PharmaMar, a biopharmaceutical company owned by Grupo Zeltia (ZEL.MC), presented six new trials with marine-based anti-tumor drugs Yondelis(R), Zalypsis(R) and Irvalec(R) at the American Association for Cancer Research's (AACR) 101st Annual Meeting, held in Washington, D.C. from April 17-21.
The AACR meeting is the leading convention on cancer research, bringing together more than 17,000 attendees each year and covering breakthroughs in oncology and basic, clinical and epidemiological research.
Two trials provided new data on Yondelis(R) (trabectedin), a marine-based anti-tumor drug currently produced by chemical synthesis. Yondelis(R) (trabectedin) has European Commission approval for advanced and metastatic soft tissue sarcoma (STS) and for recurrent platinum-sensitive ovarian cancer in combination with Doxil/Caelyx.
Various in vitro trials have shown that trabectedin's activity depends at least partly on the nucleotide excision repair (NER) mechanism. A new trial is evaluating if the status of ERCC5 (XPG), an endonuclease-3 that plays a key role in the excision of damaged DNA, is linked to trabectedin's clinical activity in patients with advanced soft tissue sarcoma.
New data suggests that overexpression of the wild-type ERCC5 gene may be a predictor of beneficial effects of trabectedin in patients with advanced STS.
A second trial is analyzing in vitro and in vivo activity of trabectedin in a group of 67 human tumors with a view to identify a common genetic profile and pinpoint Yondelis(R)-sensitive tumors. The results of this analysis demonstrate the viability of combining experimental trials with virtual prediction to identify other tumors that are potential candidates for new preclinical and clinical trials with the compound. Phase II clinical trials are currently under way with Yondelis(R) in breast, lung and prostate cancers and pediatric tumors.
Three other trials presented at the AACR meeting provided new data on Irvalec(R), a novel marine-based synthetic depsipeptide currently in Phase II trials for lung cancer.
The first trial is evaluating the modulation of initial cytotoxic effects of Irvalec(R) using zinc and DIDS in lung cancer cells. The results suggest that plasma membrane damage caused by Irvalec(R) generates a rapid onset of hydroelectrolyte imbalance, causing severe alterations that lead to cell death by necrosis.
A second trial sheds light on the molecular mechanism associated with sensitivity and resistance to Irvalec(R). Conclusions show that primary and acquired resistance to Irvalec(R) may be associated with the expression of ErbB receptors and epithelial mesenchymaltransition markers.
A third trial shows that overexpression of ErbB2 and ErbB3 receptors does not affect sensitivity to Irvalec(R), although the receptors do suffer some changes as a result of alterations in the cell membrane produced by the compound.
Another trial suggests that PDGFRA could be a useful predictive biomarker of response to Zalypsis(R), a novel chemical entity related to the marine natural compounds jorumycin and the renieramycin family, obtained from mollusks and sponges. Zalypsis(R) is currently in Phase II trials for endometrial and cervical cancer.
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