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Vorinostat + pemetrexed + cisplatin is a combination regimen of three chemotherapeutic agents used in clinical trials for advanced solid tumors, including non-small cell lung cancer and malignant pleural mesothelioma. Vorinostat is a histone deacetylase (HDAC) inhibitor that induces cell cycle arrest and apoptosis by inhibiting HDAC1, HDAC2, HDAC3, and HDAC6. Pemetrexed is an antifolate antineoplastic agent that disrupts folate-dependent metabolic processes essential for cell replication by inhibiting several enzymes involved in purine and pyrimidine synthesis. Cisplatin is a platinum-based chemotherapy drug that forms DNA crosslinks leading to apoptosis. The combination aims to enhance antitumor activity through complementary mechanisms: epigenetic modulation (vorinostat), inhibition of nucleotide synthesis (pemetrexed), and direct DNA damage (cisplatin). This regimen has been evaluated in phase I/II studies for safety and efficacy in patients with advanced or refractory solid tumors[2][3][8].
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