TAT 2018: Understanding the Mecanism of Resistance to CDK4/6 Inhibitors

Speaker: Violetta Serra

Most of oestrogen receptor positive metastatic breast cancer patients are receiving CDK4/6 inhibitors, now approved for first-line treatment. Violetta Serra explains that the challenge is now to identify resistance to these drugs in order to establish potential second line treatments.

Recent data about the clinical resistance mechanisms to CDK4/6 inhibitors show the acquisition of EGFR alterations and RB1 mutations which are associated to the progression of the disease in this pathway.

We know that PIK3CA mutations are truncal and may be already identified in the primary tumour, but other alterations like oestrogen receptor mutation or RB1 mutations are acquired after resistance. We need to determine a molecular MAP of the tumour at progression.

Luckily we have other strategies to sequence the tumours. We can use liquid biopsy to look at circulating tumour DNA to try to identify alterations in plasma.