**3. Cancer**

According to the World Health Organization, "cancer is a generic term for a large group of diseases characterized by the growth of abnormal cells beyond their usual boundaries that can then invade adjoining parts of the body and/or spread to other organs" [19]. Cancer involves carcinogenesis, which means cancer development; more accuracy, carcinogenesis was first defined by Hecker in 1976 as the "generation of neoplasia" [20]. Neoplasia is an abnormal growth not coordinated with the surrounding tissue [21].

Cancer is initiated via carcinogens in the environment that induce mutations in critical genes, and these mutations direct the cell in which they occur, as well as all of its progeny cells, to grow abnormally. The result of this abnormal growth appears years later as a tumor [21].

Cancer has been traditionally classified in three ways: by the type of tissue in which cancer originates (histological type), by the primary body site, and by the staging (see Figure 4) [19,21].

Histologically, cancer is classified as carcinoma, sarcoma, myeloma, leukemia, and lymphoma [22,23]. Carcinoma refers to a malignant neoplasm of epithelial origin, skin, and tissues that line or cover internal organs. There are two subtypes, adenocarcinoma, which develops in an organ or gland, and squamous cell carcinoma, which originates in the squamous epithelium [23].

Sarcoma refers to cancer that originates in supportive and connective tissues such as the bones, tendons, cartilage, muscle, and fat [22]. Myeloma is cancer that originates in the plasma cells of the bone marrow. Leukemias are also presented in the bone marrow, but this cancer type is associated with the overproduction of immature white blood cells. Leukemia also affects red blood cells and can cause poor blood clotting and fatigue due to anemia [23].

**Figure 4.** Traditionally cancer classification, histology, primary body site and staging.

Lymphomas develop in the glands or nodes of the lymphatic system—a network of vessels, nodes, and organs (specifically the spleen, tonsils, and thymus) that purify bodily fluids and produce infection-fighting white blood cells, or lymphocytes [22,23].

The body site classification is more familiar to patients, and it refers to the anatomical site at which the cancer appears, for instance, the brain, colorectal tissues, skin, or breast, among others. Finally, staging refers to the process of determining the size of cancer in the body and its localization [23]. To assess the staging of cancer, several diagnostic tests are required (X-rays, biopsies, and ultrasound, among others). In Stage 0, abnormal cells are present but have not spread to nearby tissue [24]; in Stages I, II, and III, cancer is present (the higher stage number, the larger the tumor and the more it has spread into surrounding tissues); and in stage IV, cancer has spread to distant parts of the body (metastasis) [23].

There are also other systems more precise from the medical point of view, for instance, the tumor-node-metastasis (TNM) system that is suggested by The American Joint Committee on Cancer. The TNM is updated periodically, based on advances in the understanding of cancer prognosis, to remain current and relevant for clinical practice; this manual is also described for every anatomical site [23,25].

Recently, there have been other efforts to generate an integrated system to classify cancer [26]. Cancer cells are classified using the cell morphology, leaving behind the functional attributes of these cancer cells. Using techniques in biology based on genomics, transcriptomics, and proteomics, scientists can model the attributes of cancer stem cells and their potential contribution to treatment responses and metastases [26–30].
