A Nontoxic Pill to Replace Chemotherapy? It’s Possible
A cure for cancer: It’s the holy grail of medical challenges, and researchers want nothing more than to finally crack the code.
It’s widely known that chemotherapy (the use of toxic drugs to treat cancer) has debilitating side effects. Chemotherapy drugs cannot differentiate between cancer cells and normal cells – so they destroy both.
Patients undergoing chemotherapy can become weak and ill. Even when cancer is cured, the treatment itself may have lasting side effects.
But what if a pill could replace chemotherapy? What if that pill were nontoxic, had minimal to no side effects and carried a success rate near 100 percent?
It may sound like science fiction, but an oral medication as routine as a blood pressure pill could be standard treatment for cancer in the near future.
Yogen Saunthararajah, MD, a hematologist at Cleveland Clinic’s Taussig Cancer Institute, is the researcher behind three clinical trials launched this past spring to test the effectiveness of a cancer-fighting pill.
“This is about more than a drug,” Dr. Saunthararajah says. “This represents a new modality in treatment – it’s a conceptual shift, a completely new approach.”
Back to basics
While everyone seems to be talking about precision medicine and developing different treatments for different cancers, Dr. Saunthararajah is taking a broader approach.
“Cancers are different like human beings are different,” he says. “Of course, we are all unique! But we share over 99 percent of our DNA with one another. Our cores are the same, and the cores of cancers are the same, despite superficial differences.”
When it comes to cancer, “the only difference that really matters is this: a distinction between cancer and normal cells that we can use to stop one and not the other.”
“The heart of all biology is the capacity to self-replicate, to reproduce,” he says. “So, we look at the engine of reproduction for differences. And it all comes down to the process of cell specialization.”
A balancing act
Specialization, also called “differentiation,” is a standard phase of any normal cell’s lifecycle. But cancer cells are not normal cells.
“Cancer cells started on this journey to become a specialized something, but they couldn’t get there,” Dr. Saunthararajah says. “They keep trying, but they hit a wall. And we have to ask, ‘why?’
“Well, every cell has two kinds of enzymes – positive and negative. There has to be a balance of both within a cell for it to continue on its journey to specialize as it replicates.”
Without the proper balance, the specialization process stalls. When that occurs, the cells reproduce but don’t ever fulfill their intended purpose. Instead, they pile up, compete and evolve, since the natural result of self-replication is evolution.
“What we need to do is inhibit some of the cancer cells’ ‘off’ enzymes and allow their specialization programs to turn ‘on,’” Dr. Saunthararajah says. “Basically, we want to renew the journey they started, and release their intended specialized destiny.”
Turning theory into science into medicine
Thanks to robust and diverse resources available at Cleveland Clinic, as well as support from national societies (the National Institutes of Health, the Leukemia and Lymphoma Society and the American Society of Clinical Oncology), Dr. Saunthararajah was able to team up with colleagues and develop a drug that can inhibit “off” enzymes in the body appropriately, without toxic side effects.
The drug, called THU-decitabine, already has been tested in a Phase I safety trial. This spring’s Phase II trials were performed to validate proof of concept.
The team also is investigating additional versions of the drug that can perform the same way.
“We need a few more iterations of the drug before we can really talk about this as a cure,” Dr. Saunthararajah says. “There’s still a one-in-a-million chance that a cancer can avoid one drug; the chance that it can avoid two drugs is one in a million squared, and it goes on like that. If we can develop two or three drugs like this, we will be on our way to a cure.”
Gifts that make a difference
Thanks to philanthropic support, Dr. Saunthararajah can run “an integrated drug-development lab that has as its guiding value the use of careful, rational and practical science to safely meet serious unmet human needs.”
The upcoming three clinical trials will study pancreatic cancer (the deadliest cancer), lung cancer (the most common cancer) and lymphomas (a cancer that affects young and old alike). Generous donations from private individuals, such as Mrs. Dane Miller, as well as members of the International Leadership Board, including Dr. Leszek and Mrs. Jolanta Czarnecki, helped make these trials a reality.
“Patients will be treated for at least a year if they are doing well on the drug,” Dr. Saunthararajah says, “and they can continue even beyond that, since we already know this treatment is not toxic. That’s why continuous funding is so important.”
Dr. Saunthararajah notes that medical breakthroughs are only impactful when they have been through all of the field’s well-established testing protocols.
“We got here by doing the rigorous science, day in and day out, and doing the clinical trials. We are going through the detailed process that is the only way to truly find out if the treatment is effective,” he explains. “If I had more funding, I would work on other awful cancers, like ovarian cancer and brain cancer. And I would transition this work to pediatric trials. Then I would work towards a cure by bringing in the second drug.”