Research published in Cancer Cell in 2015 demonstrated that certain tricyclic antidepressants can disrupt glioblastoma cell survival by excessively activating autophagy, a cellular recycling process that normally helps cells survive stress. When autophagy is pushed beyond a tolerable threshold, however, cancer cells begin to digest their own essential components, leading to cell death. While antidepressants alone had shown limited therapeutic benefit in prior clinical trials, the researchers hypothesized that combining them with another class of drugs that also increases autophagy—blood thinners (anticoagulants)—could amplify this lethal effect in tumor cells (Shchors et al., 2015).
Using mouse models implanted with early-stage human glioblastoma, the researchers tested a combination therapy of an antidepressant given orally and a blood thinner administered by injection.
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The results showed a synergistic effect: mice receiving both drugs lived approximately twice as long as untreated mice, whereas either drug alone had no measurable impact on survival. Mechanistically, the two drugs interfered with different regulatory points in the autophagy pathway, causing uncontrolled, cell-lethal autophagy in tumor cells while sparing normal tissue. Although the treatment did not cure glioblastoma, it significantly delayed disease progression, highlighting a promising drug-repurposing strategy that warrants further investigation in combination with other anticancer therapies (Shchors, Massaras, & Hanahan, 2015).
