Breast Cancer - Needs

Cells that grow uncontrollably often become cancerous [Harvard University].

The process by which our cells grow and multiply (called cell division) is normally tightly controlled. In embryos and young children, cell division is primarily needed for growth. However, its main role in adults is to repair and replace old cells.

Cell division is a very complex process, and it involves a very ordered sequence of events. Cancer occurs when a cell breaks free from normal constraints and starts multiplying uncontrollably. Tens, if not hundreds, of molecules are involved in cell division, and many of these have been implicated in cancer.

Cyclin D1
A study has revealed that one of these molecules, cyclin D1, is frequently found in very high amounts in breast cancer. It has now been demonstrated that the presence of too much cyclin D1 distinguishes malignant breast cancers (that are likely to grow and spread) from pre-malignant abnormal breast tissue, which is much less dangerous. Proof of principle has come from the breeding of mice that over-produce this cyclin in their mammary glands: they are prone to a type of cancer known as mammary adenocarcinomas.

p53
p53 belongs to a family of genes called the ‘tumour suppressors’. As their name suggests, these genes protect cells from becoming cancerous. p53 has been intensely studied, as it is altered in the majority of human cancers. This gene has been described as the ‘guardian of the genome’ because it scours the genetic material (the DNA) looking for faults. If it finds defects in the DNA, it will tell the cell to stop and repair them. However, if the faults are too serious to be repaired, p53 will trigger the cell to commit suicide. If p53 does not do its job, the damaged DNA will go unnoticed, and the cell may eventually become cancerous. When this gene was first discovered, scientists thought that it might actually be implicated in causing cancer. However, mice that lack p53 are extremely susceptible to cancer and thus its role as a tumour suppressor was confirmed. Now, the replacement of defective copies of p53 in cancer cells is one of the key areas of gene therapy research.

Tailoring the treatment of patients
An exciting development in recent years is the advent of technologies that allow scientists to study the thousands of genes present in cells and tissues in a single experiment. Using this technology, researchers can look for the genetic hallmarks of particular cancers. They can also look for specific genetic faults that might determine the cancer’s sensitivity to certain forms of treatment, or the aggressiveness of the disease. This information should eventually help doctors to tailor their patients’ treatment according to the genetic defects present in their cancer. Thus, the patient receives the treatment that is most likely to work for them.

Vaccine Research
A research group in London is aiming to develop a vaccine based on one of the molecules that distinguishes breast cancer cells from normal cells. By taking this approach they hope to make the patient’s immune system recognize and destroy the cancerous cells. To carry out a clinical study more than 900 women with advanced breast cancer were recruited. The vaccine was given randomly to women in each of two treatment groups: those who were having either chemotherapy or chemotherapy and hormone treatment. However, many in the chemotherapy-only group pulled out at twelve weeks as their cancer had returned. Only one subgroup had a statistically relevant change in survival time. It now seems that a longer time frame is needed to evaluate a vaccine’s true potential – as it takes 18 weeks to get high antibody levels - and that its administration should be done alongside the other treatment regimes, which include hormone therapy. But, the real difficulty will come later: in evaluating the effectiveness of a vaccine to prevent breast cancer. A better animal model would provide clinicians with a confidence of testing a vaccine on healthy individuals instead of trying to treat women with advanced disease where the benefits will always be limited. The availability of such a model, e.g. a transgenic mouse, will allow scientists to do the studies that can’t be done in patients. These include immunizing the animal and then giving them cancerous cells to see if they can destroy them.

The search for new cancer treatments must continue and researchers are now investigating many innovative ways of targeting cancer. For example, in order to grow beyond 1-2mm in size, a tumour must develop its own blood supply. Thus, some scientists are investigating this process and designing treatments that will stop blood vessel formation. Other research is based around modifying existing drugs, to increase their effectiveness or reduce side effects. Combination therapies, where several agents are used in conjunction with each other, are also being tested, as is the timing of chemo- and radiotherapies. By law, all of these approaches will at some stage need to be tested on laboratory animals before being investigated in patients in clinical trials. The discovery of new treatments and their benefits to patients suffering from this frightening disease emphasise the importance of such work.

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