Julio Camarero, PhD

Treatment of lung carcinoma remains a great clinical challenge, and one candidate of interest is a novel type of compounds called cyclotides (MCo-52-2-based cyclotides). We plan to test cyclotides on several human lung carcinoma cell lines with different p53 phenotypes (null, mutated, and wild type), testing its efficacy on animal models of lung carcinoma; and to continue the development of this cyclotide selecting compounds based on cyclotide MCo-52-2 with improved activity. This will be accomplished by using the power of molecular evolution using cyclotide MCo-52-2 as template. Cyclotides with potent in vitro Hdm2/HdmX inhibitory properties will be further tested in vivo using several mouse models of lung carcinoma. We anticipate that this novel type of cyclotide-based inhibitor will have a broad spectrum of antitumor activity in human lung carcinoma cell lines both in vitro and in vivo. This could lead to the next generation of therapy of this type of cancer. 

Update:
This year we have tested our bioactive compound, MCo-52-2, in numerous human lung carcinoma cell lines, including small cell lung carcinomas (SCLC) and non-small cell lung carcinoma cell (NSCLC) lines. We have screened and tested novel MCo-52-2-based cyclotides and started to test cyclotide MCo-52-2 in several animal models of lung carcinoma. We are now using mouse models with several human lung carcinoma cell lines. Our preliminary results anticipate that this novel cyclotide-based inhibitor will have a broad spectrum of antitumor activity in human lung cancers with p53 genetic mutations, including SCLC and NSCLC, thus providing a novel basis for future therapy of human lung carcinoma.