Speed Is the Story: How Sequencing the Human Genome Transformed Cancer Care

When Joyce Ohm, PhD, started her career in cancer research, the human genome hadn't been sequenced yet. Today, she runs a department built around the idea that reading a tumor's genetic code as fast as possible is the single biggest lever oncology has for changing how patients are treated.

In an interview with Targeted Oncology, Ohm, chair of the Department of Cancer Genetics and Genomics, John & Santa Palisano Endowed Chair of Cancer Genetics at Roswell, Park Comprehensive Cancer Center, discussed how the initial completion of the Human Genome Project in 2003 has advanced cancer research and treatment.

What Decoding the Genome Actually Changed

To Ohm, sequencing of the human genome has shaped cancer therapeutics primarily through velocity. "What it's really done is accelerate dramatically everything that we do," she said. "For decades, we had sequences of individual genes, for instance, but the ability to look at the entire genome has allowed us to discover new targeted therapies at an accelerated rate."

That acceleration shows up across several distinct problems in cancer treatment, she explained. "It's allowed us to find different gene mutations that may be driving treatment response and resistance. It's allowed us to identify new vulnerabilities for different targeted therapies. All of those things now we can do rapidly in a way that we really couldn't before."

For Ohm, that speed isn't a side benefit; it's the foundation the entire field of personalized medicine rests on. "The idea that we've moved on almost completely into this world of personalized medicine and targeted therapies is all completely dependent on our ability to see cancer mutations and see them quickly enough to actually allow us to change therapeutic approaches based on that," she said.

How Sequencing Powers Cell and Gene Therapy

Ohm drew a direct line between genomic sequencing and the design of modern cell and gene therapies, including in her own field of sarcoma research. "In the case of cell therapy, they're targeted to a tumor antigen on the cell surface, and so the ability to see those abnormal gene changes allows us to develop a targeted therapy specifically attacking them,” she said.

Without that visibility into a tumor's genetic makeup, the entire approach falls apart. "If we can't sequence those tumors and identify the changes that are in those tumors, we don't have the ability to develop the targeted therapies to them," Ohm said. "So, it becomes really important for us to be able to see what's normal and abnormal and then develop therapies specifically targeted to those." She noted that the same logic extends to epigenetically targeted treatments, and that the mutations driving any given tumor can have very different origins. "Sometimes those are unique mutations that are patient dependent, or sometimes they're underlying mutations that have been passed down from generation to generation."

The Ethical Weight of Moving Fast

Rapid progress, Ohm said, has come with real ethical friction, and the sequencing of the human genome is, in her view, a particularly clear example of that tension. "I think with any rapidly advancing technology, we always have the ethical challenges that come along with that," she said. "I think the sequencing of the human genome has been particularly fraught with that. I think science advances so quickly that sometimes we have to wrestle with the human side of that."

"It's an area that I think brought fear and confusion in many ways, but fortunately, we've been able to tackle a lot of that," Ohm added, pointing to the parallel growth of dedicated ethics infrastructure. "There are amazing scientific ethics panels that have been built up along with the sequencing of the human genome. So, you've seen that whole field grow up alongside this."

Even with that infrastructure in place, Ohm said some of the hardest questions remain genuinely unresolved. "I think there's still outstanding questions about what it actually means to sequence a human's genome. Who owns that data? What do we do with that data? And at what point is it helping vs hurting?"

"I think…it's overall been a huge net positive, because it's allowed us to advance the field rapidly. But we do have to make sure that we're doing the best for our patients all along the way," she said. "Part of that is also being measured in our approaches."

One example she returns to is the everyday clinical reality of finding a mutation whose meaning isn't yet known. "We can identify mutations in a patient's tumor right now, but we don't always know what they mean. We know it's abnormal, we just don't actually know the significance of that mutation, for instance," she said. That uncertainty creates a genuine dilemma for physicians. "You have to wrestle with that. Do you report a mutation back to a patient if you don't know what it means? That can cause fear and confusion."

The Next Frontier: Truly Personalized Medicine

Regarding the next major breakthrough in cancer therapeutics, Ohm doesn't point to a new technology so much as a more complete realization of one already underway. "I think the next big thing is absolutely moving into truly personalized medicine," she said. "This idea that every patient is an individual, their tumor is an individual tumor, and so we have to find absolutely the best treatment for any individual patient and their disease."

Progress toward that goal is visible but incomplete, in her view. "We're getting there. You start to see, with the identification of these actionable mutations and understanding what those mean, physicians being able to make good choices for their patients and choose one treatment vs the other," she said. "But we still have a long way to go there in terms of truly understanding the molecular drivers of any patient's tumor and being able to really develop a truly targeted therapy that hits that tumor."