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Pemetrexed + zibotentan is an investigational combination therapy evaluated for the treatment of advanced non-squamous non-small cell lung cancer (NSCLC) in patients who have failed prior platinum-based chemotherapy. Pemetrexed is a small molecule antifolate antineoplastic agent that inhibits multiple folate-dependent enzymes involved in nucleotide synthesis, thereby blocking DNA and RNA synthesis and inhibiting tumor cell proliferation. Zibotentan (also known as ZD4054) is a highly selective endothelin A receptor antagonist; it blocks the action of endothelin-1 on the endothelin A receptor, which may reduce tumor growth and progression by inhibiting pathways involved in cell proliferation and survival. The combination was studied to assess whether adding zibotentan to standard pemetrexed therapy could improve outcomes in NSCLC patients[1][2][3].
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