ranpirnase + pemetrexed + carboplatin

This is a combination regimen consisting of **ranpirnase**, **pemetrexed**, and **carboplatin**, investigated as an anticancer therapy. - **Ranpirnase** is a ribonuclease enzyme (RNase) originally isolated from the Northern Leopard Frog that selectively degrades transfer RNA (tRNA) within tumor cells, leading to inhibition of protein synthesis, cell-cycle arrest, and induction of apoptosis, often by caspase-dependent pathways. It has demonstrated selective activity toward malignant cells, with a favorable toxicity profile compared to conventional cytotoxics[2][4][8]. - **Pemetrexed** is a folate antimetabolite that inhibits multiple enzymes involved in folate-dependent metabolic processes essential for cell replication, particularly thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase, thereby interfering with DNA and RNA synthesis in rapidly dividing cancer cells[3][1][5]. - **Carboplatin** is a platinum-based chemotherapy agent that induces DNA crosslinking, leading to DNA damage and apoptosis in rapidly dividing cells[3][1][5]. The rationale for this combination is to exploit synergistic cytotoxic effects of RNA and DNA synthesis inhibition (by ranpirnase and pemetrexed) with DNA crosslinking and damage (by carboplatin). The combination aims to improve anti-tumor efficacy in solid malignancies, particularly non-small cell lung cancer (NSCLC) and malignant mesothelioma, though clinical development of ranpirnase has focused more on combinations with other agents such as doxorubicin[2][4]. Pemetrexed plus carboplatin, without ranpirnase, is established in NSCLC and mesothelioma, while the triplet with ranpirnase has limited published clinical experience.