Competitive update: PLK1 inhibitors for cancer
Joan Baez
The same approach could very well apply to Pharma and Biotechnology companies managing their pipelines and drug portfolios. Everything is about what's happening right now and what can be done to move the development along to market, preferably as fast as possible.
Increasingly, the oncology market is becoming more and more complex with both chemotherapy and targeted therapies and different combinations, sequencing and mechanism of actions all playing their part. As we learn more about the science and biology of each cancer type, so there is a proliferation of different inhibitors designed to target specific pathways. A part of this ongoing series, today we look at PLK1 inhibitors.
According to an article in Nature, Polo-like kinase 1 (PLK1) is essential during mitosis and in the maintenance of genomic instability, as well as being overexpressed in some tumours (NSCLC, oropharyngeal, oesophogeal, melanoma, NHL), which may offer some prognostic potential. It is yet unclear whether it is critical to tumourigenesis and hence useful as a therapeutic target, but cell cycle inhibitors are clearly worth a punt.
There are a number of PLK1 inhibitors in development. These include Scytonemin, a natural marine product that was originally being developed by SKB and now appears to be under the auspices of Merck KgA and EMD, ON01910 (Onconova Therapeutics), Wortmannin and BI 2536 (Boehringer Ingelheim).
The most advanced programs at present are BI2536 and ON 01910, which are both in phase I development. ON 01910 is being tested
in over 90 different human cancers, both as a single agent and with
other existing cancer drugs. Johns Hopkins Medicine and Mt. Sinai
Medical Center are conducting the first clinical trials of
ON01910 in patients with advanced and metastatic cancers.
It is too soon to tell how effective these agents might be, but the class has a solid scientific rationale and some interesting data may therefore be available at the annual AACR meeting in 2009.
{Update – new data has been released on BI 2536 at the EORTC-NCI-AACR meeting at ECCO in Geneva this week – you can find out more here.}