Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Last week while I was away at the ASCO GenitoUrinary (GU) symposium in Florida, two interesting findings in cancer science hit the journals, one in breast cancer and the other in glioblastoma, a form of brain cancer.  I thought it would be a good idea to take a quick look at those new publications (see reference links below) over the next couple of days.

Today, we begin with the ZNF703 oncogene in Luminal B breast cancer.

This research is important because it’s the first oncogene to be found in the last 5 years and could be active in up to 1 in 12 breast cancers.   The last active oncogene to be discovered in breast cancer was HER2 and we all know how that worked out!

I always remember Harold Varmus’s pithy keynote lecture at AACR a few ago, where he described how oncogenes work in a very simple to understand way, namely:

“Oncogenes are normal genes that control growth in every living cell, but which, under certain conditions can turn renegade and cancerous.”

The latest research, jointly led by Cancer Research UK Cambridge Research Institute and the British Columbia Cancer Agency in Vancouver, Canada, reports how they looked at gene activity in breast tumour samples (n=1172), as well as looking at breast cancer cells grown in the laboratory.

It’s a elegant study that by a painstaking process of detective work, they were able to sort through the enormous mass of data and eliminate genes, until there was only the ZNF703 gene left within a region on chromosome 8, that was overactive in all the samples tested. Wow.

What is particularly interesting, is that that region of DNA was suspected of harbouring mutant genes twenty years ago, but it is only with modern data gathering and processing tools (ie high-resolution copy number profiling) that the oncogene could be actually be isolated.

Here’s what the scientists concluded:

“Overexpression of ZNF703 in normal human breast epithelial cells enhanced the frequency of in vitro colony-forming cells from luminal progenitors.  Taken together, these data strongly point to ZNF703 as a novel oncogene in Luminal B breast cancer.”

Luminal B histology is common in estrogen receptor-positive (ER+) breast cancers.

Keep an eye on this oncogene, because in the next few years we may well see new targeted drugs emerge from Pharma and Biotech pipelines to target the aberrant activity and by inhibiting the oncogene, switch off the signalling activity driving the cancer.  If that happens, this could well be an important and exciting finding:

“Clinical correlation: ZNF703 amplification is associated with a distinct subtype (Luminal B breast cancer) and with worse clinical outcome in ER+ cancers.  ZNF703 amplification is associated with higher grade and more aggressive tumours, explaining the worse clinical prognosis.”

It’s much easier to design a drug or therapeutic once you have a valid target to aim for and with more specific targeting, comes improved patient outcomes.

Reference:

ResearchBlogging.orgHolland, D., Burleigh, A., Git, A., Goldgraben, M., Perez-Mancera, P., Chin, S., Hurtado, A., Bruna, A., Ali, H., Greenwood, W., Dunning, M., Samarajiwa, S., Menon, S., Rueda, O., Lynch, A., McKinney, S., Ellis, I., Eaves, C., Carroll, J., Curtis, C., Aparicio, S., & Caldas, C. (2011).  ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium EMBO Molecular Medicine DOI: 10.1002/emmm.201100122

3 Responses to “On oncogenes in Luminal B breast cancer”

  1. sgcox

    Its name says it all : it is a zinc-finger trascription factor. Good luck targeting it…

    • maverickny

      I know what you mean – it will be much trickier than HER2 or VEGF, but we’ll see how things progress.

  2. Adam Bristol

    Good point. Several groups have published on transcription factor decoy oligos, e.g., against NFkappaB, but obviously delivery and PK issues are a formindable challenge for this therapeutic modality.

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