Cancer Research, Biochemistry, Genetics and Molecular Biology
15
Scopus Publications
686
Scholar Citations
10
Scholar h-index
10
Scholar i10-index
Scopus Publications
Unraveling Resistance Mechanisms to Gαq Pathway Inhibition in Uveal Melanoma: Insights from Signaling-Activation Library Screening Simone Lubrano, Rodolfo Daniel Cervantes-Villagrana, Nadia Arang, Elena Sofia Cardenas-Alcoser, Kuniaki Sato, Gabriela Cuesta-Margolles, Justine S. Paradis, Monica Acosta, J. Silvio Gutkind Cancers, 2026 Background/Objectives: Uveal melanoma (UVM), the leading primary intraocular cancer in adults, is driven by GNAQ/GNA11 mutations, encoding the active forms of Gαq proteins. While local treatments like surgery or radiation can control primary tumors, nearly half of patients die from metastasis. Our aim was identifying potential pathways involved in resistance to targeted therapy in UVM. Methods: Here, we screened 100 pathway-activating mutant complementary DNAs by lentiviral overexpression to identify those that enhance the survival of cancer cells in the presence of clinically relevant targeted therapies, using BAP1 wild-type UVM cells and validated the most significant results in BAP1-mutant cells. Results: This revealed JAK/STAT activation, overexpression of anti-apoptotic BCL2/BCL-XL, and dysregulated PI3K/mTOR or Hippo pathways as escape routes under MEK-ERK or FAK inhibition. Bioinformatic analysis of UVM transcriptome in TCGA further showed that high expression of the hallmark PI3K/AKT/mTOR pathway and IL6/JAK/STAT signaling correlates with poor prognosis. A similar correlation was shown by YAP and anti-apoptotic signatures. The analysis of individual representative genes from these signatures revealed that MTOR, BCL2L1 (BCL-XL), and TEAD4 gene expression are linked to poorer survival, underscoring the potential clinical impact of these adaptive pathways. Proliferation and apoptosis assay demonstrated that aberrant activation of AKT and YAP promotes resistance to FAK and MEK inhibitors. Conclusions: These findings support the adaptability of UVM lesions and suggest rational combination therapies targeting both primary GNAQ/GNA11-driven oncogenic signals and their compensatory networks as a more effective, personalized treatment approach for advanced UVM.
Inhibition of anti-apoptotic BCL2 overcomes adaptive resistance to co-targeting of the protein kinase FAK and MEK in GNAQ-driven uveal melanoma Simone Lubrano, Rodolfo Daniel Cervantes-Villagrana, Nadia Arang, Adam Officer, Sendi Rafael Adame-Garcia, Gabriela Cuesta-Margolles, Andrew E. Aplin, J. Silvio Gutkind Journal of Biological Chemistry, 2025 Uveal melanoma (UVM) is the most common eye cancer in adults, with 50% of patients developing overt metastasis that often proves fatal. The majority of UVM harbor mutations in GNAQ or GNA11, encoding constitutively active Gαq proteins. Combined inhibition of MEK and FAK downstream of Gαq has shown promising effects in UVM cells by inducing apoptotic cell death, but resistance to this strategy can occur in the clinic. Here, we aimed to identify new targets to overcome resistance to MEK + FAK inhibition (FAKi + MEKi). Reverse-phase protein array (RPPA) analysis in UVM cells treated with FAKi + MEKi showed increased levels of pro-apoptotic proteins, such as PUMA and BIM, which promoted cell death. However, we observed an adaptive increase in anti-apoptotic proteins, including BCL2, upon FAK + MEK blockade. We generated UVM cells resistant to FAKi + MEKi by prolonged exposure. Whole-exome sequencing did not reveal relevant acquired mutations; instead, resistant cells exhibit increased BCL2 levels. Moreover, expression of a stable BCL2 mutant confers resistance to both FAKi + MEKi and FAKi+"RAF-MEK clamp" (avutometinib) treatment. Of direct translational relevance, we found that an approved BCL2 inhibitor (venetoclax) displays synergistic efficacy with FAK + MEK blockade and overcomes acquired resistance, including when combined with darovasertib, a dual PKC/PKN inhibitor limiting MEK and FAK signaling that is under clinical evaluation. Our findings suggest that resistance to FAKi + MEKi in UVM cells can be driven by an adaptive upregulation of the anti-apoptotic protein BCL2, and that, in turn, BCL2 inhibitors represent a promising precision-targeted strategy to overcome FAKi + MEKi treatment resistance and improve therapeutic outcomes.
High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma Nadia Arang, Simone Lubrano, Michele Ceribelli, Damiano C. Rigiracciolo, Robert Saddawi-Konefka, Farhoud Faraji, Sydney I. Ramirez, Daehwan Kim, Frances A. Tosto, Erica Stevenson, Yuan Zhou, Zhiyong Wang, Julius Bogomolovas, Alfredo A. Molinolo, Danielle L. Swaney, Nevan J. Krogan, Jing Yang, Silvia Coma, Jonathan A. Pachter, Andrew E. Aplin, Dario R. Alessi, Craig J. Thomas, J. Silvio Gutkind Cell Reports Medicine, 2023 Uveal melanoma (UM) is the most prevalent cancer of the eye in adults, driven by activating mutation of GNAQ/GNA11; however, there are limited therapies against UM and metastatic UM (mUM). Here, we perform a high-throughput chemogenetic drug screen in GNAQ-mutant UM contrasted with BRAF-mutant cutaneous melanoma, defining the druggable landscape of these distinct melanoma subtypes. Across all compounds, darovasertib demonstrates the highest preferential activity against UM. Our investigation reveals that darovasertib potently inhibits PKC as well as PKN/PRK, an AGC kinase family that is part of the "dark kinome." We find that downstream of the Gαq-RhoA signaling axis, PKN converges with ROCK to control FAK, a mediator of non-canonical Gαq-driven signaling. Strikingly, darovasertib synergizes with FAK inhibitors to halt UM growth and promote cytotoxic cell death in vitro and in preclinical metastatic mouse models, thus exposing a signaling vulnerability that can be exploited as a multimodal precision therapy against mUM.
Whole-genome CRISPR screening identifies PI3K/AKT as a downstream component of the oncogenic GNAQ–focal adhesion kinase signaling circuitry Nadia Arang, Simone Lubrano, Damiano Cosimo Rigiracciolo, Daniela Nachmanson, Scott M. Lippman, Prashant Mali, Olivier Harismendy, J. Silvio Gutkind Journal of Biological Chemistry, 2023 G proteins and G protein-coupled receptors activate a diverse array of signal transduction pathways that promote cell growth and survival. Indeed, hot spot-activating mutations in GNAQ/GNA11, encoding Gαq proteins, are known to be driver oncogenes in uveal melanoma (UM), for which there are limited effective therapies currently available. Focal adhesion kinase (FAK) has been recently shown to be a central mediator of Gαq-driven signaling in UM, and as a result, is being explored clinically as a therapeutic target for UM, both alone and in combination therapies. Despite this, the repertoire of Gαq/FAK-regulated signaling mechanisms have not been fully elucidated. Here, we used a whole-genome CRISPR screen in GNAQ-mutant UM cells to identify mechanisms that, when overactivated, lead to reduced sensitivity to FAK inhibition. In this way, we found that the PI3K/AKT signaling pathway represented a major resistance driver. Our dissection of the underlying mechanisms revealed that Gαq promotes PI3K/AKT activation via a conserved signaling circuitry mediated by FAK. Further analysis demonstrated that FAK activates PI3K through the association and tyrosine phosphorylation of the p85 regulatory subunit of PI3K and that UM cells require PI3K/AKT signaling for survival. These findings establish a novel link between Gαq-driven signaling and the stimulation of PI3K as well as demonstrate aberrant activation of signaling networks underlying the growth and survival of UM and other Gαq-driven malignancies.
Focal Adhesion Kinase (FAK)-Hippo/YAP transduction signaling mediates the stimulatory effects exerted by S100A8/A9-RAGE system in triple-negative breast cancer (TNBC) Damiano Cosimo Rigiracciolo, Nijiro Nohata, Rosamaria Lappano, Francesca Cirillo, Marianna Talia, Sendi Rafael Adame-Garcia, Nadia Arang, Simone Lubrano, Ernestina Marianna De Francesco, Antonino Belfiore, J. Silvio Gutkind, Marcello Maggiolini Journal of Experimental and Clinical Cancer Research, 2022 BackgroundUnderstanding the intricate signaling network involved in triple-negative breast cancer (TNBC) represents a challenge for developing novel therapeutic approaches. Here, we aim to provide novel mechanistic insights on the function of the S100A8/A9-RAGE system in TNBC.MethodsTNM plot analyzer, Kaplan-Meier plotter, Meta-analysis, GEPIA2 and GOBO publicly available datasets were used to evaluate the clinical significance of S100A8/A9 and expression levels of S100A8/A9, RAGE and Filamin family members in breast cancer (BC) subtypes. METABRIC database and Cox proportional hazard model defined the clinical impact of high RAGE expression in BC patients. Multiple bioinformatics programs identified the main enriched pathways within high RAGE expression BC cohorts. By lentiviral system, TNBC cells were engineered to overexpress RAGE. Western blotting, immunofluorescence, nucleus/cytoplasm fractionation, qRT-PCR, gene silencing and luciferase experiments were performed to identify signal transduction mediators engaged by RAGE upon stimulation with S100A8/A9 in TNBC cells. Proliferation, colony formation and transwell migration assays were carried out to evaluate the growth and migratory capacity of TNBC cells. Statistical analysis was performed by ANOVA and independent t-tests.ResultsWe found a remarkable high expression of S100A8 and S100A9 in BC, particularly in HER2-positive and TNBC, with the latter associated to worst clinical outcomes. In addition, high RAGE expression correlated with a poor overall survival in BC. Next, we determined that the S100A8/A9-RAGE system triggers FAK activation by engaging a cytoskeleton mechanosensing complex in TNBC cells. Through bioinformatics analysis, we identified the Hippo pathway as the most enriched in BC patients expressing high RAGE levels. In accordance with these data, we demonstrated the involvement of S100A8/A9-RAGE-FAK signaling in the control of Hippo/YAP activities, and we established the crucial contribution of RAGE-FAK-YAP circuitry in the growth and migratory effects initiated by S100A8/A9 in TNBC cells.ConclusionsThe present study provides novel mechanistic insights on RAGE actions in TNBC. Moreover, our findings suggest that RAGE-FAK-YAP transduction pathway could be exploited as a druggable system halting the aggressive TNBC subtype.
Erratum: Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for GNAQ-Driven Uveal Melanoma (Clin Cancer Res (2021) 27 (3190–3200) DOI: 10.1158/1078-0432.CCR-20-3363) Justine S. Paradis, Monica Acosta, Robert Saddawi-Konefka, Ayush Kishore, Simone Lubrano, Frederico Gomes, Nadia Arang, Manoela Tiago, Silvia Coma, Xingyu Wu, Kyle Ford, Chi-Ping Day, Glenn Merlino, Prashant Mali, Jonathan A. Pachter, Takami Sato, Andrew E. Aplin, J. Silvio Gutkind Clinical Cancer Research, 2021 Correction: Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for GNAQ-Driven Uveal Melanoma Justine S. Paradis,MonicaAcosta, Robert Saddawi-Konefka, AyushKishore, Simone Lubrano, Frederico Gomes, Nadia Arang, Manoela Tiago, Silvia Coma, Xingyu Wu, Kyle Ford, Chi-Ping Day, Glenn Merlino, Prashant Mali, Jonathan A. Pachter, Takami Sato, Andrew E. Aplin, and J. Silvio Gutkind
Synthetic lethal screens reveal cotargeting FAK and MEK as a multimodal precision therapy for GNAQ-driven uveal melanoma Justine S. Paradis, Monica Acosta, Robert Saddawi-Konefka, Ayush Kishore, Simone Lubrano, Frederico Gomes, Nadia Arang, Manoela Tiago, Silvia Coma, Xingyu Wu, Kyle Ford, Chi-Ping Day, Glenn Merlino, Prashant Mali, Jonathan A. Pachter, Takami Sato, Andrew E. Aplin, J. Silvio Gutkind Clinical Cancer Research, 2021 Purpose:Uveal melanoma is the most common eye cancer in adults. Approximately 50% of patients with uveal melanoma develop metastatic uveal melanoma (mUM) in the liver, even after successful treatment of the primary lesions. mUM is refractory to current chemo- and immune-therapies, and most mUM patients die within a year. Uveal melanoma is characterized by gain-of-function mutations in GNAQ/GNA11, encoding Gαq proteins. We have recently shown that the Gαq–oncogenic signaling circuitry involves a noncanonical pathway distinct from the classical activation of PLCβ and MEK–ERK. GNAQ promotes the activation of YAP1, a key oncogenic driver, through focal adhesion kinase (FAK), thereby identifying FAK as a druggable signaling hub downstream from GNAQ. However, targeted therapies often activate compensatory resistance mechanisms leading to cancer relapse and treatment failure.Experimental Design:We performed a kinome-wide CRISPR-Cas9 sgRNA screen to identify synthetic lethal gene interactions that can be exploited therapeutically. Candidate adaptive resistance mechanisms were investigated by cotargeting strategies in uveal melanoma and mUM in vitro and in vivo experimental systems.Results:sgRNAs targeting the PKC and MEK–ERK signaling pathways were significantly depleted after FAK inhibition, with ERK activation representing a predominant resistance mechanism. Pharmacologic inhibition of MEK and FAK showed remarkable synergistic growth-inhibitory effects in uveal melanoma cells and exerted cytotoxic effects, leading to tumor collapse in uveal melanoma xenograft and liver mUM models in vivo.Conclusions:Coupling the unique genetic landscape of uveal melanoma with the power of unbiased genetic screens, our studies reveal that FAK and MEK–ERK cotargeting may provide a new network-based precision therapeutic strategy for mUM treatment.See related commentary by Harbour, p. 2967
Early modifications of circulating microRNAs levels in metastatic colorectal cancer patients treated with regorafenib Marta Schirripa, Beatrice Borelli, Romina D’Aurizio, Simone Lubrano, Chiara Cremolini, Gemma Zucchelli, Carlotta Antoniotti, Federica Marmorino, Alessandra Anna Prete, Sabina Murgioni, Francesca Bergamo, Vittorina Zagonel, Andrea Tuccoli, Andrea Marranci, Milena Rizzo, Lorena Tedeschi, Letizia Magnoni, Alfredo Falcone, Fotios Loupakis, Laura Poliseno Pharmacogenomics Journal, 2019
Development of a yeast-based system to identify new hBRAFV600E functional interactors Simone Lubrano, Laura Comelli, Chiara Piccirilli, Andrea Marranci, Francesca Dapporto, Elena Tantillo, Federica Gemignani, J. Silvio Gutkind, Alessandra Salvetti, Giovanna Chiorino, Giorgio Cozza, Mario Chiariello, Alvaro Galli, Laura Poliseno, Tiziana Cervelli Oncogene, 2019
The landscape of BRAF transcript and protein variants in human cancer Andrea Marranci, Zhijie Jiang, Marianna Vitiello, Elena Guzzolino, Laura Comelli, Samanta Sarti, Simone Lubrano, Cinzia Franchin, Ileabett Echevarría-Vargas, Andrea Tuccoli, Alberto Mercatanti, Monica Evangelista, Paolo Sportoletti, Giorgio Cozza, Ettore Luzi, Enrico Capobianco, Jessie Villanueva, Giorgio Arrigoni, Giovanni Signore, Silvia Rocchiccioli, Letizia Pitto, Nicholas Tsinoremas, Laura Poliseno Molecular Cancer, 2017
Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells Marianna Vitiello, Andrea Tuccoli, Romina D’Aurizio, Samanta Sarti, Laura Giannecchini, Simone Lubrano, Andrea Marranci, Monica Evangelista, Silvia Peppicelli, Chiara Ippolito, Ivana Barravecchia, Elena Guzzolino, Valentina Montagnani, Michael Gowen, Elisa Mercoledi, Alberto Mercatanti, Laura Comelli, Salvatore Gurrieri, Lawrence W. Wu, Omotayo Ope, Keith Flaherty, Genevieve M. Boland, Marc R. Hammond, Lawrence Kwong, Mario Chiariello, Barbara Stecca, Gao Zhang, Alessandra Salvetti, Debora Angeloni, Letizia Pitto, Lido Calorini, Giovanna Chiorino, Marco Pellegrini, Meenhard Herlyn, Iman Osman, Laura Poliseno Oncotarget, 2017
Identification of BRAF 3'UTR isoforms in melanoma Andrea Marranci, Andrea Tuccoli, Marianna Vitiello, Elisa Mercoledi, Samanta Sarti, Simone Lubrano, Monica Evangelista, Antonella Fogli, Camilo Valdes, Francesco Russo, Massimo Dal Monte, Maria A. Caligo, Marco Pellegrini, Enrico Capobianco, Nicholas Tsinoremas, Laura Poliseno Journal of Investigative Dermatology, 2015
RECENT SCHOLAR PUBLICATIONS
Targeting Hippo/YAP-TEAD increases the antitumor activity of darovasertib in uveal melanoma. RD Cervantes-Villagrana, ES Cardenas Alcoser, K Sato, S Lubrano, ... Cancer Research 86 (7_Supplement), 1837-1837 , 2026 2026
Unraveling Resistance Mechanisms to Gαq Pathway Inhibition in Uveal Melanoma: Insights from Signaling-Activation Library Screening S Lubrano, RD Cervantes-Villagrana, N Arang, ES Cardenas-Alcoser, ... Cancers 18 (1), 74 , 2025 2025
Inhibition of anti-apoptotic BCL2 overcomes adaptive resistance to co-targeting of the protein kinase FAK and MEK in GNAQ-driven uveal melanoma S Lubrano, RD Cervantes-Villagrana, N Arang, A Officer, ... Journal of Biological Chemistry 301 (10) , 2025 2025 Citations: 2
FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma S Lubrano, RD Cervantes-Villagrana, F Faraji, S Ramirez, K Sato, ... Cancer Cell 43 (3), 428-445. e6 , 2025 2025 Citations: 39
The landscape of BRAF transcript and protein variants in human cancer (vol 16, 85 2017) A Marranci, Z Jiang, M Vitiello, E Guzzolino, L Comelli, S Sarti, S Lubrano, ... Molecular cancer 24 (1) , 2025 2025
Correction: The landscape of BRAF transcript and protein variants in human cancer A Marranci, Z Jiang, M Vitiello, E Guzzolino, L Comelli, S Sarti, S Lubrano, ... Molecular Cancer 24, 42 , 2025 2025
A novel combination therapy targeting RAF, MEK and FAK to overcome skin cutaneous melanoma treatment resistance S Lubrano, F Faraji, RD Cervantes-Villagrana, S Ramirez, N Arang, ... Cancer Research 84 (6_Supplement), 4745-4745 , 2024 2024 Citations: 2
High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma N Arang, S Lubrano, M Ceribelli, DC Rigiracciolo, R Saddawi-Konefka, ... Cell Reports Medicine 4 (11) , 2023 2023 Citations: 26
Whole-genome CRISPR screening identifies PI3K/AKT as a downstream component of the oncogenic GNAQ–focal adhesion kinase signaling circuitry N Arang, S Lubrano, DC Rigiracciolo, D Nachmanson, SM Lippman, ... Journal of Biological Chemistry 299 (2), 102866 , 2023 2023 Citations: 21
Focal Adhesion Kinase (FAK)-Hippo/YAP transduction signaling mediates the stimulatory effects exerted by S100A8/A9-RAGE system in triple-negative breast cancer (TNBC) DC Rigiracciolo, N Nohata, R Lappano, F Cirillo, M Talia, ... Journal of Experimental & Clinical Cancer Research 41 (1), 193 , 2022 2022 Citations: 56
Correction: Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for GNAQ -Driven Uveal Melanoma JS Paradis, M Acosta, R Saddawi-Konefka, A Kishore, S Lubrano, ... Clinical Cancer Research 27 (16), 4664-4664 , 2021 2021 Citations: 4
Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for GNAQ -Driven Uveal Melanoma JS Paradis, M Acosta, R Saddawi-Konefka, A Kishore, S Lubrano, ... Clinical Cancer Research 27 (11), 3190-3200 , 2021 2021 Citations: 88
G alpha q controls the Hippo pathway through MOB1 tyrosine phosphorylation by FAK. X Feng, N Arang, DC Rigiracciolo, JS Lee, H Yeerna, Z Wang, S Lubrano, ... MOLECULAR CANCER RESEARCH 18 (8), 32-33 , 2020 2020
Abstract A20: Gαq controls the Hippo pathway through MOB1 tyrosine phosphorylation by FAK X Feng, N Arang, DC Rigiracciolo, JS Lee, H Yeerna, Z Wang, S Lubrano, ... Molecular Cancer Research 18 (8_Supplement), A20-A20 , 2020 2020
Early modifications of circulating microRNAs levels in metastatic colorectal cancer patients treated with regorafenib M Schirripa, B Borelli, R D’Aurizio, S Lubrano, C Cremolini, G Zucchelli, ... The Pharmacogenomics Journal 19 (5), 455-464 , 2019 2019 Citations: 9
A platform of synthetic lethal gene interaction networks reveals that the GNAQ uveal melanoma oncogene controls the hippo pathway through FAK X Feng, N Arang, DC Rigiracciolo, JS Lee, H Yeerna, Z Wang, S Lubrano, ... Cancer cell 35 (3), 457-472. e5 , 2019 2019 Citations: 284
Development of a yeast-based system to identify new hBRAFV600E functional interactors S Lubrano, L Comelli, C Piccirilli, A Marranci, F Dapporto, E Tantillo, ... Oncogene 38 (8), 1355-1366 , 2019 2019 Citations: 12
Targeting FAK inhibits YAP-dependent tumor growth in uveal melanoma X Feng, D Rigiracciolo, JS Lee, H Yeerna, N Arang, S Lubrano, ... Cancer Research 78 (13_Supplement), 968-968 , 2018 2018 Citations: 1
Yeast S. cerevisiae as a tool to study BRAFV600E kinase isoforms S Lubrano Università degli Studi di Siena , 2018 2018
The landscape of BRAF transcript and protein variants in human cancer A Marranci, Z Jiang, M Vitiello, E Guzzolino, L Comelli, S Sarti, S Lubrano, ... Molecular Cancer 16 (1), 85 , 2017 2017 Citations: 44
MOST CITED SCHOLAR PUBLICATIONS
A platform of synthetic lethal gene interaction networks reveals that the GNAQ uveal melanoma oncogene controls the hippo pathway through FAK X Feng, N Arang, DC Rigiracciolo, JS Lee, H Yeerna, Z Wang, S Lubrano, ... Cancer cell 35 (3), 457-472. e5 , 2019 2019 Citations: 284
Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for GNAQ -Driven Uveal Melanoma JS Paradis, M Acosta, R Saddawi-Konefka, A Kishore, S Lubrano, ... Clinical Cancer Research 27 (11), 3190-3200 , 2021 2021 Citations: 88
Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells M Vitiello, A Tuccoli, R D’Aurizio, S Sarti, L Giannecchini, S Lubrano, ... Oncotarget 8 (15), 25395 , 2017 2017 Citations: 83
Focal Adhesion Kinase (FAK)-Hippo/YAP transduction signaling mediates the stimulatory effects exerted by S100A8/A9-RAGE system in triple-negative breast cancer (TNBC) DC Rigiracciolo, N Nohata, R Lappano, F Cirillo, M Talia, ... Journal of Experimental & Clinical Cancer Research 41 (1), 193 , 2022 2022 Citations: 56
The landscape of BRAF transcript and protein variants in human cancer A Marranci, Z Jiang, M Vitiello, E Guzzolino, L Comelli, S Sarti, S Lubrano, ... Molecular Cancer 16 (1), 85 , 2017 2017 Citations: 44
FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma S Lubrano, RD Cervantes-Villagrana, F Faraji, S Ramirez, K Sato, ... Cancer Cell 43 (3), 428-445. e6 , 2025 2025 Citations: 39
High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma N Arang, S Lubrano, M Ceribelli, DC Rigiracciolo, R Saddawi-Konefka, ... Cell Reports Medicine 4 (11) , 2023 2023 Citations: 26
Whole-genome CRISPR screening identifies PI3K/AKT as a downstream component of the oncogenic GNAQ–focal adhesion kinase signaling circuitry N Arang, S Lubrano, DC Rigiracciolo, D Nachmanson, SM Lippman, ... Journal of Biological Chemistry 299 (2), 102866 , 2023 2023 Citations: 21
Identification of BRAF 3′ UTR isoforms in melanoma A Marranci, A Tuccoli, M Vitiello, E Mercoledi, S Sarti, S Lubrano, ... Journal of investigative dermatology 135 (6), 1694-1697 , 2015 2015 Citations: 15
Development of a yeast-based system to identify new hBRAFV600E functional interactors S Lubrano, L Comelli, C Piccirilli, A Marranci, F Dapporto, E Tantillo, ... Oncogene 38 (8), 1355-1366 , 2019 2019 Citations: 12
Early modifications of circulating microRNAs levels in metastatic colorectal cancer patients treated with regorafenib M Schirripa, B Borelli, R D’Aurizio, S Lubrano, C Cremolini, G Zucchelli, ... The Pharmacogenomics Journal 19 (5), 455-464 , 2019 2019 Citations: 9
Correction: Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for GNAQ -Driven Uveal Melanoma JS Paradis, M Acosta, R Saddawi-Konefka, A Kishore, S Lubrano, ... Clinical Cancer Research 27 (16), 4664-4664 , 2021 2021 Citations: 4
Inhibition of anti-apoptotic BCL2 overcomes adaptive resistance to co-targeting of the protein kinase FAK and MEK in GNAQ-driven uveal melanoma S Lubrano, RD Cervantes-Villagrana, N Arang, A Officer, ... Journal of Biological Chemistry 301 (10) , 2025 2025 Citations: 2
A novel combination therapy targeting RAF, MEK and FAK to overcome skin cutaneous melanoma treatment resistance S Lubrano, F Faraji, RD Cervantes-Villagrana, S Ramirez, N Arang, ... Cancer Research 84 (6_Supplement), 4745-4745 , 2024 2024 Citations: 2
Targeting FAK inhibits YAP-dependent tumor growth in uveal melanoma X Feng, D Rigiracciolo, JS Lee, H Yeerna, N Arang, S Lubrano, ... Cancer Research 78 (13_Supplement), 968-968 , 2018 2018 Citations: 1
Targeting Hippo/YAP-TEAD increases the antitumor activity of darovasertib in uveal melanoma. RD Cervantes-Villagrana, ES Cardenas Alcoser, K Sato, S Lubrano, ... Cancer Research 86 (7_Supplement), 1837-1837 , 2026 2026
Unraveling Resistance Mechanisms to Gαq Pathway Inhibition in Uveal Melanoma: Insights from Signaling-Activation Library Screening S Lubrano, RD Cervantes-Villagrana, N Arang, ES Cardenas-Alcoser, ... Cancers 18 (1), 74 , 2025 2025
The landscape of BRAF transcript and protein variants in human cancer (vol 16, 85 2017) A Marranci, Z Jiang, M Vitiello, E Guzzolino, L Comelli, S Sarti, S Lubrano, ... Molecular cancer 24 (1) , 2025 2025
Correction: The landscape of BRAF transcript and protein variants in human cancer A Marranci, Z Jiang, M Vitiello, E Guzzolino, L Comelli, S Sarti, S Lubrano, ... Molecular Cancer 24, 42 , 2025 2025
G alpha q controls the Hippo pathway through MOB1 tyrosine phosphorylation by FAK. X Feng, N Arang, DC Rigiracciolo, JS Lee, H Yeerna, Z Wang, S Lubrano, ... MOLECULAR CANCER RESEARCH 18 (8), 32-33 , 2020 2020
