Cisplatin combination chemotherapy is the cornerstone of treatment of many cancers. Initial platinum responsiveness is high but the majority of cancer patients will eventually relapse with cisplatin-resistant disease. Many mechanisms of cisplatin resistance have been proposed including changes in cellular uptake and efflux of the drug, increased detoxification of the drug, inhibition of apoptosis and increased DNA repair. Oxaliplatin is active in highly cisplatin-resistant cancer cells in the laboratory; however, there is little evidence for its activity in the clinical treatment of patients with cisplatin-resistant cancer. The drug Paclitaxel may be useful in the treatment of cisplatin-resistant cancer; the mechanism for this activity is unknown.
Cisplatin resistance-associated overexpressed protein, also known as CROP, is a human gene. This gene encodes a cisplatin resistance-associated overexpressed protein (CROP). The N-terminal half of the CROP contains cysteine/histidine motifs and leucine zipper-like repeats, and the C-terminal half is rich in arginine and glutamate residues (RE domain) and arginine and serine residues (RS domain). This protein localizes with a speckled pattern in the nucleus, and could be involved in the formation of splicesome via the RE and RS domains. Two alternatively spliced transcript variants encoding the same protein have been found for this gene.
Cleft lip and palate transmembrane protein 1-like protein (CLPTM1-like protein), also known as cisplatin resistance-related protein 9 (CRR9p), is a protein that in humans is encoded by the CLPTM1 gene. CRR9p is associated with cisplatin-induced apoptosis.
Cleft lip with or without cleft palate is a common birth defect that is genetically complex. The nonsyndromic forms have been studied genetically using linkage and candidate-gene association studies with only partial success in defining the loci responsible for orofacial clefting. CLPTM1 encodes a transmembrane protein and has strong homology to two Caenorhabditis elegans genes, suggesting that CLPTM1 may belong to a new gene family. This family also contains the Homo sapiens cisplatin resistance related protein CRR9p which is associated with CDDP-induced apoptosis.
Thiostrepton was reported (in 2008) to exhibit activity against breast cancer cells through targeting the transcription factor forkhead box M1 (FOXM1) also in 2011. It has also been shown to circumvent acquired cisplatin resistance in breast cancer cells under in invitro conditions.
See also: http://en.wikipedia.org/wiki/Cisplatin
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