Developing a Targeted Therapy for Breast Cancer
Dr. James Brown is a Lecturer and Principal Investigator at the National University of Ireland Galway. In 2018, he shared with us a scientific discovery that inspired his own research and received a travel award to attend a conference of his choice. He chose to attend the European Association for Cancer Research (EACR) conference on Making it Personal: Cancer Precision Medicine.
The discoveries of ER/PR and Her2 receptors on breast cancer have not only allowed breast cancer to be sub-typed, but also provide among the first targets for truly personalized medicine (with either endocrine or Herceptin), which very quickly led to improved patient survival. A perfect example of research translating into real clinical impacts.
Dr. James Brown, National University of Ireland Galway
Science moves forward when you share it with the world, so we asked Dr. James Brown to share some information on his own research and on his experience at Making it Personal: Cancer Precision Medicine conference.
The Research: Developing a Precise Inhibitor for Breast Cancer Treatment
Can you tell us about your research?
Our research aim is the development and validation of targeted inhibitors for the individualised treatment of cancer. KATs (lysine acetyltransferases, also known as histone acetyltransferases: HATs) are involved in transcriptional regulation, in maintaining genome stability, and are dysregulated in many cancer types. Tip60 is a KAT (arguably the most important one) with roles in transcriptional regulation and, importantly, as the master regulator of the DNA double strand break response. The complete loss of Tip60 is lethal (in somatic cells and is essential for embryonic development), making it difficult to fully study all of its roles. A significant loss of Tip60 expression (mRNA and protein) is seen in many cancers, including breast. We designed a KATi to specifically inhibit Tip60 acetyltransferase activity, allowing us to precisely and tuneably inhibit Tip60 at specific times and to specific extents.
Our work (Gao et al, Sci Rep. 2014) demonstrated that breast cancer is sensitive to our KATi TH1834, specifically inducing cell death in breast cancer cells (and not non-tumourigenic cells). As such, we are further evaluating our KATi as a new targeted treatment for breast cancer. We are also using our KATi to investigate new molecular roles for Tip60 in DNA damage signalling, and in cancer.
EACR conference on Making it Personal: Cancer Precision Medicine 2018, Bergamo, Italy
Why did you choose to attend the 2018 EACR conference?
I chose the EACR Making it Personal: Cancer Precision Medicine conference as previous EACR conferences were exceptional. They are the perfect size. The conference allows delegates to easily meet, discuss research with the speakers, and see the latest (often unpublished) work. The Cancer Precision Medicine conference had a great list of invited speakers, covering a range of topics, including novel strategies and techniques for stratifying patient groups, and the use of new targeted treatments to improve patient outcomes.
Can you tell us about your favorite presentations at the conference?
One of my highlights of the conference was the presentation and panel discussion by Professor Eytan Ruppin (NCI, USA). His work on genetic interactions in cancer, synthetic lethality, and synthetic rescue is exciting and influential. He is also a very engaging and entertaining speaker, whose great passion and enthusiasm for his work come across to the audience.
I also found the presentation by Professor Silvia Formenti (Weill Cornell Medical College, USA) on combining immune manipulation with DNA damage to improve treatment responses very exciting and will influence my thinking on my own research.
How has attending this conference inspired you or affected your current research?
Tip60 has a known role in regulating T cells (Bin et al, Sci Immunol. 2017), functioning through FOXP3 (the master transcription factor of regulatory T cells). Presentations at the conference gave me new ideas about exploring additional effects of our KATi on different elements of the immune system, and the immune response to current therapeutics. In addition, I now would like to further investigate the potential of our KATi and how different genetic backgrounds may influence responses to our KATi.
A Word of Advice: Be Fearless
What advice do you have for the next generation of scientists?
Don’t be afraid to approach well known or senior investigators, particularly ones you might like to collaborate with, to discuss your work. They will often be more supportive and encouraging than you might have expected.