Cell cycle drugs

Question 1

Palbociclib

Answer 1

approved UK 2017

HR-/HER2-negative breast cancer, where overexpression of cyclin D is commonly seen

Question 2

APR-246

Answer 2

FDA has recently granted breakthrough therapy designation for the treatment of patients with TP53 mutant myelodysplastic syndromes (MDS) with the comvination of APR-246 and azacitidine and the randomised phase III study of APR-246 and azacitidine versus azacitidine is ongoing in MDS patients. Trial published May 2021. 44% pts in complete remission.

Question 3

Bay

Answer 3

Mps1 inhibitor entered a Phase 1 clinical trial in combination with intravenous paclitaxel (Taxol), with the aim to strongly increase chromosomal segregation errors.
Dec 2021 results - combination associated with considerable toxicity (bone marrow toxicity) and limited therapeutic window

Question 4

AMG510

Answer 4

an inhibitor targeting KRAS G12C for non-small cell lung cancer. A phase I trial published in May 2019 showed response rates of around 50%. Although this is promising, further research is needed to evaluate drug resistance, evaluate drug efficacy and target other RAS mutants