Mechanisms of resistance to CDK4/6 inhibitors in triple negative breast cancer

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Published: 12 May 2017
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Dr Uzma Asghar - The Institute of Cancer Research, London, UK

Dr Asghar speaks with ecancer at IMPAKT 2017 about the use of CDK inhibitors against triple negative breast cancer.

She highlights the luminal androgen receptor subtype as especially sensitive, in introduces upcoming trials of combined CDK/PI3K targeted therapies. 

CDK inhibitors have been discussed in ecancer sessions at the St. Gallen 2017 conference, at EONS 10, and at ESMO 2016

Triple negative breast cancer we now know is a heterogeneous group of tumours, there are multiple subgroups. What this research really tries to do is try to stratify response to drugs, specifically CDK4/6 inhibitors, according to their subtype. So in this research I’m particularly focussing on the luminal androgen receptor subtype.

What were the main findings of your research?

We have found a subgroup of triple negative breast cancer, in this case luminal androgen receptor subtype, which is particularly sensitive to CDK4/6 inhibition in preclinical studies. What we have shown is that the sensitivity level is very similar to that that we observe in the ER positive breast cancer models.

What are the potential clinical implications of your findings?

The clinical implications are very exciting. We’ve validated the work in mouse models and now what we have done is we have set up a phase Ib clinical trial which is called PIPA running at the Royal Marsden Hospital and other sites in the UK. What we’re doing is we are now selecting triple negative breast cancer patients with PIK3CA mutations and we are offering them a combination of a CDK4/6 inhibitor and a PI3 kinase inhibitor which reflects the work that we’ve done in the preclinical models.

How do you see treatment for breast cancer changing over the next 10 years?

It’s a very exciting time for breast cancer, there are multiple exciting drugs coming through. There is a lot of excitement and enthusiasm towards trying to look at particularly immunotherapeutic agents in breast cancer. What we’re trying very hard to do in the lab is trying to find particular molecular features or mutational profiles and trying to match them to targeted agents. It looks like it’s going to move towards combination and also what we’re trying to do as a community of oncologists is trying to work out where these combinations fit in the treatment management plan.

What would be your take home message?

The most important message really at this moment in time is that it looks very exciting, CDK4/6 inhibitors, but obviously this needs to be validated in patients. So we can learn a lot from preclinical work and if our experiments are designed well then hopefully we should see some responses in patients.