Blocking The Roads To Resistance In Breast Cancer

From explaining your research to your family, friends or even funding bodies, the ability to communicate your research to the general public is an extremely important skill for scientists. My PhD project is investigating the ways in which breast cancer cells respond and adapt to current treatments and recently I produced an animated video to illustrate my research for the Dublin City University (DCU) Tell It Straight competition. This competition challenged PhD students to communicate their research to a general audience through either a presentation or a video. My video outlines the main aim of my PhD, to investigate drug resistance in breast cancer, and describes what we are doing in the lab to achieve this.

You can view and download a complete copy of my "Tell It Straight" slidedeck here.

Breast cancer is the second most common cancer in women in Ireland with one in ten women developing breast cancer in their lifetime. Thankfully, however, through advances in treatment options, early diagnosis and improved treatment availability, breast cancer mortality is steadily declining. In fact, 80% of women with breast cancer live at least five years after their diagnosis. Research into new, better treatments, and why some cancers don’t respond to current treatment is constantly on-going to further improve the outcome for breast cancer patients.

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Our research in the NICB, led by Dr. Norma O’Donovan and Prof. John Crown, aims to discover new strategies to prevent or overcome resistance to breast cancer drugs. HER2-positive breast cancer overproduces the HER2 protein, a protein located on the surface of the cell that stimulates cancer growth. HER2-positve breast cancer accounts for roughly 20% of all breast cancers. Historically, this type of breast cancer was highly aggressive and patients with this disease had a poor prognosis. However, the advent of HER2-targeted therapies, such as Herceptin and lapatinib, has greatly improved the outcome for these patients. Unfortunately, these HER2-targeted drugs do not work for some patients as cancers can be resistant to these drugs or can develop resistance over the course of treatment.

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Our work aims to find alternative treatments for patients with HER2-positive breast cancer resistant to these drugs. We do this by examining differences in gene activity and levels of specific proteins between HER2-positive breast cancer cells that are sensitive to these drugs and cells that are resistant. We also look for changes in breast cancer cells as they are treated with HER2-targeted therapies and develop resistance. This gives us an insight into what molecules are driving the resistance to treatment. These molecules may act as markers of resistance, which can inform clinicians if a patient would benefit from alternative HER2-targeted therapies, or may be something we could target with other drugs and overcome resistance to HER2-targeted therapies.

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During my PhD, I have been fortunate to work in Dr. Dennis Slamon’s laboratory in University of California, Los Angeles (UCLA), where I examined the sensitivity of a panel of breast cancer cell lines to particular drugs. Dennis Slamon is a pioneer in cancer research. He and his colleagues discovered the link between HER2 and breast cancer. This led to the development of Herceptin, which was one of the first targeted therapies in cancer and revolutionised the treatment of HER2-positive breast cancer. The story of Herceptin’s development is sometimes stranger than fiction, with the project derided in the beginning by funding agencies and fellow oncologists alike. However, Herceptin has become standard of care in HER2-positive breast cancer, and, in fact, the story of Herceptin has been made into a movie, with Harry Connick Jr. as Dennis Slamon.

Our research is part of the Irish Cancer Society’s first collaborative cancer research centre Breast Predict. Breast Predict brings together breast cancer researchers across the country, including laboratory and computational scientists and clinicians. In addition to our research, the Breast Predict team of researchers are developing a national breast cancer biobank that includes tumour and blood samples from almost every breast cancer patient in Ireland, are investigating how breast cancers change over time while on treatment, and whether drugs such as aspirin and statins taken before a patient’s diagnosis can affect their response to treatment.

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3 Responses

  1. Well done Neil. Well written and explained
  2. Well done Neil. Very clear and interesting article.
  3. Really nice and clear. Well done Neil.

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