Growth factor-induced proliferative signaling

Growth factor-induced proliferative signaling is a fundamental biological process and a recognized hallmark of cancer characterized by the chronic stimulation of cell division (Hanahan & Weinberg, 2011, Cell). In normal physiology, cells require external growth factors to transition from a quiescent state into an active proliferative cycle, ensuring tissue homeostasis (Lemmon & Schlessinger, 2010, Cell). However, in oncogenic states, this process becomes deregulated through the overproduction of growth ligands, overexpression of receptor tyrosine kinases (RTKs), or constitutive activation of downstream signaling cascades such as the MAPK/ERK and PI3K/Akt pathways (Sever & Brugge, 2015, Cold Spring Harb Perspect Med). Therapeutic strategies targeting this process involve small molecule inhibitors and monoclonal antibodies designed to block receptor-ligand interactions or inhibit the enzymatic activity of intracellular kinases (NIH, National Cancer Institute). Examples of such drugs include EGFR inhibitors like erlotinib and HER2-targeted antibodies like trastuzumab (PubChem). While highly effective in certain malignancies, these therapies often face challenges such as the development of compensatory signaling pathways and acquired resistance. Additionally, because these pathways are also used by normal cells, treatment can lead to side effects in the skin, gut, and other regenerative tissues (StatPearls, Tyrosine Kinase Inhibitors).

Other names

Sustaining proliferative signalingMitogenic signalingGrowth factor signaling pathway

Inhibition of receptor tyrosine kinases (RTKs) or downstream intracellular kinases (e.g., RAS, RAF, MEK, PI3K) to interrupt the transmission of mitogenic signals to the nucleus.