Biotherapeutics (biologics or biotech drugs) are at the forefront of modern cancer chemotherapy. Examples include the monoclonal antibodies Herceptin ®, Erbitux ® and Perjeta ® , the antibody drug conjugate Kadcyla ®, the immune checkpoint inhibitors Opdivo ® and Yervoy ® and the angiogenesis inhibitor Avastin ®. These therapies are at the forefront of the effort to produce chemotherapy with potent and specific anti-cancer activity but with limited side effects.
The goal of the Cancer Biotherapeutics programme is to fully exploit the potential of these exciting new drugs by generating treatment option rationale for cancers with an unmet clinical need such as triple negative breast cancer, lung cancer and melanoma. Projects utilise cutting-edge laboratory techniques, unique cancer cell line-based resistance models and patient material obtained from the translational component of clinical trials carried out in Ireland.
Our objectives are to:
- Understand the interplay between biotherapeutics and the immune system in order to find new therapeutic targets or potential synergistic combinations with existing or novel chemotherapies.
- Determine the underlying mechanisms of innate and acquired resistance to biotherapeutics that limit the efficacy of these drugs in the clinic.
- Identify patients that will most benefit from biotherapeutics through the analysis of patient-derived material from translational studies.
Current projects are examining:
- The effects of breast and lung cancer-indicated tyrosine kinase inhibitors on the immune response to Herceptin ® and Perjeta ®.
- The role of tumour cell-expressed PD-L1 (an immune checkpoint) in immune cell-mediated cytotoxicity.
- An assessment of the effects of chemotherapy on the plasma proteome of HER2+ breast cancer patients.
- The influence of HER-family mutations on response to HER-family-targeted biotherapeutics (funded by a Roche Postdoctoral Fellowship)
The Cancer Biotherapeutics group are open to collaborations with academia or industry on mutually beneficial projects:
Visit Denis Collins' DCU Business Matchmaker profile to get in touch about collaborations.
Dr Denis Collins (firstname.lastname@example.org)
Mahgoub T, Eustace AJ, Collins DM, O'Donovan N and Crown J. Kinase inhibitor screening identifies CDK4 as a potential therapeutic target for melanoma. International Journal of Oncology (2015 ) 47: 900-908.
Elster N, Collins DM, Toomey S, Crown J, Eustace AJ, Hennessy BT. HER2-family signalling mechanisms, clinical implications and targeting in breast cancer. (Review) Breast Cancer Res Treat (2015) 149:5–15
Collins DM, O’Donovan N, McGowan PM, O’Sullivan F, Duffy MJ and Crown J. Trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in HER-2 non-amplified breast cancer cell lines. Annals of Oncology (2012), 23 (7) 1788-1795.
Dunne G, Breen L, Collins DM, Roche S, Clynes M and O’Connor R. Lapatinib exposure increases P-gp expression. Investigational New Drugs (2011) 29:1284–1293
Tryfonopoulos D, Walsh S, Collins DM, Flanagan L, Quinn C, Corkery B; McDermott EW, Evoy D, Pierce A, O'Donovan N, Crown J, Duffy MJ. Src: a potential target for the treatment of triple-negative breast cancer. Annals of Oncology (2011) 22 (10): 2234-2240
Brougham DF, Ivanova G, Gottschalk M, Collins DM, Eustace AJ, O'Connor R, Havel J
Artificial neural networks for classification in metabolomic studies of whole cells using 1H nuclear magnetic resonance. Journal of Biomedicine Biotechnology (2011) Volume: 2011, Issue: 2000, Pages: 158094
Walsh N, Kennedy S, Larkin AM, Tryfonopoulos D, Eustace AJ, Mahgoub T, Conway C, Oglesby I, Collins D, Ballot J, Ooi WS, Gullo G, Clynes M, Crown J, O'Driscoll L. Membrane transport proteins in human melanoma: associations with tumour aggressiveness and metastasis. British Journal of Cancer (2010) Mar 30;102(7):1157-62.
Collins DM, Crown J, O’Donovan N, O’Sullivan F, O’Driscoll L, Clynes M and O’Connor R. Tyrosine kinase inhibitors potentiate the cytotoxicity of MDR-substrate anticancer agents independent of growth factor receptor status in lung cancer cell lines. Investigational New Drugs (2010), 28 (4) 433-444.