A hallmark of cancer cells is their ability to evade apoptosis,1
a highly regulated form of cell death. Although investigators have become heavily invested in identifying ways to reactivate apoptosis in tumors, designing drugs that rejuvenate this process while avoiding indiscriminate killing of normal and cancerous cells has proved challenging.
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Now pharmaceutical companies are developing novel platforms to yield a new generation of drugs,7
with clinical trials ongoing across a range of solid and hematological malignancies (Table
). Meanwhile, results from a first-in-human study into ABBV-621, a TRAIL receptor agonist, highlight the potential of focusing on TRAIL.8-10
As development of TRAIL-targeting drugs moves forward, many questions about the signaling network and its function in cancer apoptosis continue to be unraveled. These include the nature of intrinsic and acquired resistance to TRAIL-targeted drugs.
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