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Hitting cancer where it hurts: Mixed opioid somatostatin ligands as tomorrow's anti-cancer targe
Added: 02/25/2002

Target identification specialists at LeadDiscovery, the drug discovery, development and transfer consultants, have recently focused on a series of compounds that fits just this profile.

Human breast cancers have long been known to express somatostatin SSTR2 receptors and indeed this has been exploited by companies looking for improved ways of imaging breast tumors, with radiolabeled molecules that specifically bind to and "light up" these receptors. For a long time however it has also been suggested that activation of these receptors reduces the proliferation of breast cancer cells suggesting that SSTR2 agonists may seek out and destroy these cells. Like SSTR2 receptors, k opioid receptors are also expressed by certain breast cancer cells and similarly, activation of these receptors also reduces cell proliferation.

In addition, to being able to reduce cancer growth, the analgesic activity of SSTR2 and k opioid receptor ligands has also been proven. A convincing body of evidence therefore suggests that mixed or pure SSTR2/k opioid receptor agonists may offer hope for breast cancer patients, reducing tumor progression and associated pain.
According to senior analyst at LeadDiscovery, Dr Jon Goldhill, "it is astonishing that the potential of such compounds has not yet been exploited by the pharmaceutical industry. Nearly 25% of all drugs in development are for the treatment of cancer and over 10% of these are specifically for breast cancer - yet none of these target somatostatin or kappa opioid receptors. Perhaps even more astounding is the lack of molecules that can directly treat both tumor progression and related pain".

As is often the case however, the success of nature has preceded that of the pharmaceutical industry. Ironically the very molecules that could treat breast cancer are derived from the breast.


Caseins comprise about 79% of total bovine milk proteins and in their recent DiscoveryDossier, LeadDiscovery places the spotlight on the anti-cancer activity of casein derivatives and their homologues. These derivatives termed casomorphins and a similar molecule termed receptorphin, each of which contain a similar short peptide sequence, bind to k opioid and in some cases somatostatin receptors producing extremely potent anti-cancer activity.

While exciting, further studies are required to exploit these findings. First and foremost, although these molecules are expected to have analgesic properties, this must be demonstrated, preferably in models of cancer pain. Secondly, even though anti-cancer activity has been demonstrated in test tubes, studies must be carried out in animal models more closely mimicking tumor progression.

Continues Dr Goldhill, "such studies would be simple to perform - we would even be prepared to arrange for them to be performed. We believe that once data has been obtained showing that these molecules prevent both cancer progression and pain, the race will be on to develop casomorphin-like molecules into therapeutically useful drugs. Since these molecules are peptidic, further chemistry will likely be necessary to produce stable mimics or alternatively non-peptide molecules will have to be identified through high-throughput screening or molecular modeling approaches. However, such studies represent day to day practices of most pharmaceutical and biotech companies".

In short, once again nature has given us clues on how to treat one of the most common causes of death - these clues have been before our eyes since the evolution of man - it is now our turn to turn these clues into cures.

For further information access " Novel targets for breast cancer: Halting tumor progression and pain" at http://www.leaddiscovery.co.uk/reports/breast cancer.html

LeadDiscovery is a UK based pharmaceutical consultancy company supported by a web platform (www.leaddiscovery.co.uk) offering three key services. TherapeuticAdvances is a bulletin of cutting edge research with commercial potential circulated to over 4,500 industrial personnel. DiscoveryDossiers represent in depth analyses of drug discovery options selected by LeadDiscovery specialists or produced for institutions wishing to stimulate strategic partnerships. PharmaceuticalSolutions is a client-lead service through which LeadDiscovery is able to offer advice and project management relating to pre-clinical target selection and drug development.



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