Cancer

What is cancer...

Cancer is not one disease but a complex group of diseases that share a profound dysregulation of cell proliferation.

The word “CANCER” comes from Latin and means crab. This designation was given since the malignant tumor mass has projections that stubbornly grab everything like a crab.

The term cancer, therefore, refers to malignant tumors, or more correctly to neoplasms.

Neoplasm is an abnormal mass of tissue whose growth exceeds normal tissue and occurs in an uncoordinated way like normal tissue and persists even after the cessation of the stimulus that triggered its development.

Cancer incidence

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. The most common in 2020 (in terms of new cases of cancer) were:

• breast (2.26 million cases)

• lung (2.21 million cases)

• colon and rectum (1.93 million cases)

• prostate (1.41 million cases)

• skin (non-melanoma) (1.20 million cases)

• stomach (1.09 million cases)

The most common causes of cancer death in 2020 were:

• lung (1.80 million deaths)

• colon and rectum (935 000 deaths)

• liver (830 000 deaths)

• stomach (769 000 deaths)

• breast (685 000 deaths)

How does a tumor/neoplasm cell behave?

Tumor/neoplastic cells must develop defense mechanisms that include changing their metabolism in order to promote their growth, survival, proliferation, and long-term maintenance.

The researcher, Otto Warburg, evaluated the cellular respiration of tumor/neoplastic cells and found that they prefer to metabolize glucose into lactate, even in the presence of oxygen which results in lower ATP production. This phenomenon is known as the Warburg effect.

Several theories over the years have been proposed to explain why tumor/neoplastic cells prefer to perform aerobic glycolysis, however, there is no absolute certainty.

A reasonable hypothesis for the Warburg effect is faster ATP synthesis. If we compare the yield of ATP per unit of glucose, aerobic glycolysis is an inefficient means of generating ATP compared to the amount obtained by mitochondrial respiration. However, the rate of glucose metabolism through aerobic glycolysis is greater, such that the production of lactate from glucose occurs 10 to 100 times faster than the complete oxidation of glucose in the mitochondria. Therefore, the amount of ATP synthesized over a while is comparable when either form of glucose metabolism is used.

This and other plausible theories for the Warburg effect functions are summarized in the schematic below.

With the Warburg effect, we quickly realize that at least one thing is certain, tumor/neoplastic cells produce large amounts of lactate. What is the advantage of this large production of lactate?

• Lactate can be used as an alternative energy source

• Lactate will leave the cells and promote acidification of the surrounding environment, and in turn, this acidification has beneficial effects on the tumor cell

  • Induces invasion and metastization

  • Inhibits the anti-tumor immune response

  • Promotes resistance to therapy

How to distinguish between benign and malignant neoplasms?

Benign tumor/neoplasm

• When its macroscopic and microscopic characteristics are relatively innocent, ie the tumor remains localized, does not spread to other parts of the body, and can be surgically removed. The prognosis is usually good, although it can trigger other illnesses.

Tumor/malignant neoplasm

• Are collectively referred to as cancer

• It has the ability to invade and destroy adjacent structures and metastasize from a distance

• They can cause death. However, not all-cause death and there have been great therapeutic achievements.

Nomenclature of the most common forms of tumors/neoplasms according to their origin

Cancer Hallmarks

Cancer hallmarks are biological characteristics that are acquired during tumor development, and it is these hallmarks that are used as therapeutic targets.

Bibliography

• Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer; 2020 (https://gco.iarc.fr/today, accessed September 2021).

• Kumar, V., Abbas, A., & Aster, J. (2020). Robbins and Cotran Pathologic Basis of Disease (10th ed.). Elsevier Health Sciences.

• Liberti, M. V, & Locasale, J. W. (2016). The Warburg Effect: How Does it Benefit Cancer Cells? (vol 41, pg 211, 2016). Trends in Biochemical Sciences, 41(3, SI), 287. https://doi.org/10.1016/j.tibs.2015.12.001.

• https://www.who.int/news-room/fact-sheets/detail/cancer [13/09/2021]

• https://www.verywellhealth.com/what-does-malignant-and-benign-mean-514240 [17/09/2021]

• https://www.cell.com/cell/fulltext/S0092-8674(21)01101-6 [07/10/2021]