Don’t forget to read Part 1 of our interview, where Todd discusses what acute lymphoblastic leukemia (ALL) is and why it is so important to raise awareness for ALL and other cancers. Today, in Part 2, we’ll discuss Mission Bio, the technology to help map ALL subtypes, and the struggles and rewards of working in oncology.
About Mission Bio
As described above, Todd works for Mission Bio; the research into the genetic underpinnings of ALL also utilized technology and tools developed by Mission Bio. So, what exactly is Mission Bio?
The Mission Bio “Company” page explains that:
We’re on a mission to enable researchers and clinicians to eradicate cancer.
Mission Bio was first started in 2014 with technology that came from the University of California – San Francisco to measure DNA targets in single cells. It is currently the only commercially available platform to identify multiple DNA mutations within a single cell. Because cancers generally arise from multiple DNA mutations and may acquire additional mutations that lead to treatment failure, many people feel that tools measuring multiple mutations in single cancer cells are the way forward in cancer diagnostics.
Mission Bio’s Tapestri device allows researchers and clinicians to measure DNA mutations across dozens of cancer-related genes and proteins marking the cancer cell surface in the same cell at the same time. “Our goal is not only to identify cancer cells that are likely to avoid standard treatment, but also give the oncologist information on what other treatments may be better for that particular patient. We’re bringing a new ability to see this co-occurrence in the same cell and working on showing how significant that is to improved patient outcomes, but we have a long way to go.
Developing Technology to Map Acute Lymphoblastic Leukemia (ALL) Genetic Mutations
Mission Bio developed the technology that St. Jude Children’s Research Hospital needed to begin creating a roadmap of genetic mutations associated with ALL. Todd explains that this study first used “bulk” (all the cells are destroyed en masse and the internal DNA is sequenced in one lump sum) sequencing. He shares:
You sequence the DNA from all of these cells together and you often can see several different mutations. However, is mutation A in the same cell as mutation B? That can matter. Sometimes they’re just benign mutations in healthy cells, but you need to test that to figure it out. The clinician is often guessing as to the order of events or the relative importance of the mutations. In an era where we have dozens of targeted cancer therapies available, we want to provide the highest resolution data to allow the oncologist to offer the best treatment option.
Within this study, the research team bulk-sequenced DNA from 2,754 pediatric patients with acute lymphoblastic leukemia. The research found 376 putative driver genes across various ALL subtypes, with a majority of ALL samples having at least one rare genetic alteration. Additionally, the research highlighted which patients failed treatments. Todd explains:
What the researchers then wanted to know was the series of events. What’s the first mutation that changes a normal cell into a cancer cell, and then what’s the next thing that makes that cell no longer responsive to treatment? Now the child’s disease comes back. So, the researchers used technology from Mission Bio for cases where they were able to identify the series of mutational events and how these potentially impacted the patient’s outcome. How could we treat these if we knew what to look for? What’s the sequence of events we need to watch for in order to potentially change treatment sooner?
These findings are incredibly important for the future of patient care. First, knowing the order of events in which mutations occur gives doctors something to look out for. By recognizing when something happens, the doctors can add the next level of treatment sooner – before a full-blown relapse.
Further, this kind of knowledge could also help oncologists to design more targeted and effective clinical trials. Through these trials, researchers can work to improve outcomes by pursuing more aggressive therapeutic options. Additionally, through clinical trials, researchers can evaluate therapies that may have fewer side effects for children. Currently, many cancer treatments come with toxicity or other side effects, ranging from fatigue and nausea to more severe symptoms. So, Todd says:
A good portion of the necessary research and studies should focus not just on how to cure or treat the cancer, but how to minimize additional toxicity. We want to make sure that these kids have the best chance of making it through school, getting a job, having a family – so let’s pivot sooner to something that works and avoid ineffective treatment. As pediatric oncologists, we have to give these children an entire lifetime. We can’t just focus on the next six months.
The Struggles (and Rewards) of Oncology
As a pediatric oncologist, Todd often worked with families who are going through difficult, time-consuming, and often overwhelming moments. While he wishes that he could provide additional treatment options or help, he notes that the lack of funding and research can make it difficult within this sphere. He shares:
Children’s cancer suffers significantly behind other conditions in terms of resources, research, and funding to bring new cures and research and getting pharma involved. Unfortunately, children, as a group, don’t have strong advocacy on their behalf. It’s not a lucrative business model. And that doesn’t make companies bad or evil, but this highlights a problem that many people within the rare disease realm experience: that there isn’t a critical mass to progress research. Some children with ALL or other cancers are still being treated with therapies developed in the 1970s.
Moving forward, Todd is hopeful that new technology can highlight how ALL, its subtypes, and other conditions are not just a single entity. Rather, these are unique diseases with unique causes that require unique treatments. Part of moving towards this goal is enhancing and celebrating the collaboration between different groups that are focused on a single goal. For instance, 20 institutions trying to study the same thing will dilute the statistical power of their results. However, when organizations (like the Children’s Oncology Group, a multi-institutional collaborative cancer trial network of >200 pediatric cancer treatment centers) work together, they can make tremendous strides in research. Many smaller grassroots groups, patient organizations, and philanthropic groups are also working together to advance research and education. They are optimistic that pharma will buy in after seeing the research.
Of course, Todd shares, this can be slow due to regulatory hurdles. But he hopes that by focusing on efficient and effective technology, the medical realm can begin bringing treatments to patients faster.
In the interim, Todd focuses on the science – and the rewarding nature of seeing his patients thrive. He shares:
A majority of children with cancer are cured, and the cure rate for ALL is actually quite high. It is incredible when I first see a very sick child and a scared family, and I’m able to get that child healthy and back to their favorite activities. I’ve been doing this for so long that I’ve even gotten graduation, marriage or birth announcements. Those are good days because I remember when they were struggling kids and how far they have come.