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  • Writer's pictureDr Edin Hamzić

What is clonal evolution?

How Does Cancer Happen?

From what we know, cancer does not happen suddenly with a somatic mutation happening that might lead to the conversion of a normal cell into cancer cells. On the contrary, cancer happens as a result of successive rounds of mutations and consecutive selection of mutated cells that finally leads to progressive, I repeat progressive, conversion of normal human cells into cancer cells.

The scientific studies so far support the thesis that cancer is a multistep process, and it has been shown that carcinomas happen as a result of a minimum of five or more genetic mutations. Another study also showed that a minimum of four distinct pathways must be disrupted to convert a normal cell into a tumor cell and those are:

  1. the mitogen-response pathway

  2. the telomere maintenance pathway

  3. the retinoblastoma pathway, and

  4. the p53 pathway.

An important aspect of the onset of cancer is that genomic integrity is disrupted, which makes cells unable to perform DNA repair and prevent malignant transformations. Genomic integrity and stability are maintained by complex systems of DNA monitoring and repair enzymes, and as I already wrote, disruption of one of these systems enables the rate of mutations that are large enough for the transformation of normal cells into malignant.

What Is Clonal Evolution?

Once cancer arises, cancer cells continue to go through clonal evolution. Clonal evolution is a process that occurs during the development and progression of cancer, and it corresponds to the gradual accumulation of genetic mutations in cancer cells over time, which can lead to the development of new subpopulations of cancer cells with distinct genetic characteristics.

Cancer cells can undergo various genetic alterations during clonal evolution, including genetic mutations, deletions, amplifications, and rearrangements. These genetic changes can affect the function of genes and alter the behavior of cancer cells, allowing them to evade the body's normal defenses and continue to grow and divide uncontrollably.

Clonal evolution results in the acquisition of capabilities by cancer cells that underlie the malignant transformation process:

  1. Self-sufficiency in growth signals

  2. Insensitivity to antigrowth signals

  3. Evasion of apoptosis (if interested, you can check my short post about apoptosis here)

  4. Evasion of senescence

  5. Ability to induce and sustain angiogenesis, and

  6. Ability to invade and metastasize.

Clonal evolution can occur at different stages of cancer development and can significantly impact the progression and treatment of cancer. For example, specific genetic changes may make cancer cells more resistant to chemotherapy or other treatments or more aggressive and more likely to spread to other body parts.


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