When you're told your metastatic cancer is incurable, most oncologists frame the conversation around managing inevitable resistance. But what if that entire framework is wrong?
Dr. Dawn Lemanne has spent her career asking a question most oncologists don't: "Why can't we reverse treatment resistance?" Her answer changed how I think about what's possible when standard treatments fail.
The Mathematics of Hope
Dr. Lemanne approaches cancer as an evolutionary process that can sometimes be steered. Not controlled,steered. The difference matters. "Cancer is development gone awry," she explains. Instead of accepting that tumors will eventually outsmart any drug, she studies their behavior patterns to stay one step ahead.
This is mathematics. Working with the Integrated Mathematical Oncology Department at Moffitt Cancer Center, Dr. Lemanne uses game theory,the same principles that govern chess strategy,to anticipate how tumors will respond to treatment combinations.
Here's how it works: when a tumor becomes resistant to one drug, it typically upregulates certain pathways to survive. But that adaptation often makes it vulnerable to a different treatment. Dr. Lemanne's team designs drug sequences so that as the tumor escapes one trap, it walks directly into another.
"We try to set up a series of drugs so that as the tumor becomes resistant to one, it becomes sensitive to the next treatment that's going to be applied," she told me. It's a double bind,tumor cells can't win both games simultaneously.
The Testosterone Paradox
A man whose prostate cancer had become resistant to androgen deprivation therapy, the standard approach of cutting off testosterone to starve hormone-dependent tumors. Instead of moving to harsh chemotherapy, Dr. Lemanne's team did something radical: they gave him the testosterone his cancer supposedly craved.
"That rescues some of the cells in the tumor that are sensitive to testosterone and allows them to repopulate the tumor," she explained. "They actually are a little bit stronger than their treatment-resistant brethren, because if you're a cancer cell, maintaining treatment resistance is a burden. Like carrying an umbrella. People who do not have to carry an umbrella in a foot race will win."
This isn't theoretical; they published the case. By cycling between testosterone and its absence, they kept this patient's cancer sensitive to treatment for far longer than standard protocols would allow. He got more good time, with a better quality of life.
The breast cancer applications are equally compelling. Dr. Lemanne works with patients using similar cycling approaches with hormone therapies, "toggling" treatments to manage side effects while prolonging sensitivity. "These patients have very long lives and very active non, non-symptomatic lives," she said.
Real-Time Intelligence
What makes this precision possible is measuring tumor behavior in real-time. Dr. Lemanne uses liquid biopsies, blood tests that detect circulating tumor DNA, to estimate tumor burden monthly. If that number goes up, the cancer is growing. If it drops, treatment is working. Simple.
"I thought, that's just not okay. We need to know in real time whether this treatment with its toxicities is actually doing anything beneficial," she said about the frustration of waiting months between scans.
For prostate cancer, she tracks PSA levels. For some breast cancers, she monitors tumor markers like CA 15,3 or CA 27,29. But here's the counterintuitive part: instead of driving these markers as low as possible, which oncology traditionally teaches, she keeps them cycling in a controlled range.
"It turns out that if you just make the PSA go down a little bit, like maybe 50% and kind of keep it between 25 and 75% you can make the sensitivity last a long time," Dr. Lemanne explained. Hammering a tumor marker down to zero is "the worst thing you could do if you want to create resistance."
The Future of Personalized Medicine
Dr. Lemanne's vision extends beyond just smarter drug scheduling. She has patients use continuous glucose monitors to track how meals affect blood sugar in real time, because high glucose can fuel tumor growth. She monitors sleep stages, exercise intensity, and even recent antibiotic exposure because all of these variables influence treatment effectiveness.
"Even very fit people who exercise a lot tend to overestimate how much they actually work out," she noted. Actual data reveals gaps between perception and reality that matter for cancer outcomes.
This reminds me of when Dr. Peter Kuhn discussed the importance of precision medicine; we need tools that work for the individual patient, not just statistical averages (you can hear that conversation at www.kcapodcast.com). Dr. Lemanne's approach takes that principle to its logical conclusion: every variable that might affect treatment response gets measured and optimized.
The N=1 Revolution
Perhaps most provocatively, Dr. Lemanne champions single-patient trials over large randomized controlled trials for metastatic cancer. Her reasoning is stark: "Breast cancer, lung cancer, colon cancer, pancreatic cancer have not been cured despite decades of large, randomized controlled trials. Completely failed. Not one cure."
The problem isn't the science, it's the approach. "We can have two people with the identical mutations within their cancer, and they may respond differently to the same treatment because there are so many other variables that come into play."
This connects to what Jessica Gravel learned during her treatment, that persistence and individual advocacy matter more than following standard protocols blindly (her story is at www.kcapodcast.com). Each person's cancer is unique, and their treatment should be too.
The Questions That Matter
Dr. Lemanne's work raises uncomfortable questions about how we've been thinking about metastatic cancer. If resistance isn't inevitable, why do we plan for it? If individual tumor behavior can be tracked in real time, why do we use population-based dosing schedules? If cycling treatments can prolong sensitivity, why do we give maximum doses continuously?
Most importantly: if mathematical oncology can make metastatic cancer genuinely treatable for decades rather than months, what are we waiting for?
Three questions to consider: How might your treatment change if your oncologist could see your tumor's response in real time? What aspects of your health could you measure and optimize to support your treatment? And if you could help design your own treatment protocol based on your tumor's unique behavior, what would you want to know?
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