Imperial College London

Dr Elaina Maginn

Faculty of MedicineFaculty of Medicine Centre

Senior Teaching Fellow







Sir Alexander Fleming BuildingSouth Kensington Campus





Publication Type

8 results found

Burmi R, Maginn E, Gabra H, Stronach E, Wasan Het al., 2019, Combined inhibition of the PI3K/mTOR/MEK pathway induces Bim/Mcl-2-regulated apoptosis in pancreatic cancer cells, Cancer Biology and Therapy, Vol: 20, Pages: 21-30, ISSN: 1555-8576

Pancreatic ductal adenocarcinoma (PDAC) progression and chemotherapy insensitivity have been associated with aberrant PI3K/mTOR/MEK signalling. However, cell death responses activated by inhibitors of these pathways can differ – contextually varying with tumour genetic background. Here, we demonstrate that combining the dual PI3K/mTOR inhibitor PF5212384 (PF384) and MEK inhibitor PD325901 (PD901) more effectively induces apoptosis compared with either agent alone, independent of KRAS mutational status in PDAC cell lines. Additionally, a non-caspase dependent decrease in cell viability upon PF384 treatment was observed, and may be attributed to autophagy and G0/G1 cell cycle arrest. Using reverse phase protein arrays, we identify key molecular events associated with the conversion of cytostatic responses (elicited by single inhibitor treatments) into a complete cell death response when PF384 and PD901 are combined. This response was also independent of KRAS mutation, occurring in both BxPC3 (KRAS wildtype) and MIA-PaCa-2 (KRASG12C mutated) cells. In both cell lines, Bim expression increased in response to PF384/PD901 treatment (by 60% and 48%, respectively), while siRNA-mediated silencing of Bim attenuated the apoptosis induced by combination treatment. In parallel, Mcl-1 levels decreased by 36% in BxPC3, and 30% in MIA-PaCa-2 cells. This is consistent with a functional role for Mcl-1, and siRNA-mediated silencing enhanced apoptosis in PF384/PD901-treated MIA-PaCa-2 cells, whilst Mcl-1 overexpression decreased apoptosis induction by 24%. Moreover, a novel role was identified for PDCD4 loss in driving the apoptotic response to PF384/PD901 in BxPC3 and MIA-PaCa-2 cell lines. Overall, our data indicates PF384/PD901 co-treatment activates the same apoptotic mechanism in wild-type or KRAS mutant PDAC cells.

Journal article

Dungl DA, Maginn EN, Stronach EA, 2015, Preventing Damage Limitation: Targeting DNA-PKcs and DNA Double-Strand Break Repair Pathways for Ovarian Cancer Therapy., Frontiers in Oncology, Vol: 5, ISSN: 2234-943X

Platinum-based chemotherapy is the cornerstone of ovarian cancer treatment, and its efficacy is dependent on the generation of DNA damage, with subsequent induction of apoptosis. Inappropriate or aberrant activation of the DNA damage response network is associated with resistance to platinum, and defects in DNA repair pathways play critical roles in determining patient response to chemotherapy. In ovarian cancer, tumor cell defects in homologous recombination - a repair pathway activated in response to double-strand DNA breaks (DSB) - are most commonly associated with platinum-sensitive disease. However, despite initial sensitivity, the emergence of resistance is frequent. Here, we review strategies for directly interfering with DNA repair pathways, with particular focus on direct inhibition of non-homologous end joining (NHEJ), another DSB repair pathway. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a core component of NHEJ and it has shown considerable promise as a chemosensitization target in numerous cancer types, including ovarian cancer where it functions to promote platinum-induced survival signaling, via AKT activation. The development of pharmacological inhibitors of DNA-PKcs is on-going, and clinic-ready agents offer real hope to patients with chemoresistant disease.

Journal article

Maginn EN, de Sousa CH, Wasan HS, Stronach EAet al., 2014, Opportunities for translation: Targeting DNA repair pathways in pancreatic cancer, BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, Vol: 1846, Pages: 45-54, ISSN: 0304-419X

Journal article

Lysaght J, Verma NK, Maginn EN, Ryan JM, Campiani G, Zisterer DM, Williams DC, Browne PV, Lawler MP, McElligott AMet al., 2013, The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells, INTERNATIONAL JOURNAL OF ONCOLOGY, Vol: 42, Pages: 239-246, ISSN: 1019-6439

Journal article

Stronach EA, Chen M, Maginn EN, Agarwal R, Mills GB, Wasan H, Gabra Het al., 2011, DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance, NEOPLASIA, Vol: 13, Pages: 1069-U114, ISSN: 1476-5586

Journal article

Forde JC, Maginn EN, McNamara G, Martin LM, Campiani G, Williams DC, Zisterer D, McElligott AM, Lawler M, Lynch TH, Hollywood D, Marignol Let al., 2011, Microtubule-targeting-compound PBOX-15 radiosensitizes cancer cells in vitro, CANCER BIOLOGY & THERAPY, Vol: 11, Pages: 421-428, ISSN: 1538-4047

Journal article

Maginn EN, Browne PV, Hayden P, Vandenberghe E, MacDonagh B, Evans P, Goodyer M, Tewari P, Campiani G, Butini S, Williams DC, Zisterer DM, Lawler MP, McElligott AMet al., 2011, PBOX-15, a novel microtubule targeting agent, induces apoptosis, upregulates death receptors, and potentiates TRAIL-mediated apoptosis in multiple myeloma cells, BRITISH JOURNAL OF CANCER, Vol: 104, Pages: 281-289, ISSN: 0007-0920

Journal article

McElligott AM, Maginn EN, Greene LM, McGuckin S, Hayat A, Browne PV, Butini S, Campiani G, Catherwood MA, Vandenberghe E, Williams DC, Zisterer DM, Lawler Met al., 2009, The Novel Tubulin-Targeting Agent Pyrrolo-1,5-Benzoxazepine-15 Induces Apoptosis in Poor Prognostic Subgroups of Chronic Lymphocytic Leukemia, CANCER RESEARCH, Vol: 69, Pages: 8366-8375, ISSN: 0008-5472

Journal article

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