Avastin - Abstract 117: Novel therapeutic approaches: molecular targeted therapy
Citation: European Journal of Cancer Supplements Volume 3, No. 2, October 2005, Page 31
S.B. Kaye
Institute of Cancer Research, Medicine, Sutton, United Kingdom
Progress in the management of ovarian cancer has been slow over the past 10 years despite the considerable chemosensitivity of the disease.
In most cases, drug resistance supervenes after repeated courses of treatment, and novel molecular targeted drugs are therefore being explored using a range of approaches.
One of the most promising targets is VEGF which is an angiogenic growth factor of particular biological importance in ovarian cancer. As a single agent, the anti-VEGF monoclonal antibody, Avastin, has demonstrated antitumour efficacy in advanced disease.
Large-scale randomized trials, combining paclitaxel/carboplatin with Avastin, both during and in consolidation treatment following chemotherapy, are planned for first-line studies.
Increasing attention is being paid to the treatment of relapsed disease, and planned trials in this context include combinations of carboplatin with the demethylating agent, decitabine, which has the ability to reverse resistance in experimental models.
Other molecular targets include the ErbB family of receptors, and clinical trials will involve both the small molecule inhibitors and the monoclonal antibody, Omnitarg.
Interestingly, the one response to the EGFR inhibitor Gefitinib in a Phase II trial in ovarian cancer was linked to a mutation in the catalytic domain of the receptor, in a manner similar to that found in non-small cell lung cancer
[1].
Anti-angiogenic agents are also receiving considerable attention in the context of relapsed disease; in addition to Avastin a range of small molecule kinase inhibitors show promise in this respect, and will shortly enter randomized trials.
Other pathway-specific molecules may well find a role in ovarian cancer, particularly those such as HSP90 inhibitors which affect the P13 kinase-AKT pathways, which may play a central role in drug resistance.
In this context, combinations with taxanes may be particularly appropriate.
Ultimately, real progress may be expected by a better understanding of the key signalling aberrations causing drug resistance; novel molecular targeted agents – probably in conjunction with conventional chemotherapy – may then be utilized in patients most likely to benefit [2].
References:
1. Schilder R, Sill M, Chen X et al. Phase II study of Gefitinib in patients with relapsed or persistent ovarian or primary peritoneal cancer and evaluation of EGFR mutations and immunohistochemical expression; a GOG study. Clin. Cancer Res 2005; 11, 5539–48.
2. Agarwal R, Kaye S. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev: Cancer 2003; 7, 502–16.
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