As strange as it sounds, some cancer cells can become “addicted” to treatment.
Researchers are finding that prolonged exposure to certain treatments can rewire cancer cells so deeply that they become dependent on the presence of the drug for survival.
When the drug is withdrawn, the cell can no longer sustain itself and dies.
“This puzzling phenomenon, which has been demonstrated in lab and animal models, and has been reported in patient case studies, suggests that certain tumours can sustain themselves through the very drugs designed to kill them” (Millar, 2018).
In 2017, researchers at the Netherlands Cancer Institute found that cells can become dependent on targeted therapies and that discontinuing the treatment causes them to die. The study focused on melanoma cells treated with BRAF inhibitors. Initially, these drugs blocked BRAF—a mutation that promotes tumor growth.
But over time, cancer cells adapted to the drug exposure by activating so-called “backup pathways” (such as ERK2 or other proteins) that restored the growth signal even with BRAF inhibited. This created a new survival mechanism that only functioned in the presence of the drug.
Instead of killing the cells, the drug held together a fragile survival program. When the drug was withdrawn, that system collapsed. The reactivated BRAF pathway became overactive, overwhelmed the cell’s control systems, caused toxic stress, and triggered cell death.
Another 2023 study published in Nature Ecology & Evolution came to the same conclusion. Withdrawing BRAF inhibitors from melanoma cells reactivated the BRAF pathway and overwhelmed the cell’s regulatory systems.
This surge led to uncontrolled signaling, oxidative stress, and activation of cell death pathways. Around 5 days of drug removal, tumors in animal models showed significant regression.
“When cells become resistant to particular drugs, they have to somehow compensate for the inhibitory effect of the drugs so they rewire their signalling pathways. If you acutely withdraw the drugs from these cancer cells, you disrupt the delicate balance between its rewiring and the potent action of the inhibitory drug. The cells will be unable to cope with the stress that emerges and they die – hence the word addicted” says Daniel Peeper, lead study author and professor at the Netherlands Cancer Institute.
It’s also important to note that cancer cell drug addiction usually happens when its survival becomes dependent on the suppression of a specific oncogenic signal.
For example, cell drug addiction has been recognized in:
- BRAF (melanoma)
- EGFR (lung cancer)
- ALK (lung cancer)
- BCR-ABL (leukemia)
- HER2 (breast cancer)
This kind of tight dependency is usually only created when you target a specific molecular feature (a protein, mutation, etc.) and is less likely than when you target the cell with general toxicity like chemotherapy.
So, what does this mean for clinical treatment?
Studies have shown that when cells start becoming addicted to the drug and resisting death, removing it is actually more effective than increasing the dose and trying to force a response.
“Drug holidays” or intermittent dosing can be used to exploit addicted cells. This can help kill cancer cells and improve outcomes by reducing the patient’s exposure to treatment-related toxicity.
Drug holidays can look like:
- 4 weeks on, 2 weeks off, a common intermittent schedule used in some targeted therapies (lenvatinib or sunitinib).
- Pause when tumor size stabilizes, then resume only when growth resumes (adaptive therapy).
- Fixed 5-day holiday after signs of drug resistance develop, especially in cells showing drug dependence.
- Dose skipping (treatment every other day instead of daily) to maintain effectiveness while minimizing toxicity.
The idea of “drug addiction” raises a deeper question: why would a cancer cell work so hard to adapt and survive, if it’s already so damaged?
There’s a common assumption that cancer cells are “immortal” or resist death, which is why they are so difficult to treat. However, cancer cells actually have a higher rate of death (also called apoptosis) compared to healthy cells. They just proliferate faster, which is why we see growth.
Cancer cells are already under enormous stress. The impulse to grow, divide, and adapt is not inherently malignant, it’s what the body does when it’s trying to heal damaged or stressed tissue.
The internal environment in cancer is inflamed, nutrient-deprived, or hypoxic, so the repair process goes haywire. The cell keeps trying to fix damage, but without the proper conditions or communication, it gets stuck in a dysfunctional loop. The cells aren’t rebelling, they are simply unable to repair.
So when we use treatments that target one single pathway, we layer on more stress. Unless the cell is already extremely weak, it adapts to handle even more extreme conditions. And in doing so, we may deepen the dysfunction rather than resolve it.
Because of this, we might need to use more than one therapy to effectively treat cancer, to rethink how we approach treatment, and to consider whether our goal should always be to destroy, or whether it should sometimes be to restore the conditions that allow the body to heal.
Your cells, including cancerous ones, are always trying to help you. They do everything in their power to sustain you, so they adapt to the stressors they face, and that includes drugs we use to kill them.
Sometimes the best medicine is to do nothing.
Obviously this is a complicated subject. But in certain cases, especially when treatment is failing or harming quality of life, pausing can be an effective therapeutic decision. A planned break is a chance to observe, to recalibrate, and to reduce the burden of treatment-related side effects.