in our model is theoretically identifiable, and proposed an in vitro protocol which could be used to determine a treatment's...
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Authors: 3
Total Words: 14072
Unqiue Words: 3387

0.0 Mikeys
#8. Wingless promotes JNK/MMPs positive feedback loop mediate tumour microtubes expansion, glioma progression and neurodegeneration
Marta Portela, Natasha Fahey-Lozano, Sergio Casas-Tinto
Glial cells display a network of projections (cytonemes) which mediate cell to cell communication. Under pathological conditions like glioblastoma (GB), cytonemes transform into ultra-long tumour microtubes (TMs). These filopodia infiltrate through the brain, enwrap neurons and deplete wingless (Wg)/WNT, as a consequence GB progress and neurons undergo synapse loss and degeneration. Thus TMs emerge as a central cellular feature of GB which correlates with a poor prognosis in patients and animal models. Here we describe in a Drosophila model for GB the molecular mechanisms behind TMs production, infiltration and maintenance. Glial cells are initially transformed into malignant GB upon EGFR and PI3K pathways constitutive activation, afterwards GB cells establish a positive feedback loop including Wg signalling, JNK and matrix metalloproteases (MMP). In order, Frizzled1 mediates Wg signalling upregulation which activates JNK in GB. As a consequence, MMPs are upregulated and facilitate TMs infiltration in the brain, hence GB TMs...
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biorxivpreprint: Wingless promotes JNK/MMPs positive feedback loop mediate tumour microtubes expansion, glioma progression and neurodegeneration https://t.co/doestnRQIP #bioRxiv
biorxiv_cancer: Wingless promotes JNK/MMPs positive feedback loop mediate tumour microtubes expansion, glioma progression and neurodegeneration https://t.co/UpncoGlyA7 #biorxiv_cancer
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Authors: 3
Total Words: 11596
Unqiue Words: 3273

0.0 Mikeys
#9. CIC-DUX4 expression drives the development of small round cell sarcoma in transgenic zebrafish: a new model revealing a role for ETV4 in CIC-mediated sarcomagenesis
Sarah Watson, Genevieve C Kendall, Dinesh Rakheja, Matthew E McFaul, Bruce W Draper, Franck Tirode, Olivier Delattre, James F Amatruda
CIC-DUX4 sarcoma is a rare subtype of sarcoma characterized by a devastating prognosis and resistance to conventional therapeutic strategies. So far, only few models of the disease have been reported, and its biological mechanisms remain to be elucidated. We established mosaic transgenic zebrafish expressing the human CIC-DUX4 fusion under the control of the β-actin promoter. CIC-DUX4 transgenic fish rapidly developed aggressive soft tissue tumors with a high penetrance. RNAseq profiling revealed that fish tumors shared major common targets with human tumors and cell lines, including the overexpression of the Pea3 transcription factors, etv4 and etv5. Tumor development was strongly impaired in etv4-deficient zebrafish, implicating Etv4 as a critical effector of CIC-DUX4-mediated oncogenesis. Altogether, we report here the first in vivo model of CIC-DUX4 sarcoma in zebrafish, which will represent a major tool for future preclinical research.
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biorxivpreprint: CIC-DUX4 expression drives the development of small round cell sarcoma in transgenic zebrafish: a new model revealing a role for ETV4 in CIC-mediated sarcomagenesis https://t.co/0qqvXR3y80 #bioRxiv
biorxiv_cancer: CIC-DUX4 expression drives the development of small round cell sarcoma in transgenic zebrafish: a new model revealing a role for ETV4 ... https://t.co/32Lu00a54w #biorxiv_cancer
amatrudalab: Fixed the URL: New preprint from our lab: CIC-DUX4 expression drives the development of small round cell sarcoma in transgenic zebrafish https://t.co/Md7zbwOXGZ. Great collaboration with @dinesh_rakheja, Sarah Watson, @Tirode_lab and Olivier Delattre! https://t.co/Lzom6Gkfdm
DrCeSarcoma: New from @amatrudalab in #bioRxiv: the first in vivo model of CIC-DUX4 #sarcoma in zebrafish reproduces the disease and implicates ETV4 as a critical effector of CIC-DUX4-mediated oncogenesis. Congrats for developing such an exciting tumor model! https://t.co/yUXmrB83yW
dinesh_rakheja: CIC-DUX4 expression drives the development of small round cell sarcoma in transgenic zebrafish: a new model revealing a role for ETV4 in CIC-mediated sarcomagenesis https://t.co/2KrBIMh8BB @amatrudalab @genkendall #pedipath https://t.co/YZzLMabE5Z
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Sample Sizes : None.
Authors: 8
Total Words: 6501
Unqiue Words: 2394

0.0 Mikeys
#10. Targeting tumor intrinsic metabolic node in pancreatic cancer causes tumor regression, remodels extracellular matrix and sensitizes to anti-PD1 therapy.
Nikita S Sharma, Vineet K Gupta, Vanessa T Garrido, Roey Hadad, Brittany C Durden, Kousik Kesh, Bhuwan Giri, Anthony Ferrantella, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Pancreatic ductal adenocarcinoma (PDAC) is considered to be a highly immunosuppressive and heterogenous neoplasm which has extremely poor survival. Despite improved knowledge regarding the genetic background of the tumor and better understanding of the tumor microenvironment, immune checkpoint inhibitor therapy (targeting CTLA-4, PD-1, PD-L1), which has shown effect in other solid tumors, has not been very successful against PDAC. The robust desmoplastic stroma, along with an extensive extracellular matrix (ECM) that is rich in glycosaminoglycans like hyaluronan, plays an integral role in this immune evasion. Hexosamine biosynthesis pathway (HBP), a shunt pathway of glycolysis, is a metabolic node in cancer cells that can promote survival pathways (by regulating pro-oncogenic signaling via O-GlcNAc mediated protein modifications) on one hand and influence the ECM in the tumor by regulating hyaluronan synthesis on the other. The rate-limiting enzyme of the pathway, glutamine-fructose amidotransferase (GFAT1), uses glutamine and...
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sharmanikita777: Targeting tumor intrinsic metabolic node in pancreatic cancer causes tumor regression, remodels extracellular matrix and sensitizes to anti-PD1 therapy. https://t.co/Fx5BTxV8Cn
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Sample Sizes : None.
Authors: 11
Total Words: 10237
Unqiue Words: 2905

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