Cancer: Advances in the treatment of Melanoma

Cancer is a group of diseases characterized by a double fault: A «real» alteration in the control of cell division, becoming independent tumor cells of normal controls existing in a healthy body, and a «potential» alteration in the mechanisms that control the location temporo-space of the cells within the body, generating the potential to travel to remote site or organ of origin of the cell tumor (metastases). Why we talk about a real and potential alteration? Real alteration because the uncontrolled cell multiplication is the primary basis or cancer. without this chaos the disease would not exist.

Potential alteration because many tumors are detected when they have not yet migrated or «gone» out of its place of origin, therefore it is a demonstration that although it may occur if the tumor is left to their natural evolution it may not even be present at the time of detection of a tumor.
Now it is possible to say that cancer is a genetic disease, this is in the sense that it is always determined by one or more gene mutations (changes in its composition) that regulate cell division and location temporo-spatial cells in the body. The gene whose mutation predisposes to cancer are called oncogenes and / or suppressor genes. The vast majority of mutations that determine the cancer occur in somatic cells (Not present in the germ cells such as sperm and ova). This means that more than 95% of cancers there is no hereditary predisposition. Once these changes have occurred, there is what we call «avalanche effect»: original mutations determine new mutations. These determine greater aggressiveness and ability to generate metastases and eventually, resistance to chemotherapeutic agents and spread of tumor potency over time. This determines that, despite the progress made in the diagnosis and cancer treatment, the problem remains serious.

Is it possible to avoid the appearance of cancer? In some cases yes, and in these cases it is advisable to take preventive behaviors such as avoiding smoking (tobacco is linked to lung cancer), avoid overexposure to the sun (Such exposure is linked to the onset of melanoma, a skin cancer extremely aggressive). However, in the majority of tumors is not possible to prevent its occurrence. Therefore, we must build «protectors of avalanches». The protectors of natural avalanches are elements of the body’s immune system, Ie «defenses» (antibodies, white blood cells). There are now evidence showing that in the first instance, these elements can remove tumors emerging. However, in many cases the tumor finally achieves conquer and develop. The crucial question then is: a person who «spontaneously» can not reject the tumor, is it possible to induce a rejection of the same? It is working for several years on the design of Anti-tumor vaccines. In oncology, vaccines tested so far are called «therapeutic», since they are used once the disease has been declared, unlike the «preventive vaccines» in infectious diseases and serve to «prevent» a determined infection. The newly approved vaccine against human papilloma virus (HPV), that predisposes to cancer of cervix, it is, however, an example of preventive vaccine, as it tries to prevent the emergence of such a cancer. In our laboratory we have started already 15 years ago with the study of therapeutic vaccines in melanoma (a type of skin cancer). Why? Melanoma is of great medical significance at the present time since it is the tumor incidence (new cases) is increasing faster, calculated that 1 of every 67 born childrens will get it in the course of their lives. It is the most common cancer between 15 and 44 years and only in our country are detected each year 5,000 new cases. These patients lie especially in the early diagnosis can be done in this regard; then, there are less valid therapeutic options.

In addition to environmental risk factors, such as exposure to sunlight, there are personal characteristics of likely predisposing genetic control, like skin pigmentation, the total number of moles (nevos) and the presence of atypical moles (dysplastic nevos). In other words, there is a huge swathe of the population with increased susceptibility to the development of melanoma either characteristics of genetic predisposition or environmental factors.

Early detection and surgical removal are important tools in the treatment of melanoma and they are a determining factor for the current increase in the mortality curve (number of deaths per year) is less than the incidence curve (number of new cases per year). The primary cutaneous melanoma, namely the rise and detected in the skin, can raise an immune response as inferred by the intense reaction lymphoid (lymphocytes) that usually accompany such injuries. In contrast to this, this capacity is lost heavily on metastases. If we consider the current schemes of therapeutic vaccination where are treated patients with illness, the main objective is to achieve the disease-free period an immunization effective patient generating an immune response of sufficient magnitude to neutralize the further growth and spread of melanoma cells that could have produced metastases.

What elements or antigens are used to this kind of vaccination? Our approach is that the use of a single element (purified monoantigen) does not appear to be sufficient since it allows the emergence of resistant variants of tumor cells that does not express this antigen. To paraphrase what happened with chemotherapy where «polychemotherapy» has been generally more effective than «monochemotherapy», in our case, the «poli-antigen-vaccine» would be more effective than the «mono-antigen-vaccine». What better source of antigens from the same cell tumor completely, once radiated to remove their ability gearbox? Indeed, the use of whole cell «sample» the immune system a wide variety of antigens. Our research group has carried out clinical Test of investigation in patients with melanoma using these vaccines with excellent results and is currently facing the implementation of a new Clinical test in more advanced stage in the process of Clinical Research (Phase II / III) in about 108 patients with melanoma that, if successful, could lead to approval of the vaccine as medicine.
Dr. Jose Mordoh
Director of Oncologic Investigation Center – FUCA
Alexander Fleming Institute