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Articles by Andrew E. Aplin
S-phase targeted treatment triggers caspase-dependent lytic immunogenic cell death with pyroptotic features in cancers
Abstract Immunogenic cell death (ICD) is a type of cell death that can enhance anti-tumour immune responses of chemotherapies and targeted therapies by releasing DAMPs and cytokines that activate dendritic cells and T cells, thereby engaging the patient’s immune system to combat the cancer. Pyroptosis and necroptosis are strongly immunogenic because they release DAMPs and inflammatory signals through pore-forming proteins, whereas apoptosis can be tolerogenic.
FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma
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Keywords avutometinib signal transduction targeted therapies FAK resistance BRAF MEK melanoma MAPK signaling immunotherapy Get full text access Log in, subscribe or purchase for full access. References 1. Siegel, R.L. ∙ Giaquinto, A.N. ∙ Jemal, A. Cancer statistics, 2024 CA Cancer J. Clin. 2024; 74:12-49 2. Davies, H. ∙ Bignell, G.R. ∙ Cox, C. ... Mutations of the BRAF gene in human cancer Nature. 2002; 417:949-954 3. Lavoie, H. ∙ Therrien, M. Regulation of RAF protein kinases in ERK signalling Nat. Rev. Mol.
By Simone Lubrano, Rodolfo Daniel Cervantes-Villagrana, Farhoud Faraji, Sydney I. Ramirez, Kuniaki Sato, Sendi R. Adame-Garcia, Adam Officer, Nadia Arang, Damiano C. Rigiracciolo, Claudia Martini, Yiyu Wang, Fleur M. Ferguson, Antonietta Bacchiocchi, Ruth Halaban, Sílvia Puigarnau Coma, Sheri Holmen, Jonathan A. Pachter, Andrew E. Aplin, J. Silvio Gutkind
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Cell Press
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Meeting Report From the 2023 Cure Ocular Melanoma (CURE OM) Global Science Meeting, Philadelphia, PA, November 2023
The 2023 Cure Ocular Melanoma (CURE OM) Global Science Meeting was held in Philadelphia on November 6, 2023. The meeting served as an international research forum about uveal melanoma for investigators, researchers, industry partners, and patients. 1 Introduction In conjunction with the 20th International Congress of the Society for Melanoma Research, the 2023 Cure Ocular Melanoma (CURE OM) Global Science Meeting was held in Philadelphia, PA on November 6, 2023.
Mcl-1 mediates intrinsic resistance to RAF inhibitors in mutant BRAF papillary thyroid carcinoma - Cell Death Discovery
Abstract Papillary thyroid carcinoma (PTC) is the most frequent form of thyroid cancer. PTC commonly presents with mutations of the serine/threonine kinase BRAF (BRAFV600E), which drive ERK1/2 pathway activation to support growth and suppress apoptosis. PTC patients often undergo surgical resection; however, since the average age of PTC patients is under 50, adverse effects associated with prolonged maintenance therapy following total thyroidectomy are a concern.
20th Anniversary of the Society for Melanoma Research: Celebrating two decades of progress in melanoma research
Dear Colleagues, It is with great enthusiasm that we look forward to welcoming you to Philadelphia to celebrate a milestone for the melanoma research community: the 20th Anniversary of the Society for Melanoma Research (SMR). The SMR was established in 2003 during the First International Melanoma Research Congress in Philadelphia. Meenhard Herlyn and Kate O'Neill were the driving force behind the inaugural SMR congress.
MacroH2A restricts inflammatory gene expression in melanoma cancer-associated fibroblasts by coordinating chromatin looping - Nature Cell Biology
Abstract MacroH2A has established tumour suppressive functions in melanoma and other cancers, but an unappreciated role in the tumour microenvironment. Using an autochthonous, immunocompetent mouse model of melanoma, we demonstrate that mice devoid of macroH2A variants exhibit increased tumour burden compared with wild-type counterparts.
Site matters in metastatic melanoma
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From the Community to the Bench and Back Again: The Value of Patient and Community Engagement in Cancer Research
Science in Society Amy E. Leader and Andrew E. Aplin DOI: 10.1158/2159-8290.CD-21-0693 Published September 2021 This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below. Abstract Summary: Currently, patients and community members have more frequent interaction with clinical and population scientists than basic scientists, leading to gaps in their engagement across the cancer research continuum.
Roles of the BAP1 Tumor Suppressor in Cell Metabolism
Review Anna Han, Timothy J. Purwin and Andrew E. Aplin DOI: 10.1158/0008-5472.CAN-20-3430 Published June 2021 This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below. Abstract BRCA1-associated protein 1 (BAP1) is emerging as an intensively studied cancer-associated gene. Germline mutations in BAP1 lead to a cancer syndrome, and somatic loss is found in several cancer types.
Sidney Kimmel Cancer Center - Jefferson Health names deputy director
June 02, 2021 1 min read Save ADD TOPIC TO EMAIL ALERTS Receive an email when new articles are posted on Please provide your email address to receive an email when new articles are posted on . We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com. Andrew E. Aplin, PhD, has been appointed deputy director for scientific strategy at Sidney Kimmel Cancer Center — Jefferson Health.
Roles of the BAP1 Tumor Suppressor in Cell Metabolism
Review Anna Han, Timothy J. Purwin and Andrew E. Aplin DOI: 10.1158/0008-5472.CAN-20-3430 Abstract BRCA1-associated protein 1 (BAP1) is emerging as an intensively studied cancer-associated gene. Germline mutations in BAP1 lead to a cancer syndrome, and somatic loss is found in several cancer types. BAP1 encodes a deubiquitinase enzyme, which plays key roles in cell-cycle regulation, cell death, and differentiation.
PROactively TACkling CDK4/6 therapy resistance
Small-molecule kinase inhibitors have made major advances in cancer therapy, but their efficacy remains limited by intrinsic and acquired resistance. The expression and thermostability of the kinase CDK6 are now shown to mediate intrinsic resistance to CDK4/6 inhibitors and degraders across cancer types. Fig. 1: Inhibitor- and PROTAC-mediated blockade of CDK4/6. References 1. Subbiah, V., Baik, C. & Kirkwood, J. M. Trends Cancer 6, 797–810 (2020). CAS Article Google Scholar 2. Goel, S., DeCristo, M.
Roles of the BAP1 Tumor Suppressor in Cell Metabolism
Review Anna Han, Timothy J. Purwin and Andrew E. Aplin DOI: 10.1158/0008-5472.CAN-20-3430 Abstract BRCA1-associated protein 1 (BAP1) is emerging as an intensively studied cancer-associated gene. Germline mutations in BAP1 lead to a cancer syndrome, and somatic loss is found in several cancer types. BAP1 encodes a deubiquitinase enzyme, which plays key roles in cell-cycle regulation, cell death, and differentiation.
Fueling the Fire: Inflammatory Forms of Cell Death and Implications for Cancer Immunotherapy
Reviews Sheera R. Rosenbaum, Nicole A. Wilski and Andrew E. Aplin DOI: 10.1158/2159-8290.CD-20-0805 Published February 2021 This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below. Abstract Unleashing the immune system with immune checkpoint inhibitors (ICI) has significantly improved overall survival for subsets of patients with stage III/IV cancer.
Combined SHPments: An Effective Therapeutic Strategy for MPNST
Cancer Research Highlights Andrew E. Aplin and Claudia Capparelli DOI: 10.1158/0008-5472.CAN-20-3834 Published January 2021 This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below. Abstract Targeted therapies have provided the foundation for many advances in the treatment options for patients with late-stage cancer, however, adaptive and compensatory responses frequently limit their efficacy.
Roles of the BAP1 tumor suppressor in cell metabolism
Review Anna Han, Timothy J. Purwin and Andrew E. Aplin DOI: 10.1158/0008-5472.CAN-20-3430 Abstract BRCA1-associated protein 1 (BAP1) is emerging as an intensively studied cancer-associated gene. Germline mutations in BAP1 lead to a cancer syndrome, and somatic loss is found in several cancer types. BAP1 encodes a deubiquitinase enzyme, which plays key roles in cell cycle regulation, cell death, and differentiation.
Metabolic Alterations and Therapeutic Opportunities in Rare Forms of Melanoma
Rabbie R. et al. Melanoma subtypes: genomic profiles, prognostic molecular markers and therapeutic possibilities. J. Pathol. 2019; 247: 539-551 Alicea G.M. Rebecca V.W. Emerging strategies to treat rare and intractable subtypes of melanoma. Pigment Cell Melanoma Res. 2021; 34: 44-58 Chua V. et al. The latest on uveal melanoma research and clinical trials: updates from the Cure Ocular Melanoma (CURE OM) Science Meeting (2019). Clin. Cancer Res. 2021; 27: 28-33 Faubert B. et al.
Melanoma Research Foundation presents Humanitarian Award
June 04, 2020 1 min read ADD TOPIC TO EMAIL ALERTS Receive an email when new articles are posted on Please provide your email address to receive an email when new articles are posted on . We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com. Melanoma Research Foundation will present its Humanitarian Award to Andrew E. Aplin, PhD.
m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade
Abstract Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N6-methyladenosine (m6A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway.
Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation
Abstract Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells.
US-style fracking success far from guaranteed on British soil
Britain’s energy-hungry population is highly dependent on oil and gas, which powers around two thirds of the UK’s energy needs. The Department of Energy and Climate Change (DECC) projects that by 2030, this proportion will not have changed much. But the source of that oil and gas is changing, and changing fast. In 2005, the UK was self-sufficient in both oil and gas, but now imports about one third of both.
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