One of the stark realities of cancer research is that many of the drugs, treatments and tests currently being developed won’t be available to patients for years. Some researchers, however, are placing an emphasis on improving treatments for today’s patients. Dr. Faisal Khan is among those researchers.
Khan is an associate professor in medicine at the University of Calgary, where he is the Barb Ibbotson Alberta Children’s Hospital Foundation Chair of Pediatric Hematology. He is also the director of the Molecular Hematology Lab and associate clinical director of the Histocompatibility and Immunogenetic Lab with Alberta Public Laboratories (south).
At the U of C, Khan is the director of the Hematology Translational Lab, where his team studies hematologic malignancies — a group of cancers affecting the cells that make up blood. The lab’s specific focus is developing better treatments and tests for lymphomas and various types of leukemia, which is a type of blood cancer.
“It’s not just research that’s going to benefit patients 20 years from now,” says Khan. “The entire goal is to build a translational research program that can have both short-term and long-term impacts.”
Khan and his research team recently took a big step toward reaching their goal of helping patients as quickly as possible. In September 2017, the Alberta College of Physicians and Surgeons accredited their lab to perform testing for clinical interventions in Alberta. The clinical accreditation means research labs, like Khan’s, can use newly discovered methods and biomarkers as clinical tests, within just three to six months, compared to a standard of one to three years for other labs.
“It means that the biomarkers and tests we develop in the research lab are able to reach patients much faster compared to before, when we had to transfer those tests to a clinical lab for clinical validation,” says Khan.
The bench-to-bedside approach is already improving the treatment of certain cancers in the province. In 2017, Khan’s lab developed a new method of sequencing the myeloid tumours of those suffering from acute myeloid leukemia (AML). This blood and bone marrow cancer is the hematologic malignancy with the worst prognosis. Roughly 200 Albertans are diagnosed with AML each year and the two-year survival rate is just 35 per cent.
Khan’s lab’s new sequencing method is now used to evaluate treatment options for every new AML patient in the province. Armed with precise information on the makeup of the tumour, clinicians are better able to determine whether a patient should receive a cell transplant, chemotherapy, or be placed in clinical trials that target specific mutations.
Khan and his team are also investigating the prevention of relapse for AML patients. Thanks to donor support from the Alberta Cancer Foundation, Khan is developing and validating a diagnostic tool to accurately predict the risk of relapse, enabling medical teams to select high-risk patients that may benefit from protective treatment to decrease relapse rates.
Matching patients with the best treatment options is central to Khan’s research program. Another one of his team’s studies focuses on improving the system that matches cell-transplant donors and patients of different hematological malignancies. Around 90 to 110 stem cell transplants are performed each year in Alberta, with donors and recipients being matched using a set of genes known as human leukocyte antigens (HLAs).
HLAs are protein-markers that the immune system uses to differentiate self from non-self. Right now, patients are matched with donors that are a 10 out of 10 HLA match, meaning that the doctor currently looks for 10 HLA markers (5 HLA genes with two copies of each gene) and selects a donor who has the same set of 10 HLA genes as the patient. Despite the 10/10 matches, complications still occur fairly often. For example, 40 to 50 per cent of patients develop a potentially fatal complication known as graft-vs-host disease, while a further 20 per cent suffer a relapse of the cancer.
In an attempt to improve these outcomes, Khan and his team have identified additional immunogenetic factors that, if present in donors, or matched between donor and recipient, will then lead to less adverse outcomes. Donors are still 10/10 HLA matches, but now they are also matched on additional immunogenetic criteria to help reduce complications and ideally lead to more successful transplants.
The study, which is specific to Alberta, is still in the early phases, but initial results show that identifying these specific immunogenetic factors in the donor and recipient, in combination with HLA matching, greatly improves the chances of the host body accepting the cell transplant without complication. A multi-centre study is planned to confirm the results.
“If it turns out to be true, we can change the donor selection algorithm, where a donor is not just selected based on human leukocyte antigen match, but also based on these other immunogenetic factors so that we can prevent complications after transplant,” says Khan.
With new ways to understand the specific makeup of tumours and the genetic factors that lead to treatment success, in addition to biomarkers that can provide an early and accurate prediction of relapse, Khan is helping push survival rates in the right direction, both in the future and today.