Even a couple of decades back targeted therapy for chronic myeloid leukemia was unknown. With the discovery of the chromosomal abnormality that leads to translocation of one portion of the chromosome 9 onto chromosome 22 and vice versa the BCR-ABL gene was found. This is an oncogene or a gene that causes cancer. This gene was found to code for an abnormal protein called the BCR-ABL tyrosine kinase.
This abnormal protein leads to the growth and development of the cancer cells in CML. It was research that found drugs like Imatinib that could successfully inhibit or block the tyrosine kinase and selectively kill the cancer cells. This significantly slows the growth and progression of cancer cells.
Scope for research
Because of the potential for growth and unique characteristics of CML, it has tremendous scope for research.
Clinical trials on CML
Every new drug or treatment regimen undergoes a series of studies called “clinical trials” before it becomes part of standard therapy and is recommended by National and International guidelines.
There are several clinical trials that are being conducted on CML. Clinical trials are highly ethical and controlled research studies that are done with patients who volunteer for them. These help in development of promising new treatments or procedures in medical science.
There are several clinical trials for newly diagnosed patients as well as for those with advanced phase disease or who are intolerant of or resistant to their current treatment.
Patients with CML may take part in such clinical trials. They can talk to their doctors as well as search on websites like www.cancer.org/clinicaltrials and get a list of current clinical trials by calling the National Cancer Institute's Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).
Drugs in development in CML
There are several drugs that are being developed in CML. Some of these include:-
- New tyrosine kinase inhibitors - Ponatinib (AP24534) and Bosutinib. Ponatinib has shown promising clinical activity against mutations in DNA that lead to resistance of the cancer to the initial tyrosine kinase inhibitors like Imatinob, Nilotinib and Dasatinib. Ponatinib in initial trials has shown to be well tolerated with some side effects like rash, headache, joint pain, fatigue etc. Bosutinib has shown efficacy in patients who have failed after treatment with one or more tyrosine kinase inhibitors.
- Inhibitors of a protein called “smoothened” (SMO) used in combination with BCR-ABL tyrosine kinase inhibitors.
- Vaccines for CML – Several vaccine approaches that would prevent CML are being researched. As targets the proteins on the surface of CML cells are chosen and are being researched.
- Modified stem cell transplantation research – A modified form of stem cell transplantation is being researched as well. This would help patients who do not respond to other treatments.