KARACHI: Nearly one in three people living with an untreatable form of blood cancer can now look forward to the development of new therapies for their disease after researchers identified a mechanism that makes existing treatments ineffective and how this can be overcome.

Leukaemia is one of the three major types of blood cancer. While most cases of leukaemia, including a subtype of the disease, Philadelphia-positive Acute Lymphoblastic Leukaemia, 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 signalling pathway that, when targeted, can kill, or suppress the growth of resistant leukemic cancerous cells.

Cells in human 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 do not stop, as it happens in some cases, they can cause serious health problems such as cancer.

“Our study detected a signalling pathway which is switched on and doesn’t switch off in treatment-resistant Philadelphia-positive Acute Lymphoblastic Leukemia, Ph+ALL,” said 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 signalling pathways and his past work and experience led him to partner with a leading researcher in the field, Prof Oliver Ottmann of Cardiff University, UK, 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.

Published in Dawn, October 23rd, 2021