Question

Why is a mutation in a signaling pathway not sufficient to create a cancer cell.

Answer 1

Most tumors arise as a consequence of genetic alterations to cellular genes, which may be inherited or arise spontaneously—for example, as a result of DNA damage induced by environmental carcinogens or mutations arising from replication errors.

These alterations confer a selective advantage to the cells, which together with changes in the microenvironment, promote tumor growth and progression.

Some are gain-of-function mutations, producing so-called oncogenes that drive tumor formation. Others inactivate tumor suppressor genes that normally ensure that cells do not proliferate inappropriately or survive outside their normal niche.

Oncogenic mutations can cause the affected genes to be overexpressed (e.g., gene amplification) or produce mutated proteins whose activity is dysregulated (e.g., point mutations, truncations, and fusions).

Deletions and other mutations can inactivate negative regulators that normally function as tumor suppressors. One of the most commonly mutated genes in cancer is the tumor suppressor p53, the so-called guardian of the genome.

It is important to recognize that deregulated synthesis of growth factors themselves plays an important role in many cancers.

Inappropriate synthesis of growth factors by cells expressing the appropriate receptor can generate an autocrine loop driving signaling.