Research News

For many patients facing cancer, aggressive forms of treatment are part of the reality that comes with the disease. Chemotherapy and radiation, as well as some surgeries, lead to side effects like hair loss, nausea and low blood count—adding complications and difficult dimensions to recovery. But Yogen Saunthararajah, MD, believes that better, less toxic methods of treatment exist, including combination therapy.

A recent article from Dr. Saunthararajah and members of his laboratory, published in Blood Advances, focuses on combination therapy to treat acute myeloid leukemia (AML)—an aggressive but rare cancer that affects bone marrow.

Acute myeloid leukemia and the p53 protein

Some of the most serious forms of AML are those that contain mutations in the gene for p53, which is “a guardian” protein that prevents damaged cells from turning into cancer. These forms of AML resist all forms of treatment. Current treatments for AML include chemotherapy, targeted therapy (which focuses on the genetic changes or mutations that turn healthy cells into cancer cells, including monoclonal antibody therapy) or allogeneic stem cell transplantation. Unfortunately, cures are rare, but risks for serious side effects are high, including risk of infection.

In their research, Dr. Saunthararajah and his team focus on finding nontoxic ways to safely bypass and outsmart AML’s mechanisms of avoiding treatment. In standard chemotherapy treatments, the drugs damage cells and p53 tells them to shut down entirely. But in the case of AMLs with mutations in p53, p53 stops working, which is why drugs do not have much of an effect.

What is combination therapy?

Combination therapy is the use of two or more treatments or medications to treat a single disease. It has gained momentum in cancer treatment in recent years because providers can select drugs that work in different ways. When combined into one dose or given in a specific order, these treatments have the potential to address how cancers evolve over time.

This approach, along with precision oncology, also targets only cancerous cells and preserves healthy cells, as opposed to chemotherapy and radiation.

“Current cancer treatments like chemotherapy and radiation don’t reflect what we find through pathophysiology, or the study of how normal body functions change when someone has a disease like cancer,” Dr. Saunthararajah says. “Aggressive treatments circumvent that and blast everything in a cancerous area, meaning cancerous cells and healthy cells (including skin cells and hair follicles). That’s why many patients experience unrelated, but serious side effects.”

Guided by the Hippocratic Oath

The team identified a combination therapy using drugs already on the market that fight AML by effectively bypassing p53—even when p53 is missing altogether. The treatment only targeted cancer cells, meaning healthy cells (including red blood cells and cells in the skin and hair follicles) were left intact to replicate as they normally would.

Because combination therapy and precision oncology treatments are tailored to each patient based on the individual factors and DNA signature of their cancer, benefits can include fewer (or less severe) side effects, shorter recovery times and better quality of life.

“Patients encountering any kind of cancer deserve a treatment that eliminates only the bad cells and allows the healthy ones to remain,” Dr. Saunthararajah says. “When it comes to those treatments, our goal as Cleveland Clinic physicians and scientists is to fix and heal, not destroy. That is a direct reflection of the Hippocratic Oath that guides our careers: to first do no harm.”