"Smart Therapies" - A Hope for the Future

There is emerging evidence to indicate that in the next 10-15 years we will see a dramatic change in the types of chemotherapies offered to cancer patients. These "smart therapies" will deliver pain-free cures for cancer in the future.

Treatment of cancer is undergoing a continuing evolution that is improving the prospects of cancer sufferers. In this article, Associate Professor Nicholas Saunders outlines some of the “smart therapies” that are showing particularly promise.

The diagnosis of cancer is a serious and traumatic event that will impact everyone directly or indirectly. In 2004, almost 100,000 people were diagnosed with cancer and 40,000 cancer deaths were recorded in Australia. Whilst most cancers are life-threatening, patients are often more concerned about the traumatic nature of the treatment rather than the disease itself. Amongst the most serious concerns for patients is chemotherapy and its associated side effects. To a certain extent this fear is justified. For example, many of the current chemotherapeutic agents are relatively non-specific in nature and for this reason they tend to be associated with serious side effects such as diarrhoea, skin and mucosal reactions, hair loss and immune suppression.
 
Despite these side effects, there is optimism for the future of cancer treatment. There is emerging evidence to indicate that in the next 10-15 years we will see a dramatic change in the types of chemotherapies offered to cancer patients. Most importantly, the types of chemotherapeutics that are being developed are selective and relatively non-toxic to normal tissues. The development of these new “smart therapies” stems from the enormous advances that have been made in biomedical sciences in the last 10 years.

For example, the sequencing of the human genome gave birth to a new field of mathematical biology called bioinformatics. Bioinformatics has provided scientists with a tool to sift through the human genome and piece together all the genes in the body and the specific biological pathways they are involved in. Similarly, advances in biological sciences have led to the development of techniques which allow us to add or remove an individual gene or genes in living cells and animal models, allowing us to identify genes critical to the survival and development of cancer cells. While this may all seem a little academic, the application of these advances will improve outcomes for patients. If we can identify genes and functions that are specific to the survival of cancer cells, for instance, these can be specifically targeted when developing new therapies.

The application of new scientific knowledge to the treatment of cancers is commonly referred to as “translational research”, so named because it translates the advances made in biological sciences into improved treatments for patients. Ultimately, the application of this knowledge will accelerate the development of “smart therapies” that kill cancer cells and leave healthy cells untouched. Whilst this may sound too good to be true it should be remembered that diseases such as hypertension, bacterial infections and diabetes are all treated by selective therapies that target only the disease or symptoms and therefore do not cause massive side effects. Thus, our goal as translational scientists is to deliver anticancer therapies that are as selective and tolerated as well as the therapies for other major human diseases.

New “smart therapies” for cancer treatment are already in use for some cancers and newer agents are being trialled for many other types of cancer. For example, the overall long term survival rate for breast cancer is approaching 90 per cent. One of the major advances contributing to this success rate was the development of so-called anti-oestrogens such as tamoxifen, or the newer aromatase inhibitors that selectively target oestrogen action in breast cancer cells. These therapies work because we know that the majority of breast cancers are oestrogen-dependent and for this reason inhibiting oestrogen action removes an essential growth factor for these cancers. More recently, it was discovered that a small fraction of breast cancers overexpressed a receptor called HER2. This overexpression contributed to the aggressive behaviour of breast cancers in some patients and knowing this has resulted in the development of a new chemotherapeutic agent Herceptin, which inhibits the HER2 receptor. This has led to further improvements in breast cancer survival rates.

Another example of a smart therapy that is already in use relates to the treatment of patients with chronic myleogenous leukaemia (CML) or gastrointestinal stromal tumours (GIST). Many patients with CML or GIST have defects in the ABL or KIT genes which causes specific kinds of marrow cells (in CML) or gut cells (in GIST) to become cancerous. The development of a new drug (Glivec) that targets these defective genes has resulted in 3-5 year survival rates of around 90 per cent for both of these cancer types. It was only 10 years ago that these diseases were essentially incurable. The final example relates to the development of the vaccine against human papillomavirus (HPV) which prevents the development HPV-induced cervical cancer. Once global immunisation programs are complete this vaccine will potentially prevent 250,000 female deaths per year from this virus.

The examples cited above provide evidence that knowledge of the molecular basis for cancer formation has already led to the development of “smart therapies” that prevent cancers or provide long-term survival rates and cures. The use of these therapies is not associated with the same serious side effects associated with cancer chemotherapeutics and hence provides evidence that future “smart therapies” will deliver pain-free cures for cancer in the future.

This article is a summary of a presentation given by Associate Professor Nicholas Saunders to the Brisbane Institute in 2008.