Pakistani, UK researchers make blood cancer treatment discovery

KARACHI: A recent study in the Neoplasia journal by faculty at Aga Khan University (AKU)’s Centre 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.

As per a press release, 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.

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, Philadelphia-positive Acute Lymphoblastic Leukaemia (Ph+ALL), were treatable, almost one-third of Ph+ALL patients had become impossible to treat due to developing resistance to current treatments.

Until now, the mechanism for this type of resistance had remained unknown.

Cells in our body communicate using chemical signals. These chemical signals, which were proteins or other molecules, were 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 does not switch off in treatment-resistant Ph+ALL,” stated Dr Afsar Mian, an assistant professor at CRM.

“Blocking this pathway will 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 had investigated a number of signalling pathways and his past work and experience led him to partner with a leading researcher in the field, Professor 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.

“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 included 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.