Nearly 1 in 3 people living with an untreatable form of blood cancer can now look forward to the development of new therapies for their disease after researchers discovered a mechanism that makes existing treatments ineffective and how this can be overcome.
Leukemia is one of the three major types of blood cancer. While most cases of leukemia, including a subtype of the disease, Philadelphia-positive Acute Lymphoblastic Leukemia, Ph+ALL, are treatable, almost one-third of Ph+ALL patients have become impossible to treat due to developing resistance to current treatments. Until now, the mechanism for this type of resistance has remained unknown. A recent study in the Neoplasia journal by faculty at Aga Khan University's Center for Regenerative Medicine (CRM) and Cardiff University has pinpointed a series of cascading chemical reactions or a signaling pathway that, when targeted, can kill, or suppress the growth of resistant leukemic cancerous cells.
Cells in our body communicate using chemical signals. These chemical signals, which are proteins or other molecules, are meant to facilitate different functions of cells. These signals usually stop after serving their purpose. If they don't stop, as it happens in some cases, they can cause serious health problems such as cancer.
“Our study detected a signaling pathway which is switched on and doesn't switch off in treatment-resistant Philadelphia-positive Acute Lymphoblastic Leukemia, Ph+ALL," says Dr Afsar Mian, an assistant professor at CRM. “Blocking this pathway would prevent a protein from activating another protein thereby preventing the development of resistance in cancer cells and ultimately their growth and spread."
Over the course of his career, Dr Mian has investigated a number of signaling pathways and his past work and experience led him to partner with a leading researcher in the field, Professor Oliver Ottmann of Cardiff University, United Kingdom, to investigate the AKT/mTOR pathway.
In this study, researchers used cell lines from a child and an adult with Ph+ALL. Drug resistance was induced in the child's sample while the adult's sample was already resistant to treatment. In both cases, they found the AKT/mTOR pathway to be responsible for promoting drug resistance and noticed how a specific chemical compound acted as a 'brake' on the functioning of the pathway, halting the growth of cancerous cells.
“The first step to discovering a new cancer drug is to know the mechanisms underlying the development, progression and resistance of a specific cancer," said Dr Mian. “We now hope that our research will help us develop more effective and novel targeted treatments."
Stem cell researchers at the CRM are already in the process of developing new therapies for Ph+ALL.
Contributors to the study include Professor El-Nasir Lalani, founding director of CRM and the Khatija and Mohan Manji Dhrolia Endowed Chair in Stem Cell Biology and Regenerative Medicine, and Usva Zafar and Syed Muhammad Areeb Ahmed, research associates at CRM.