The biological complexity of cancer is individual to each patient, and it presents many roadblocks on the path toward optimal treatments. However, developments in DNA technologies and advanced imaging tools have greatly informed clinicians and researchers on ways to develop methods for precision care.
Morgridge biomedical imaging investigator Dr. Melissa Skala and University of Wisconsin–Madison medical oncologist Dr. Mark Burkard, joined Gabriella Gerhardt on December 6 for a webinar in the Fearless Science Speaker Series about the future of cancer care. The following highlights are some of the key takeaways. A recording of the webinar can be viewed in full above.
Currently, cancer treatment decisions are made based on several different questions: which drugs are most effective, how toxic is each drug, will there be side effects, etc. This is an iterative process, which can take weeks or months to determine if a patient is responding well. If not, the treatment plan is changed and the process starts over.
“I think of this as more of a compass where we’re thinking about what direction we can go, what options are available to us. It’s a general guideline,” Skala says. “Of course, we’d like to see something more precise, more of a GPS, what exactly to do to optimize this treatment plan for each patient so that they can achieve good health and long survival.”
Scientists are using organoids, small clusters of cells that function like a “tumor in a dish” to better replicate the disease environment. However, many times the cells are destroyed during drug testing or experimentation.
The Skala Lab is using new technologies to monitor treatment responses while keeping the organoids alive so they can watch them adapt over time. They do this by measuring changes in metabolism, the way energy is produced and consumed in a cell.
“We know that cancers derived from cells that are dividing uncontrollably, so logically, it kind of makes sense to think about cell metabolism as a method of measuring a cancers response to treatment and its potential to grow in the future,” says Skala.
Skala and her team use a method called optical metabolic imaging (OMI) to measure these cell responses by identified the natural fluorescence emitted by the cells. By imaging specific organoids grown from patient biopsy samples, they can hopefully collect more data to make patient-specific decisions more quickly.
Traditional therapies like radiation or chemotherapy target all cells, both healthy cells and cancer cells, resulting in undesired side effects. But cancer immunotherapies can be more selective for the specific cancer cells.
Chimeric antigen receptor therapy, or CAR T-cell therapy, uses a patient’s own immune cells by reprogramming the T cells to fight cancer. Some CAR T-cells will be highly effective and produce the cancer killing molecules needed, but some will be less potent. The Skala Lab is using their OMI technology to ask the question, “how can we identify them so that we can promote those types of CAR T-cells in the patient product so they have a better response?”
Currently, the lab is working on ways to make their imaging system smaller and more cost effective, with hopes to get closer to developing one that could be easily used in a clinical setting.
Skala credits much of their work to the wonderful collaborations with people at UW–Madison like Dr. Burkard and Dr. Dustin Deming, who developed the Precision Medicine Molecular Tumor Board at the UW Carbone Cancer Center. Through their services, a patient can be referred and a genomic report is generated from their own tumor biopsy to inform decisions for care.
“I like to think of them as a brain trust, all these smart people around a table thinking about what could be best for a patient based on their genomic report,” Skala says.
Burkard says that all of this is possible due to the completion of the Human Genome project back in 2003, a project that took over a decade and $3 billion to sequence one single human reference genome. While the DNA sequencing technology used at that time is now outdated, new sequencing methods can do that whole project in less than a day at a reasonable cost.
“For 2 billion base pairs of your DNA, we could sequence that for the cost of a new exhaust system on your car,” Burkard says. “And so we could do that not only in people, but also in their tumors.”
This is an important distinction, Burkard says, because cancer growth is fueled by genetic changes.
He adds: “cancers are hard to treat, because they’re inherently part of a person. Something additionally happened that turned a healthy cell into cancer. If you want to find what’s driving an individual person’s cancer, therefore, you have to test the tumor itself.”
Finding rare genetic mutations within a tumor can be extremely helpful for making treatment decisions. The Precision Medicine Molecular Tumor Board uses the data to identify a standard treatment or a clinical trial or an off label treatment, which means a treatment approved for another cancer, that makes sense based on the genetic change.
“It shows the power of finding rare mutations, that it’s worth looking for these needles in a haystack,” Burkard says. “Because if you find something that’s uncommon, you may be able to find a real unique, but effective way to help a patient.”
The Burkard Lab is also interested in using DNA sequencing technologies to answer a common question he often gets from patients: “now that the treatments are done, is my cancer gone?”
Cancer can result in distant recurrence, when metastatic disease develops in another part of the body many years later. While clinicians can do regular scans for tumors, it still won’t pick up individual smaller lumps of cells that may be growing.
So Burkard and his team are working on a new technology called minimal residual disease detection, which detects DNA that’s circulating in the bloodstream.
“I envision in the in the future, we’re going to have, I hope, improved methods for early detection,” Burkard says. “I imagine we’re going to take every cancer patient who walks through the clinic and offer them gene testing, and maybe test the tumors as well to allow us to select the best treatment for each patient.”
Skala and Burkard both agree that the most hopeful aspect to their work is the people — from stories of patients and their fight against disease, and thoughtful collaborators working hard toward better solutions.
“I’m inspired by people trying new things that you wouldn’t have thought would be blended like engineering and oncology,” says Skala. “That, to me is an important intersection where we could be creative and think of innovative solutions.”
Burkard adds: “I’m inspired by my patients who are living in unexpected ways. And it’s humbling every day to deal with this disease and to work with patients and to learn more.”