Готові списки джерел за темами / BRAF isoforms

Добірка наукової літератури з теми "BRAF isoforms"

Автор: Grafiati

Опубліковано: 14 березня 2023

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Статті в журналах з теми "BRAF isoforms"

Marranci, Andrea, Andrea Tuccoli, Marianna Vitiello, Elisa Mercoledi, Samanta Sarti, Simone Lubrano, Monica Evangelista, et al. "Identification of BRAF 3′UTR Isoforms in Melanoma." Journal of Investigative Dermatology 135, no. 6 (June 2015): 1694–97. http://dx.doi.org/10.1038/jid.2015.47.

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Bayer, Abraham L., Jodie Pietruska, Jaymes Farrell, Siobhan McRee, Pilar Alcaide, and Philip W. Hinds. "AKT1 Is Required for a Complete Palbociclib-Induced Senescence Phenotype in BRAF-V600E-Driven Human Melanoma." Cancers 14, no. 3 (January 23, 2022): 572. http://dx.doi.org/10.3390/cancers14030572.

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Cellular senescence is a carefully regulated process of proliferative arrest accompanied by functional and morphologic changes. Senescence allows damaged cells to avoid neoplastic proliferation; however, the induction of the senescence-associated secretory phenotype (SASP) can promote tumor growth. The complexity of senescence may limit the efficacy of anti-neoplastic agents, such as CDK4/6 inhibitors (Cdk4/6i), that induce a senescence-like state in tumor cells. The AKT kinase family, which contains three isoforms that play both unique and redundant roles in cancer progression, is commonly hyperactive in many cancers including melanoma and has been implicated in the regulation of senescence. To interrogate the role of AKT isoforms in Cdk4/6i-induced cellular senescence, we generated isoform-specific AKT knockout human melanoma cell lines. We found that the CDK4/6i Palbociclib induced a form of senescence in these cells that was dependent on AKT1. We then evaluated the activity of the cGAS-STING pathway, recently implicated in cellular senescence, finding that cGAS-STING function was dependent on AKT1, and pharmacologic inhibition of cGAS had little effect on senescence. However, we found SASP factors to require NF-κB function, in part dependent on a stimulatory phosphorylation of IKKα by AKT1. In summary, we provide the first evidence of a novel, isoform-specific role for AKT1 in therapy-induced senescence in human melanoma cells acting through NF-κB but independent of cGAS.

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Tadijan, Ana, Francesca Precazzini, Nikolina Hanžić, Martina Radić, Nicolò Gavioli, Ignacija Vlašić, Petar Ozretić, et al. "Altered Expression of Shorter p53 Family Isoforms Can Impact Melanoma Aggressiveness." Cancers 13, no. 20 (October 18, 2021): 5231. http://dx.doi.org/10.3390/cancers13205231.

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Cutaneous melanoma is the most aggressive form of skin cancer. Despite the significant advances in the management of melanoma in recent decades, it still represents a challenge for clinicians. The TP53 gene, the guardian of the genome, which is altered in more than 50% of human cancers, is rarely mutated in melanoma. More recently, researchers started to appreciate the importance of shorter p53 isoforms as potential modifiers of the p53-dependent responses. We analyzed the expression of p53 and p73 isoforms both at the RNA and protein level in a panel of melanoma-derived cell lines with different TP53 and BRAF status, in normal conditions or upon treatment with common anti-cancer DNA damaging agents or targeted therapy. Using lentiviral vectors, we also generated stable clones of H1299 p53 null cells over-expressing the less characterized isoforms Δ160p53α, Δ160p53β, and Δ160p53γ. Further, we obtained two melanoma-derived cell lines resistant to BRAF inhibitor vemurafenib. We observed that melanoma cell lines expressed a wide array of p53 and p73 isoforms, with Δ160p53α as the most variable one. We demonstrated for the first time that Δ160p53α, and to a lesser extent Δ160p53β, can be recruited on chromatin, and that Δ160p53γ can localize in perinuclear foci; moreover, all Δ160p53 isoforms can stimulate proliferation and in vitro migration. Lastly, vemurafenib-resistant melanoma cells showed an altered expression of p53 and p73 isoforms, namely an increased expression of potentially pro-oncogenic Δ40p53β and a decrease in tumor-suppressive TAp73β. We therefore propose that p53 family isoforms can play a role in melanoma cells’ aggressiveness.

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Vlašić, Ignacija, Anđela Horvat, Ana Tadijan, and Neda Slade. "p53 Family in Resistance to Targeted Therapy of Melanoma." International Journal of Molecular Sciences 24, no. 1 (December 21, 2022): 65. http://dx.doi.org/10.3390/ijms24010065.

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Metastatic melanoma is one of the most aggressive tumors, with frequent mutations affecting components of the MAPK pathway, mainly protein kinase BRAF. Despite promising initial response to BRAF inhibitors, melanoma progresses due to development of resistance. In addition to frequent reactivation of MAPK or activation of PI3K/AKT signaling pathways, recently, the p53 pathway has been shown to contribute to acquired resistance to targeted MAPK inhibitor therapy. Canonical tumor suppressor p53 is inactivated in melanoma by diverse mechanisms. The TP53 gene and two other family members, TP63 and TP73, encode numerous protein isoforms that exhibit diverse functions during tumorigenesis. The p53 family isoforms can be produced by usage of alternative promoters and/or splicing on the C- and N-terminus. Various p53 family isoforms are expressed in melanoma cell lines and tumor samples, and several of them have already shown to have specific functions in melanoma, affecting proliferation, survival, metastatic potential, invasion, migration, and response to therapy. Of special interest are p53 family isoforms with increased expression and direct involvement in acquired resistance to MAPK inhibitors in melanoma cells, implying that modulating their expression or targeting their functional pathways could be a potential therapeutic strategy to overcome resistance to MAPK inhibitors in melanoma.

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Dillon, Martha, Antonio Lopez, Edward Lin, Dominic Sales, Ron Perets, and Pooja Jain. "Progress on Ras/MAPK Signaling Research and Targeting in Blood and Solid Cancers." Cancers 13, no. 20 (October 10, 2021): 5059. http://dx.doi.org/10.3390/cancers13205059.

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The mitogen-activated protein kinase (MAPK) pathway, consisting of the Ras-Raf-MEK-ERK signaling cascade, regulates genes that control cellular development, differentiation, proliferation, and apoptosis. Within the cascade, multiple isoforms of Ras and Raf each display differences in functionality, efficiency, and, critically, oncogenic potential. According to the NCI, over 30% of all human cancers are driven by Ras genes. This dysfunctional signaling is implicated in a wide variety of leukemias and solid tumors, both with and without viral etiology. Due to the strong evidence of Ras-Raf involvement in tumorigenesis, many have attempted to target the cascade to treat these malignancies. Decades of unsuccessful experimentation had deemed Ras undruggable, but recently, the approval of Sotorasib as the first ever KRas inhibitor represents a monumental breakthrough. This advancement is not without novel challenges. As a G12C mutant-specific drug, it also represents the issue of drug target specificity within Ras pathway; not only do many drugs only affect single mutational profiles, with few pan-inhibitor exceptions, tumor genetic heterogeneity may give rise to drug-resistant profiles. Furthermore, significant challenges in targeting downstream Raf, especially the BRaf isoform, lie in the paradoxical activation of wild-type BRaf by BRaf mutant inhibitors. This literature review will delineate the mechanisms of Ras signaling in the MAPK pathway and its possible oncogenic mutations, illustrate how specific mutations affect the pathogenesis of specific cancers, and compare available and in-development treatments targeting the Ras pathway.

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Sorokin, Alex, Lea Bitner, Ji Wu, David Menter, Scott Kopetz, and Van Karlyle Morris. "Antitumor activity of panRAF inhibition in BRAF V600E metastatic colorectal cancer." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 616. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.616.

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616 Background: BRAF V600E mutations, present in <10% of patients with metastatic colorectal cancer (mCRC), are associated with low responses to chemotherapy and poor survival outcomes. Targeted therapies against BRAF and EGFR have shown promising clinical activity. The panRAF inhibitor (PRI) LSN3074753 inhibits dimerization of all RAF isoforms to impede downstream MEK activation, with no reflexive MAPK reactivation common with other BRAF inhibitors. Anti-tumor activity of PRI has not been compared to BRAF + EGFR inhibition in patient-derived xenograft (PDX) models of BRAF V600E mCRC. Methods: Two PDX models of BRAF V600E mCRC (B1003 and C0999) were generated. C0999 featured a concomitant KRAS G12D mutation following resistance to the BRAF V600E kinase inhibitor vemurafenib. Mice were treated daily with oral PRI or with the combination of vemurafenib + intraperitoneal cetuximab. Tumor volumes were measured twice weekly. B1003 and C0999 cell cultures were established to test the interaction between PRI and palbociclib or BYL319 (PI3K inhibitor). Results: PRI was tolerated at a dose of 60 mg/kg and demonstrated a reduced tumor volume in the B1003 model after 28 days when compared to untreated controls (P=.03). No difference in tumor volume was seen between PRI and vemurafenib + cetuximab (P=.08). Assessment of anti-tumor activity by PRI in the vemurafenib-resistant BRAF V600E/KRAS G12D C0999 model will be reported. Cell culture from both the B1003 and C0999 models demonstrated synergism for PRI with palbociclib (ED50 .41 and .62 for the 2 models, respectively) and with BYL319 (ED50 .48 and .86, respectively). Conclusions: panRAF inhibition demonstrates similar anti-tumor activity to BRAF + EGFR inhibition in PDX models of BRAF V600E and represents a promising treatment strategy for further combination studies targeting additional critical signaling pathways in mCRC.

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Broseghini, Elisabetta, Emi Dika, Eric Londin, and Manuela Ferracin. "MicroRNA Isoforms Contribution to Melanoma Pathogenesis." Non-Coding RNA 7, no. 4 (September 27, 2021): 63. http://dx.doi.org/10.3390/ncrna7040063.

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Cutaneous melanoma (CM) is the most lethal tumor among skin cancers, and its incidence is constantly increasing. A deeper understanding of the molecular processes guiding melanoma pathogenesis could improve diagnosis, treatment and prognosis. MicroRNAs play a key role in melanoma biology. Recently, next generation sequencing (NGS) experiments, designed to assess small-RNA expression, revealed the existence of microRNA variants with different length and sequence. These microRNA isoforms are known as isomiRs and provide an additional layer to the complex non-coding RNA world. Here, we collected data from NGS experiments to provide a comprehensive characterization of miRNA and isomiR dysregulation in benign nevi (BN) and early-stage melanomas. We observed that melanoma and BN express different and specific isomiRs and have a different isomiR abundance distribution. Moreover, isomiRs from the same microRNA can have opposite expression trends between groups. Using The Cancer Genome Atlas (TCGA) dataset of skin cancers, we analyzed isomiR expression in primary melanoma and melanoma metastasis and tested their association with NF1, BRAF and NRAS mutations. IsomiRs differentially expressed were identified and catalogued with reference to the canonical form. The reported non-random dysregulation of specific isomiRs contributes to the understanding of the complex melanoma pathogenesis and serves as the basis for further functional studies.

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Ngeow, Kao Chin, Hans J. Friedrichsen, Linxin Li, Zhiqiang Zeng, Sarah Andrews, Laurent Volpon, Hannah Brunsdon, et al. "BRAF/MAPK and GSK3 signaling converges to control MITF nuclear export." Proceedings of the National Academy of Sciences 115, no. 37 (August 27, 2018): E8668—E8677. http://dx.doi.org/10.1073/pnas.1810498115.

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The close integration of the MAPK, PI3K, and WNT signaling pathways underpins much of development and is deregulated in cancer. In principle, combinatorial posttranslational modification of key lineage-specific transcription factors would be an effective means to integrate critical signaling events. Understanding how this might be achieved is central to deciphering the impact of microenvironmental cues in development and disease. The microphthalmia-associated transcription factor MITF plays a crucial role in the development of melanocytes, the retinal pigment epithelium, osteoclasts, and mast cells and acts as a lineage survival oncogene in melanoma. MITF coordinates survival, differentiation, cell-cycle progression, cell migration, metabolism, and lysosome biogenesis. However, how the activity of this key transcription factor is controlled remains poorly understood. Here, we show that GSK3, downstream from both the PI3K and Wnt pathways, and BRAF/MAPK signaling converges to control MITF nuclear export. Phosphorylation of the melanocyte MITF-M isoform in response to BRAF/MAPK signaling primes for phosphorylation by GSK3, a kinase inhibited by both PI3K and Wnt signaling. Dual phosphorylation, but not monophosphorylation, then promotes MITF nuclear export by activating a previously unrecognized hydrophobic export signal. Nonmelanocyte MITF isoforms exhibit poor regulation by MAPK signaling, but instead their export is controlled by mTOR. We uncover here an unanticipated mode of MITF regulation that integrates the output of key developmental and cancer-associated signaling pathways to gate MITF flux through the import–export cycle. The results have significant implications for our understanding of melanoma progression and stem cell renewal.

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Farrell, Jaymes, Jodie Pietruska, Siobhan McRee, Philip Tsichlis, and Philip Hinds. "Abstract PR14: Defining isoform-specific roles for AKTs in BRAFV600E-driven melanoma." Cancer Research 80, no. 19_Supplement (October 1, 2020): PR14. http://dx.doi.org/10.1158/1538-7445.mel2019-pr14.

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Abstract The PI3K/AKT pathway is frequently dysregulated in cutaneous melanoma and impacts both tumor aggression and resistance to BRAFV600E/K inhibitors. While current clinical approaches to AKT inhibition are severely limited by the toxicity of pan-AKT inhibitors, selective inhibition of individual AKT isoforms (AKT1, AKT2, or AKT3) remains an attractive, if yet unattainable, approach. A critical gap in our understanding concerns how the three highly homologous yet functionally distinct AKT isoforms contribute to melanomagenesis and treatment response. To address this question, we are employing RNAi and gene editing approaches to interrogate the effect of selective suppression or CRISPR/Cas9-mediated deletion of each isoform in vitro, as well as the impact of AKT isoform loss on 1) the growth of melanoma xenografts and 2) the development of spontaneous tumors in a melanoma-prone mouse model. In addition, we are interrogating tumor-promoting functions of AKT isoform-selective substrates recently identified in a phospho-proteomic screen of mouse fibroblasts, a system that allows us to identify downstream actionable targets that may mediate the effects of AKT isoforms in tumorigenesis. Broadly, we are focusing on the importance of AKTs in tumor cell growth, metastasis, and response to inhibitors of BRAFV600E/K or CDK4/6. We find that loss of AKT1 impacts growth of BRAF mutant human melanoma cells both in vitro and in vivo. Additionally, AKT1 appears to play an isoform-specific role in response to pharmacologic CDK4/6 inhibition, impacting transcriptional and morphologic changes typically associated with permanent cell cycle arrest. In contrast, loss of AKT2 has a minimal impact on melanoma cell growth or response to CDK4/6 inhibition, but severely limits the development of metastatic disease, potentially through a combination of impaired seeding at the metastatic site and defects in glycolysis. While AKT3 loss does not appreciably impact the above-mentioned cellular phenotypes, the protumorigenic role of AKT3 may involve activation of broadly-acting neutral proteases previously implicated in cell cycle progression, cell migration, and CDK5 regulation. Taken together, we provide evidence for distinct roles for AKT isoforms in several aspects of the tumorigenic process as well as response to current therapies. Future studies will focus on identification and targeting of the relevant downstream mediators of these phenotypes. This abstract is also being presented as Poster A16. Citation Format: Jaymes Farrell, Jodie Pietruska, Siobhan McRee, Philip Tsichlis, Philip Hinds. Defining isoform-specific roles for AKTs in BRAFV600E-driven melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr PR14.

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Journal, Baghdad Science. "Detection of RAF fusion transcripts in FFPE samples of Medullablastoma and Ependymom in Iraqi children with RT-RQPCR assays." Baghdad Science Journal 11, no. 3 (September 7, 2014): 1411–19. http://dx.doi.org/10.21123/bsj.11.3.1411-1419.

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Medulloblastomas and ependymomas are the most common malignant brain tumors in children. However genetic abnormalities associated with their development and prognosis remain unclear. Recently two gene fusions, KIAA1549–BRAF and SRGAP3–RAF1 have been detected in a number of brain tumours. We report here our development and validation of RT-RQPCR assays to detect various isoforms of these two fusion genes in formalin fixed paraffin embedded (FFPE) tissues of medulloblastoma and ependymoma. We examined these fusion genes in 44 paediatric brain tumours, 33 medulloblastomas and 11 ependymomas. We detected both fusion transcripts in 8/33, 5/33 SRGAP3 ex10/RAF1 ex10, and 3/33 KIAA1549 ex16/BRAF ex9, meduloblastomas but none in the 11 ependymomas examined. This investigation provided evidence to the value of RT-RQPCR assays for the detection of these fusion genes in large-scale studies on FFPE tissues. The study also reports the first detection of RAF fusion genes in meduloblstomas.

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Більше джерел

Дисертації з теми "BRAF isoforms"

Duggan, Megan C. "The Role of Novel NRAS Isoforms in Melanoma Disease Progression and BRAF Inhibitor Resistance." The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1491229758308229.

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LUBRANO, SIMONE. "Yeast S. cerevisiae as a tool to study BRAFV600E kinase isoforms." Doctoral thesis, Università di Siena, 2018. http://hdl.handle.net/11365/1040150.

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BRAFV600E causes an altered regulation of the MAPK pathway (mitogen-activated protein kinase or RAS / RAF / MEK / ERK pathway), involved in cell division and differentiation. This mutation consists of the substitution of a valine with glutamic acid at position 600 (V600E), resulting in a change in conformation, responsible for a constitutive activation of the protein, even in the presence of a low level of RAS, its activator. In this work we have demonstrated, for the first time, that hBRAFV600E kinase activity is preserved and can be studied in yeast. Indeed, hBRAFV600E complements the activity of MAPKKK kinases belonging to the osmotic stress (HOG) pathway and is toxic in yeast strains deleted for phosphatases of the same pathway. Moreover, we have demonstrated that a yeast genetic context allows the one-by-one analysis of the 3 BRAF protein isoforms that always coexist in human cells (BRAF-Ref, BRAF-X1 and BRAF-X2). In addition, we provide experimental evidence that yeast can be used to perform high throughput screenings and identify new BRAFV600E functional interactors. In fact, two screenings have been performed in this model system, one using a cDNA Library and another one taking advantage of the Yeast Deletion Pool collection. The screening performed with the cDNA library, deriving from HeLa cells, was performed in a yeast strain deleted for two phosphates PTC1 and PTP3. ~105 transformed cells have been screened. We obtained 16 complete CDS, 13 out of 16 have been validated using the spot assay. Among them, we found the Small Integral Membrane Protein 10 (SMIM10), a protein of unknown function that has been further characterized because of its different expression levels in human melanoma cell lines with mutated BRAF as compared to those with wild type (wt) BRAF. Interestingly, SMIM10 overexpression causes a dramatic decrease in the levels of BRAFV600E both in yeast and in human cells. These results suggest that SMIM10 is a negative functional interactors (FI) of BRAFV600E with a possible oncosuppressive role. The second screening was performed using the Yeast Deletion Pool, a pool of yeast S. cerevisiae clones, that has a deletion in non-essential genes (4,741 clones). Each clone is identifiable by means of two specific DNA sequences called "barcodes". 4 Through the use of the yeast deletion pool, it is possible to identify functional interactors of proteins related to diseases which do not have homologous counterparts in yeast, such as BRAF. As a result of this screening, we have identified 9 genes affecting the fitness of cells expressing BRAFV600E-X1/Ref, compared to cells transformed with the empty vector. Four out of nine affected the fitness with both isoforms. Interestingly, among deleted genes altering the fitness of BRAFV600E expressing cells when deleted, there are RAS, a SWI/SNF remodeling factor and Arf2 (GTPase). The addition of salt to the growth of the YDP highlighted differences between the two isoforms. In fact, while the comparison pYES2-BRAFV600E-Ref versus pYES2-BRAFV600E-Ref + NaCl showed differences in 4 clones, the comparison of pYES2-BRAFV600E-X1 versus pYES2-BRAFV600E-X1+ NaCl showed differences in 21 clones. Among them, an ABC transporter, a Rho GTPase, and a subunit of TORC2 membrane-associated complex have been found. Finally, this work has yielded a list of modulators of BRAFV600E to be further characterized experimentally and eventually translated into innovative therapeutic strategies that could be used in addition to the existing BRAF inhibitors.

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Alatawi, Abdullah Salem S. "Alternative Splicing of MDM4 in Human Melanomas." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1598021739996938.

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Valluet, Agathe. "Utilisation de modèles murins pour l'étude du rôle physiologique des isoformes de BRaf et du rôle des protéines Raf dans le lignage mélanocytaire." Paris 7, 2010. http://www.theses.fr/2010PA077167.

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Le laboratoire s'intéresse à la voie de signalisation ERK, particulièrement aux protéines Raf (ARaf, BRaf et I CRaf). Nous avons montré que le gène BRAF codait de multiples isofbrmes présentant une expression tissu-j spécifique. La présence des séquences codées par les exons 8b/9b module les propriétés biochimiques et I oncogéniques de BRaf Mon projet de recherche a consisté à analyser le phénotype de souris knockout dans | lesquelles chacun des exons a été invalidé. Les résultats ont montré que l'épissage alternatif n'est pas essentiel pour I le développement ni pour la myélination du cerveau. Des analyses comportementales ont mis en évidence que l'expression des isoformes contenant l'exon 9b, et pas celles contenant l'exon 8b, était requise pour les mécanismes de mémoire et d'apprentissage dépendants de l'hippocampe. Le gène BRAF est muté dans 50% des mélanomes cutanés. Mon deuxième projet de thèse a consisté à générer et analyser le phénotype de souris mutées pour BRaf et CRaf dans les mélanocytes. Les souris ne présentent pas de défaut de pigmentation à la naissance, BRaf et CRaf ne sont donc pas requis pour l'homéostasie des mélanoblastes (MB). Cependant, les souris développent un phénotype de blanchiment du poil causé par une perte des cellules souches mélanocytaires (MSC). Les protéines Raf sont donc impliquées dans l'autorenouvellement des MSC, indépendantes de la signalisation en aval de Kit, tandis que les MB sont dépendants de cette signalisation et ne présentent pas de défaut particulier dans nos souris. Ces observations révèlent un découplage imprévu entre les signalisations Kit et ERK dans les cellules mélanocytaires
Our team works on the ERK pathway and we mainly focus on the Raf proteins family. We have demonstrated that the BRAF gene encoded several isoforms resulting from alternative splicing of exons 8b and 9b. The presence of these sequences modulates the biochemical and oncogenic properties of the protein. The aim of my project was to analyse the phenotype of knockout mice for each £/to/alternatively spliced exons. Constitutive ablation revealed no obvious defects during embryogenesis and adulthood. However, behavioural analyses revealed a specific role for exon 9b-containing BRaf isoforms in certain types of hippocampal-dependent learning and memory. BRaf and CRaf protein kinases have recently emerged as critical players in cutaneous melanoma but little is known about their putative role in the melanocyte lineage in vivo. The aim of my second project was to analyse the phenotype of mice deleted for both BRaf and CRaf in this lineage. Surprisingly, the double knockouts displayed normal pigmentation at birth and did not show signifîcant defect in melanoblasts. However, fbllowing the first hair | molting, the double knockout animals unveiled a progressive hair graying phenotype resulting from depletion of j melanocyte stem cells (MSC). In vitro cultures of melanocytic cells derived from knockout animals could not sustain growth in the presence of TPA but proliferated in the presence of the Kit ligand, SCF. Taken together, our results show that Raf signalling is required for proper MSC maintenance, but dispensable for early melanocyte lineage development. Our observations reveal an unexpected uncoupling between Kit and Raf signalling in the melanocyte lineage

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Тези доповідей конференцій з теми "BRAF isoforms"

McRee, Siobhan K., Jodie R. Pietruska, Elisabeth Dignan, and Philip W. Hinds. "Abstract B07: Differential roles for AKT isoforms in BRAF mutant melanoma." In Abstracts: AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1557-3265.pmccavuln16-b07.

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Poulikakos, Poulikos I. "Abstract PR-1: Acquired resistance to RAF inhibitors is mediated by splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1535-7163.targ-11-pr-1.

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Peng, Sheng-Bin, James Henry, Michael Kaufman, Wei-Ping Lu, Bryan D. Smith, Subha Vogeti, Scott Wise, et al. "Abstract DDT02-02: Identification of LY3009120 as a pan inhibitor of Raf isoforms and dimers with minimal paradoxical activation and activities against BRaf or Ras mutant tumor cells." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-ddt02-02.

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Duggan, Megan, Andrew Stiff, Gonzalo Olaverria Salavaggione, Maryam Bainazar, Nicholas Latchana, Joseph Markowitz, Albert de la Chapelle, Ann-Kathrin Eisfeld, and William Carson. "Abstract 301: Identification of NRAS isoform 2 overexpression as a novel mechanism facilitating BRAF inhibitor resistance in malignant melanoma (MM)." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-301.

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