By: Prof. Abraham Kuten, Director, Department of Oncology, Rambam Medical Center
Dr. Hadassah Goldberg, Director, Breast Cancer Unit, Institute of Oncology, Rambam Medical
Center

Medicine is changing. The new direction in medicine, in general, and in cancer treatment, in particular, is “personalized therapy”. To appreciate the depth of this change, one must grasp the two key principles underlying current pharmaceutical treatments.
One principle is statistical. The medical world we know acts on the basis of statistical data. Regarding every treatment, controlled studies determnine what percentage of patients will achieve the desired response, and the frequency of side effects associated with the treatment. If you are on the good side of the statistics - you win. If not - you lose. Usually, this works.
The second principle is based on trial and error. Current practices do not enable doctors to predict whether treatment with a certain drug will yield the desired response. The physician decides, according to  the patient’s response and side effects, whether e treatment should be continued, and at what dosages.

The drug is not always suitable, and the dosage not always optimal.
As a result, the patient may undergo unnecessary suffering, and in extreme cases, irreversible damage. This is in addition to the financial cost of the treatment, and the heavy fiscal burden on the public budget.

The need to determine the correct therapy is particularly important when treating malignant disease. Treatments such as chemotherapy or radiationdetermine, to a large extent, the patient’s chances of recovery, and often entail significant side effects.
The journey towards understanding the human genome led to deciphering the structure and function of DNA. This, along with studies aimed at understanding the cellular biological processes occurring during the development of a malignant tumor, opened new fronts in  the war on cancer.

Genetic fingerprints

One of the new fields that developed according to the deciphered human genome is called “pharmacogenetics”. Put simply, this means the use of drugs according to the personal genetic structure of the patient or the tumor. Application of this technology is still in the fledgling stage, but it looks promising.

One of the examples of  the use of pharmacogenetics is related to chemotherapy for breast cancer. Chemotherapy for women who underwent breast tumor resection is a very important stage in treating the disease. According to the traditional approach, however,  patients whose tumors had similar characteristics received the same chemotherapy.

The human genome project has led also to the development of a variety of new technologies and diagnostic tools in the field of the genetics. It’s become clear that breast cancer is not a uniform disease, and no two tumors are identical. Every cancerous growth has its own specific genetic features, and breast cancer differs from woman to woman. Tumors do not behave the same way, and respond differently to chemotherapy, even if the clinical findings are similar.

The use of modern technologies currently enables a more accurate determination of the chances of cure for each woman. This is achieved by identifying the level of expression of various genes in the tumor cells, or, as it is called, identifying the “genetic fingerprint” of the tumor. Based on this information, it is possible to determine the degree to which chemotherapy needs to be administered for each patient.

One of the new tests, considered a breakthrough in this field, is called “OncotypeDX”. This is a laboratory test performed on a sample of tumor tissue (biopsy), and identifies the degree of expression of various genes in the tumor. Currently, based on this test, it is possible to establish which patients will most probably not develop recurrent cancer or metastases. They can thus  avoid unnecessary chemotherapy.

Targeted therapies

During the development of a malignant tumor, various genetic and molecular changes occur at the cellular level. Many years of researching these changes now enables the identification of characteristics specific to tumor cells, distinguishing them from cells of healthy tissue. Based on this variance, it is currently possible to develop treatments that will cause fatal damage to cancerous cells, with minimal harm to healthy tissue. This type of treatment will not have dosage limitations, and toxicity is expected to be insignificant. These medications, called “targeted therapies”, or “biological drugs”, are effective only in those tumors bearing the specific characteristic at which the therapy is targeted.

To this point, several drugs have been developed on the basis of this principle, such as the agents herceptin and lapatinib, targeted against the HER-2 receptor, which is overexpressed in some breast tumors. These agents are just the tip of the iceberg in the field of targeted biological drugs, which specifically attack diseased cells, without damaging the body’s healthy systems.

Scientific progress is similar to stones thrown into the water - one big leap forward, followed by many, many waves of field work all around. Herceptin and lapatinib represent the huge leap forward, the beginning of the biological era in cancer therapy.

Minimal treatment for maximal effect

It doesn’t stop here. Every doctor seeks to administer the minimal treatment to achieve the maximal effect. Identification of congenital genetic features of healthy tissues may also help in the future to reach this goal, and to “tailor” the most appropriate treatment for each individual patient. For some genes, there is slight variance from person to person, which is not manifested in everyday life. Under stress conditions, however, such as radiation treatment, this variance dictates the degree of toxicity caused to healthy tissue. For example, for patients whose genetic features predict extensive damage to the healthy tissue, radiation therapy can be waived, and an alternative, no-less-effective treatment can be chosen.

This type of medicine is highly accurate.  It  enables us to provide a specific treatment for each patient, based on his genetic characteristics and those of his tumor.
Through personalized medicine, each of us may one day carry a personal magnetic card imprinted with our “genetic fingerprint”. This card will guide the doctor to the most efficient treatment for us:that which will do the best job, with the least side effects.