How does Iclusig work (mechanism of action)?
Iclusig (ponatinib) is an oral small-molecule inhibitor designed to block several cancer-driving tyrosine kinases. It works by binding to the kinase domains of these targets and preventing them from signaling to the cell’s growth and survival pathways. This suppresses signaling from both normal and fusion/abnormal forms of the BCR-ABL pathway and related kinases. [1]
Which kinases does ponatinib inhibit?
Iclusig targets multiple kinases, including:
- BCR-ABL (including drug-resistant forms)
- The related oncogenic kinases KIT and others in the same signaling family [1]
Because BCR-ABL signaling drives the leukemia cells in chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), blocking it is central to Iclusig’s anticancer effect. [1]
Why does it help with drug-resistant BCR-ABL mutations?
In many cases of CML/Ph+ ALL, resistance to earlier BCR-ABL inhibitors comes from changes (mutations) in the BCR-ABL kinase domain that reduce how well those drugs bind or inhibit the kinase. Ponatinib is intended to inhibit BCR-ABL even when resistance arises from certain kinase-domain alterations, which is why it is used in patients whose disease has not responded to, or has progressed after, other therapies. [1]
What does “inhibiting tyrosine kinase signaling” do to cancer cells?
By shutting down kinase activity, Iclusig reduces downstream signaling that cancer cells rely on for:
- continued proliferation
- survival signals that help them evade cell death [1]
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Sources
[1] https://www.drugpatentwatch.com/p/iclusig-mechanism-of-action/