There are more than 3,7 million scientific publications on cancer. It is a diverse field with studies on drug development, metastasis, malignancy, tumor evolution, cancer genetics, immune response, etc. All important aspects of a disease that increases each year. But what is a tumor cell?
Tumor cells are cells originated from a normal tissue/organ, which are reprogrammed through the progressive accumulation of mutations in their genomes. These cells no longer respond to many of the signals that control cellular growth and death, diverging from normalcy. These mutations give tumor cells some “advantages” in the competition for resources (oxygen, nutrients, space, etc). The accumulation gathered of these competitive properties will determine the tumor progression.
It is important to note that there is no one single cause for cancer, it is a multifactorial disease. The factors involved may be inheritance, some genetic disorders, epigenetic (genetic modifications that do not affect the gene sequence itself), environmental, lifestyle, exposure to certain viruses, etc. But regardless the cause, during this transforming process, almost all cancer cells have altered their:
Growth-promoting genes: they control the normal growth of cells.
Tumor suppressor genes: they suppress cell proliferation or the signals needed for cell death.
DNA repair genes: they help recognize errors when DNA is copied to make a new cell. If these genes are not working properly, the mutation rate increases.
In addition, tumors contain heterogeneous cell populations with diverse biological characteristics. The challenge is to understand this heterogeneity and to be able to adapt diagnosis and treatments according to this variability.
Cancer by numbers
Cancer is a devastating and high incidence disease with clinical, social and economic consequences. The risk of developing cancer in a population from 0 to 74 years is 20.2% (22.4% for men and 18.2% for women) with a death risk of 10.6% (12.7% for men and 8.7% for women).
In 2018, 18 million new cases were diagnosed. Currently, lung (2.09 million cases), breast (2.09 million cases) and prostate (1.28 million cases) cancers are the most common.
In terms of mortality, cancer is the second leading cause of death in the world (8.97 million deaths in 2016), surpassed only by ischemic heart disease. However, it is estimated to become the leading death cause by 2060 (~18.63 million deaths). When analyzed by gender, lung cancer – for men – and breast cancer – for women – are those with the highest mortality. In contrast, prostate and thyroid cancers are those with the best prognosis, with a survival of 5 years ~100%.
Breast cancer is the most common cancer (13%) for women between 15-49 years. A particularly aggressive one among them, is the Triple Negative Breast Cancer (TNBC), which represents approximately 10-20% of the cases. The triple negative tumor is defined by the lack 3 receptors (cellular proteins): 2 hormonal receptors (estrogen and progesterone receptors) and the lack of amplification/overexpression of the human epidermal growth factor receptor 2 (HER2). Due to the absence of specific therapeutic targets (estrogen, progesterone and HER2 receptors), the main treatment for TNBC is chemotherapy, however, the results are limited. This subtype of cancer is characterized by a younger age of onset, a high risk of recurrence after surgery, an increased risk of visceral metastasis, having limited treatment options and, consequently, a poor prognosis (outcome). The poorer prognosis in TNBC is explained by early recurrence rates of 10–15% per year for the first several years after initial surgery, compared to 3–5% per year in estrogen receptor-positive and progesterone receptor-positive breast cancer, which can recur decades after diagnosis. For a TNBC patient with distal cancer (metastasis) the prognosis is around 11% of 5-year relative survival rate. But the outlook could be improved with new therapies.
In recent years, overall survival of advanced TNBC has not significantly improved, and patient survival is significantly shorter than that of other breast cancer subtypes. During cancer progression, tumor cells create a microenvironment where the check points for malignant cells are evaded and the immune response is suppressed allowing tumor progression. However, some medical trials using immunotherapies, in which the immune system itself is strengthened to recognize and fight the tumor cells, seem have positives results, bringing hope to these patients.
In this scenario, it is essential to identify new strategies and specific therapeutic targets for this type of cancer.