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It was recently shown that pemetrexed may play a role in cisplatin resistance in lung cancer by increasing the expression of Orai3 calcium channels as well as the expression of certain ABC transporters like MDR1 and MRP-5 responsible for cisplatin efflux and therefore a reduction of the effect of cisplatin [16] As current therapies are based on the co-administration of pemetrexed and cisplatin, there may be interactions between pemetrexed and cisplatin, including a reduction in the therapeutic effects of cisplatin caused by pemetrexed

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Despite promising in vitro and in vivo efficacy, validation remains limited to two cell lines and animal models

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In cancer cells, the demand for Gln increases and its metabolism is often rewired to meet the unique metabolic requirements associated with tumorigenesis and rapid proliferation