CancerCancer - The Disease
Cancer is a disease of uncontrolled cell proliferation which, left untreated, may ultimately kill the patient. Over time, cancer tends to spread or metastasise to other tissues and organs of the body. Cancers are divided into: Typically, a solid tumour cancer that is detected early in its progression and has not spread to other organs and tissues will have the best prognosis. In this case, surgical removal of the tumour may be curative. In contrast, cancer that is detected at a later stage may be more difficult, or impossible, to cure. Even when detected early, cancer cannot always be cured through surgery. This may be because the entire tumour cannot be surgically removed or because the cancer may have already spread to other parts of the body through metastasis, the spread of undetectable cancer cells. A solid cell tumour cancer, even if discovered at an early stage, may have already entered the blood or lymphatic system and established new tumours, consisting of cancerous cells from the original or primary tumour, at other locations in the body. Cells and tumours formed at these new sites are extremely difficult to treat and the prognosis of a patient with metastasised cancer is poor. For haematological malignancies, which are already in the blood stream or lymphatic tissue, surgery is not an option. In such circumstances these are treated primarily with chemotherapy and in addition sometimes with radiotherapy.Cancer Prevalence
According to the WHO (World Health Organization), more than 10 million people are diagnosed with cancer every year and this incidence is expected to increase by 50% over the next 20 years. Cancer is the second biggest cause of mortality and is responsible for around 6 million deaths every year - or 12% of deaths world-wide. Despite improvements in treatment and diagnosis in the last 50 years, there is still a great need for new therapeutics which are: Most current chemotherapeutics have unpleasant side-effects including nausea, diarrhoea, myelosuppression, hair-loss and cardiotoxicity.
Cancer - The Biology
Recent advances in understanding the human genome have helped scientists to understand the development of cancer. Cancer is caused by a series of errors in the genes, the most important of which are as follows:
1. Accelerator genes or oncogenes, which cause cells to divide, are controlled in healthy cells but uncontrolled in cancer cells;
2. Brake systems or suppressor genes, which function to suppress cell proliferation, fail;
3. Suicide or apoptopic genes, which cause malfunctioning cells to commit suicide, are silenced;
4. A control system that prevents a healthy cell from dividing limitlessly is bypassed; and
5. Through angiogenesis, the cancer cell recruits blood supply from healthy cells, destroys adjacent tissues and moves or spreads throughout the body. This produces a new metastasised tumour in a different part of the body from the original or primary tumour.

Redundancy of Treatment
The genes used by a cancer cell are part of a complete network of inter-locking mechanisms and the cancer cell may use a number of different pathways to develop. This redundancy causes immense pharmaceutical problems, as most or all pathways have to be blocked to achieve effective treatment. Many of the favoured targets of modern anti-cancer drug development, which include apoptosis, metastasis, and angiogenesis, suffer from problems of redundancy in that they may fail to block other potential pathways of cancer. New methods of cancer drug development prioritise targets that are essential to cancer development and therefore non-redundant. The Company believes that its principal targets may be non-redundant. For example, topoisomerase enzymes are critical to cell division and histone deacetylases appear to be responsible for governing the central processes by which genes are controlled.

Resistance to Treatment
Generally, by the time a cancer tumour is diagnosed it will be at least one centimetre in diameter and contain more than a billion cancer cells. The unstable chromosomal structure of cancer cells gives rise to mutations, generating cellular diversity and increasing the likelihood that one or more cells may be resistant to one or more cancer drugs. Resistance is a significant problem in oncology and may lead to relapse and the recurrence of cancer, either during treatment or at a later stage. The widespread frequency of resistance has historically meant, with only one rare exception, that no single drug has been able to cure a cancer disease. As a result, cancer treatments generally involve the administration of a combination of different chemotherapeutics, each having different mechanisms of action and toxicity features. TopoTarget actively seeks the most promising combinations to administer its drugs to patients.
Administration of drugs with different toxicities allows higher combined dosages than would otherwise be possible. The objective in cancer treatment is to develop drugs that do not generate resistance, and a non-cross resistant drug that could be administered in effective dosages that would kill cancer cells but not healthy cells would ultimately be the most effective. In reality, however, resistance is a general difficulty within oncology and expectations are that patients will continue to be prescribed various combinations of available drugs or treatments that may be effective. Many oncologists believe that cancer may ultimately become a chronic, rather than an acute disease, requiring ongoing treatment.