Some patients with metastatic lung ,colorectal or pancreatic cancers initially show positive results from EGFP-targeted therapies, however the resistance to targeted therapies eventually develops. In order to make it effective, researchers attempt to understand what related proteins in a signaling network cause resistance of tumors to EGFR inhibitors. With growing knowledge of resistance pathways appear, we obtain a great chance to develop new mechanism-based inhibitors or joint therapies to prevent therapeutic resistance in tumors.
Louis Weiner et al discuss how cancer cells activate a network of specific proteins which evade a molecule from being therapeutically in the issue of Science Signal. Treatment by FDA-approved drugs that are designated to shut down the EGFR tend to be inefficient, partly due to involving of some genes in evading cancer cells. He says the essence of drug resistance is evolutionary pressure to survive, and the only way to treat cancer is to disarm some of key “rescue” genes and proteins. by using a screen technique, investigators identified 61 genes that play some role in anti-EGFR drug resistance.
The concept of oncogene addiction was defined by Weinstein in 2002, which highlights the crucial importance of EGFR to tumor cell survival in lung adenocarcinoma. It means that a cancer cell is dependent of a specific oncogenic signaling pathway. For instance. Drugs that inhibit mutant EGFR such as erlotinib turn off this key pathway and result in tumor cell apoptosis.
A decade later, oncogene-targeted therapies grant a reprieve for patients who are lucky to have been selected driver mutation, and alleviation last years in some cases. For patients with EGFR-mutant lung cancer, tumor responses persist for months which is better than patients without such a mutation.
Cancer researchers and clinicians should realize the importance of perseverance, creativity and collaboration. Whether tumor resistance is defeated using combinations of drugs, immunotherapy, new dosing strategies or an undiscovered approach, patients cannot benefit from novel therapies soon enough.