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Why can cancer cells become resistant to targeted therapies?

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Precancerous growth in a human colon — cancer View through an endoscope of a polyp, a benign precancerous growth projecting from the inner lining of the colon.

Cancer cells can develop resistance to targeted therapies primarily through the emergence of new gene mutations. These mutations often alter the specific target molecule within the cancer cell, effectively disabling the drug's ability to bind to or interact with its intended target.123

Additionally, cancer cells may utilize alternative signaling pathways to bypass the blockade created by the therapy. For example, pathways such as the PI3K/AKT/mTOR network can become hyperactivated, promoting tumor survival and growth despite the presence of the drug. Because tumor cells are characterized by ongoing genetic instability and the accumulation of mutations, they possess a selective advantage that allows them to adapt and survive under the pressure of treatment.24

To mitigate the risk of resistance, oncologists often use targeted therapies in combination with one another or alongside conventional chemotherapy to attack the cancer through multiple mechanisms simultaneously.43