Intrinsic resistance is primarily due to the genetic and epigenetic characteristics of cancer cells. Several factors contribute to this phenomenon, including:
1. Genetic Mutations: Certain mutations in genes, such as those in the TP53, KRAS, or EGFR genes, can make cancer cells inherently resistant to specific drugs. 2. Efflux Pumps: Overexpression of efflux pumps like P-glycoprotein can result in the rapid expulsion of drugs from cancer cells, reducing their intracellular concentration and effectiveness. 3. Cell Cycle Dynamics: Some cancer cells may have alterations in their cell cycle dynamics, making them less susceptible to drugs that target rapidly dividing cells. 4. Microenvironment Factors: The tumor microenvironment, including factors like hypoxia and the presence of stromal cells, can also play a role in intrinsic resistance.
