Since the description of cancer by Hippocrates many centuries ago there has been a vastly growing momentum in fighting this aggressive, often fatal disease. One of the landmark advances in treatment occurred in the late 19th Century when husband and wife Marie and Pierre Curie discovered radiation. This was followed closely by the investigation of mustard gas analogues after the observed side effects of the use of chemical warfare by the Germans in World War II. In the 1940s and 1950s Sidney Fabre undertook ground breaking work with children suffering from acute lymphoblastic leukaemia (ALL) using what is now known as methotrexate and for the first time ever achieved remission in patients suffering from what at the time was thought of as an incurable disease.

Investigations on the effects of methotrexate on solid tumors came along soon after and in the 1960s combination use of chemotherapy was shown to achieve excellent results in patients with various different blood-based cancers. This was closely followed by the advent of adjuvant therapy in both solid tumor and blood-based malignancies, which demonstrated increasing effectiveness in both remission and effective cure of some cancers.

Over the past 50 to 60 years the number of drugs that have been developed to effectively treat different cancers is nothing short of amazing. Drugs such as paclitaxel, docetaxel and cisplatin have changed the face of cancer management. But now the pharma industry is taking treatment to the next level. More and more developments are not looking at pharmacologically attacking the tumor or malignancy, but altering the bodies mechanisms to facilitate the body to beat the cancer itself. Targeted therapies interfere with the signaling mechanisms between cells and have altered the progression of many cancers. Monoclonal antibodies, which were derived from mice initially, have been ‘humanized’ and are now used highly effectively to treat a range of cancers. Monoclonal antibodies can work via various mechanisms such as making cells more susceptible and visible to the immune system, blocking growth factors or effectively starving the tumor cells by restricting vascularization. Some of these treatments have become the most recognized in cancer care such as trastuzumab (Herceptin) for breast cancer and bevacizumab (Avastin) used to treat lung, renal and ovarian cancer to name but a few.

Advances in cancer therapy are so rapid now that it’s not possible to highlight all the recent developments, but there are a few that are creating great debate due to their potential impact on sufferers. One of the ideal mechanisms for beating any disease is to facilitate the body achieving the desired outcome itself and developments within immunotherapy are snowballing at an amazing rate.
Researchers working at the Fred Hutchinson Cancer Research Center in Seattle, WA, recently published results on their work with modified T-cells extracted from patients with non-responsive acute lymphoblastic leukaemia (ALL). T-cells have various different subtypes and normally work in cell-mediated immunity. They have the ability to memorize, identify and attack tumor cells using chimeric antigen receptors (CAR). The CAR receptor has two sticky ends, which give it the ability to adhere to both the T-cell and the tumor cell. Professor Stanley Riddell’s team in Seattle have engineered new CAR T-cells, which are uniform and stable and are able to proliferate. Cells were harvested, modified and then re-introduced into the patient. Ninety percent of recipients went into remission, which is an astounding result. In a further small trial in patients with non-Hodgkin’s lymphoma (chronic lymphocytic leukaemia) over 80% of patients responded to the CAR T-cell treatment with around 50% maintaining the response and remission 18 months later.

Unfortunately, some of the patients in the trials died from a massive immune reaction to the treatment. This cytokine storm can prove fatal, and although the results from the trails are potentially huge in terms of treatment, implications of the potential risks do have to be considered. The evidence shows though that these naturally occurring, modified cells remain in the body for prolonged periods of time therefore the beneficial impact of the therapy could also be expected to be long-term. It does seem that for some reason the CAR T-cell therapies seem to work best in haematological malignancies, but this new research surely must be good news for progress in this area.

On a solid tumor note very recent research in the more aggressive HER2 breast cancer is giving an indication of new treatment programs. Although now treated with trastuzumab (Herceptin) the prognosis of this type of malignancy is typically poorer than with others. A group of researchers at the Institute of Cancer Research in London led by Professor Judith Bliss recently released results of a trial, which used dual therapy of trastuzumab and lapatinib in 257 women with in HER2 tumors 1-3cm in size. The original aim or the investigation was to assess the impact of drug therapy on tumor size between diagnosis and excision of the malignant mass.

After only 11 days of treatment in 11% of the women the tumor had disappeared completely, and a further 17% showed a reduction in size of growth such that they were less than 5mm in diameter. The two drugs work with entirely different mechanisms, and the combination at an early stage has shown some dramatic effects. This new dual therapy has the potential to change the way in which HER2 breast cancer can be managed, however due to the fact that relapse is more common in this specific type of tumor, monitoring must be maintained. Up until now the standard manner of care has been to operate to remove the tumor and then treat with chemotherapy and Herceptin. If the effects of this new treatment regimen could be consistently repeated the avoidance of chemotherapy could be a distinct possibility.

As the pharmacological options for cancer treatment are developing so rapidly, treatment regimens are becoming much more personalized. And as sub types of tumor are categorized the specificity at diagnosis can make all the difference.

Although we haven’t yet beaten cancer, the industry, medics and academia as a whole is working towards making this a disease that’s livable with rather than one of utter gloom and doom, which it has been in the past. These advances are amazing and it will be interesting to see how the outcomes are adopted in to clinical practice. If we keep chipping away at the block, at some point a cure surely has to be uncovered. 

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Adele Graham-King
Contributing Editor

Adele is a design consultant who works in prod- uct development for medical and healthcare ap- plications. Her background is in pharma, and she has a degree in applied physiology.