Cancer – Causes, Symptoms, Diagnosis, Treatment

Cancer, known medically as a malignant neoplasm, is a broad group of various diseases, all involving unregulated cell growth.

Cancer describes a broad group of diseases, all involving unregulated cell growth caused by genetic mutations. Cancers comprise the malignant (having a tendency to become worse) subset of neoplasms —a cell or group of cells that undergo unregulated growth and form a mass of tissue —often referred to as a tumor. A major hallmark of cancers is metastasis, the ability of cancer to spread between tissues and organs within the body.

Non-malignant tumors are referred to as benign; they are typically slow-growing and are often surrounded by a membrane of connective tissue that prevents metastasis. A common example of a benign tumor is a skin mole.

While typically asymptomatic, benign tumors can impact health, usually by impairing organ function through the compression of blood vessels or nerve fibers.

Hallmarks of Cancer

Due to the wide variety of cancerous diseases, six hallmarks are used to group and define cancers:

• Unregulated cell growth and division.
• Continuous growth and division gave contrary signals.
• Avoidance of programmed cell death.
• Unlimited cell division.
• Promoting vascularisation.
• Invasion of tissue and formation of metastases.

Signs and Symptoms

Cancer is typically asymptomatic at onset; its symptoms appear as the tumor grows and invades other tissues. Initial symptoms are typically associated with the loss of organ function at the tumor site.

For example, patients with lung cancer often present with symptoms including breathlessness and chronic cough, but can vary widely between patients. Due to this variation and the association of symptoms with other disorders, an early diagnosis of cancer is often difficult.

As the disease progresses, systemic symptoms such as weight loss, fever, and tiredness can develop. Additionally, symptoms associated with metastasis—such as enlarged lymph nodes, an enlarged liver, or an enlarged spleen—can develop.

Classification

Cancers are classified by the type of cell that the tumor cells resemble with the presumption that this shows the origin of the tumor. These include:

• Carcinoma: Cancers derived from epithelial cells. This group includes many of the most common cancers, particularly in the aged, and include nearly all those developing in the breast, prostate, lung, pancreas, and colon.
• Sarcoma: Cancers arising from connective tissue (i.e., bone, cartilage, fat, nerve), each of which develop from cells originating in the mesenchymal cells outside the bone marrow.
• Lymphoma and leukemia: These two classes of cancer arise from hematopoietic (blood-forming) cells that leave the marrow and tend to mature in the lymph nodes and blood, respectively.
• Germ cell tumor: Cancers derived from pluripotent cells, most often presenting in the testicle or the ovary (seminoma and dysgerminoma, respectively).
• Blastoma: Cancers derived from immature precursor cells or embryonic tissue. These are also most common in children.

Causes of Cancer

Cancers are primarily associated with environmental factors such as smoking, obesity, high alcohol consumption, radiation exposure, and environmental pollutants. However, it is important to note that exposure to these factors merely imparts an increased risk of the development of cancer, rather than ensuring its development.

There is some element of genetic risk in the development of cancers, with some specific subsets having a very high genetic risk component. For example, familial mutations of the BRCA1 and BRCA2 genes are associated with an increased risk of developing breast cancer.

Genetics of Cancer

Cancer is a disease of dysregulated cell proliferation. At the genetic level, cell proliferation can either be promoted or repressed via the expression of key genes; with alteration of these genes, expression or function via mutation, as induced by the factors discussed above, result in dysregulated proliferation.

Affected genes can be divided into two broad categories.

1. Oncogenes are genes that promote cell growth and reproduction, such as the gene MYC.
2. Tumor suppressor genes are genes that inhibit cell division and survival, such as the TP53 gene.

Malignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, changes in multiple genes are required to transform a normal cell into a cancer cell.

Pathway of cancer development: Cancer develops due to mutations in several key genes that control cell proliferation and survival.

Therapies

Cancer therapy varies by patient, tumor type, and location. The most common treatments include:

• Surgery: This is the primary method of treatment for most isolated, solid cancers. It is also typically an important part of making the definitive diagnosis of tumor type and character through biopsies.
• Chemotherapy: In addition to surgery, this has proven useful in a number of different cancer types. Chemotherapy refers to the administration of a toxin that targets rapidly dividing cells and promotes their cell death. It is nonspecific to tumors and it’s effect on other rapidly dividing cells, such as those of the hair follicle, give rise to the side-effects associated with chemotherapy.
• Radiotherapy: Radiation therapy involves the use of ionizing radiation to specifically target a tumor within the body, leading to its death. Radiation is typically used in addition to surgery and/or chemotherapy. For certain types of cancer, such as early head and neck cancer, it may be used alone.

Cell Signaling and Cell Death

When a cell is damaged, unnecessary, or dangerous to an organism, a cell can initiate the mechanism for cell death known as apoptosis.

Apoptosis

When a cell is damaged, superfluous, or potentially dangerous to an organism, a cell can initiate a mechanism to trigger programmed cell death, or apoptosis. Apoptosis allows a cell to die in a controlled manner that prevents the release of potentially damaging molecules from inside the cell.

Internal Signaling

There are many internal checkpoints that monitor a cell’s health; if abnormalities are observed, a cell can spontaneously initiate the process of apoptosis. However, in some cases such as a viral infection or uncontrolled cell division due to cancer, the cell’s normal checks and balances fail.

External Signaling

Apoptosis: The histological section of a foot of a 15-day-old mouse embryo, visualized using light microscopy, reveals areas of tissue between the toes which apoptosis will eliminate before the mouse reaches its full gestational age at 27 days.

External signaling can also initiate apoptosis. For example, most normal animal cells have receptors that interact with the extracellular matrix, a network of glycoproteins that provides structural support for cells in an organism. The binding of cellular receptors to the extracellular matrix initiates a signaling cascade within the cell. However, if the cell moves away from the extracellular matrix, the signaling ceases, and the cell undergoes apoptosis. This system keeps cells from traveling through the body and proliferating out of control, as happens with tumor cells that metastasize.

Another example of external signaling that leads to apoptosis occurs in T-cell development. T-cells are immune cells that bind to foreign macromolecules and particles, targeting them for destruction by the immune system. Normally, T-cells do not target “self” proteins (those of their own organism), a process that can lead to autoimmune diseases. In order to develop the ability to discriminate between self and non-self, immature T-cells undergo screening to determine whether they bind to so-called self-proteins. If the T-cell receptor binds to self-proteins, the cell initiates apoptosis to remove the potentially dangerous cell.

Apoptosis and Embryos

Apoptosis is also essential for normal embryological development. Invertebrates, for example, early stages of development include the formation of web-like tissue between individual fingers and toes. During the course of normal development, these unnecessary cells must be eliminated, enabling fully separated fingers and toes to form. A cell signaling mechanism triggers apoptosis, which destroys the cells between the developing digits.