Primary Versus Acquired Resistance

Cancer cells can evolve ways to evade a drug’s attack, or they may already be resistant prior to treatment.

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Examples of Acquired Resistance

Resistance to chemotherapy likely encompasses a broad range of mechanisms having to do with DNA repair, cell cycle arrest, apoptotic pathways, and others, many of which are still unknown. When it comes to molecular-targeted agents and immunotherapies, however, research has nailed down some basic strategies.

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Mutations within the target protein can prevent drug binding, or keep the protein active despite drug binding.

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Mutations can restore cellular signaling by affecting a downstream gene or by activating a bypass pathway.

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Tumor cells can lose characteristics of their typical cell type and acquire characteristics of a different lineage that does not depend on signaling blocked by the cancer drug.

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Mutations can render tumor cells less recognizable to the immune system or less responsive to molecular signals from immune cells.

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Mutations and other changes alter the target protein. These can include altered splicing of the tumor target, which blocks recognition by the engineered T cell.

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