Targeted therapies - look how far we’ve come
24th March 2022
Isabelle Sotheran, Senior Medical Writer

Targeted therapies - look how far we’ve come

Cancer treatment has come a long way in the last few decades thanks to a greater understanding of the molecular events underpinning cancer development and the development of targeted therapies, which, as the name would suggest, target specific molecular or genetic differences between cancer cells and healthy cells.1

A great example of the success of targeted therapies, is in chronic myeloid leukaemia (CML), which is a myeloproliferative disorder, or cancer of the white blood cells. Back in the 1990s, scientists in Philadelphia identified a specific genetic fusion in CML cancer cells that led to the formation of a new gene called BCR-ABL1.2 This gene codes for a tyrosine kinase protein to be expressed at much higher levels than other tyrosine kinases in normal cells. This drives rapid cell proliferation and cancer growth.2

High-throughput screening identified a compound which could specifically bind to and inhibit this BCR-ABL1 – a tyrosine kinase inhibitor (TKI).3 This compound was developed into a cancer therapy called imatinib, which revolutionised CML treatment once approved in the early 2000s.3

Since the discovery and approval of imatinib, there have been many more TKIs developed, all with largely similar mechanisms of action, and we have seen the 5-year survival rate for CML increase from 32.3% in the 1990 to 73.8% in 2013 – a huge win in the fight against cancer!4

But, as with all targeted therapies, cancer finds a way to fight back, mutating and developing resistance to treatments and leaving many patients resistant to therapy. This is no different for CML; mutations in the BCR-ABL1 gene cause structural changes in the protein which prevent the binding and subsequent inhibition of the tyrosine kinase allowing the disease to progress unmanaged.5 Many patients cycle through TKIs and different combinations of these treatments due to resistance or unmanageable side effects. 

But now, fast forward into 2022 and we have a new treatment in the wings for CML: asciminib – a STAMP inhibitor, which stands for Specifically Targeting the ABL Myristoyl Pocket inhibitor.6 It has a novel mechanism of action, binding to the myristate pocket of BCR-ABL1, acting as an allosteric modulator to inhibit activity of the kinase.5,6 This means that it binds to the BCR-ABL1 protein at a different site to the substrate-binding pocket and changes the binding site, preventing the protein’s activity.6

Asciminib is currently pending NICE approval as a 3rd-line CML therapy, bringing a new option to the table for patients with resistance or intolerance to TKI therapy.7

In other good new, last month it was given a positive scientific opinion by the Medicine’s and Healthcare products Regulatory Authority (MHRA) under the Early Access to Medicines Scheme (EAMS), which allows patients with CML to gain access to the drug ahead of marketing authorisation.8

The EAMS is a vital scheme that gives patients with life-threatening or severely debilitating conditions access to medicines that do not yet have marketing authorisation. The scheme was launched in 2014 and has already provided access to life-saving medication for many patients who would otherwise have had to wait months, or maybe even years, for treatment. The most notable example of the EAMS at work was the use of the first COVID-19 medicine, remdesivir, to shorten hospital stays. 9

Oncology is a very complex therapy area which is always evolving as we learn more about cancer and find new ways to target it. CML is considered a success story of oncology due to the huge improvements in patient outcomes, however, despite this, there is still an unmet need for additional therapy options for patients and for innovation and thinking outside the box. The combined contribution of key stakeholders across the drug development process has helped provide hope to those patients for whom current treatment options aren't enough.

  1. Pucci C, et al. eCancer 2019;13:961.
  2. Druker B, Lydon N. J Clin Invest 2000;105:1.
  3. Deininger M, et al. Blood 2005;105:7.
  4. Seer Cancer Stat Facts: Leukemia — Chronic Myeloid Leukemia (CML). Available at (Accessed March 2021)
  5. Schoepfer J, et al. J Med Chem 2018;61:8120­–8135. 
  6. Rea D, et al. Blood 2021;138:21.
  7. NICE: Asciminib for treating chronic myeloid leukaemia after 2 or more tyrosine kinase inhibitors [ID3813]. Available at: March 2021)
  8. Asciminib EAMS. Asciminib in the treatment of chronic myeloid leukaemia. Available at: (Accessed March 2021)
  9. UK EAMS press release. 2 February 2022. Available at: (Accessed March 2021)