Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive morphological and molecular changes to become more aggressive and malignant in its  character.

Cancer begins as a single genetic change in a healthy cell, and with time, the progenies of that cell continue to proliferate and pass on the mutation to all the daughter cells.  The genome of these mutant cells becomes increasingly unstable, allowing more mutations to accumulate.

For instance, in the initial stages of Chronic Myelogenous Leukemia or CML, the mutant cells exhibit a chromosomal aberration called the Philadelphia chromosome, which is formed by a reciprocal translocation, where the parts of chromosomes 22 and 9 swap places.

This creates a fusion protein BCR-ABL1 that helps cells  increase the cell division rates, escape terminal differentiation, and avoid apoptosis, resulting in the accumulation of abnormal cells.

As the tumor progresses, the tumor cells stimulate the formation of new blood vessels around them by a process called angiogenesis.

These new blood vessels supply the cancer cells with oxygen, nutrients, and growth factors for rapid growth and proliferation. They also help the cancer cells to disseminate and travel to distant parts of the body and metastasize.

The parallel progression model best explains the tumor progression. According to this model, the breast cancer cells from the primary tumor, which is as small as 1 - 4 mm, can start to disseminate to distant organs and seed new tumors.

For the next 6 - 12 years, these seeds develop into secondary tumors in a parallel manner, each acquiring unique mutations at much faster rates. Such random mutations increase the chance of acquiring resistance to cancer treatment, jeopardizing the patients’ life.