Lineage plasticity, the switching of cells from one lineage to another, has been recognized as a cardinal property essential for embryonic development, tissue repair and homeostasis. However, such a highly regulated process goes awry when
cancer cells exploit this inherent ability to their advantage, resulting in
tumorigenesis, relapse,
metastasis and
therapy resistance. In this review, we summarize our current understanding on the role of lineage plasticity in
tumor progression and therapeutic resistance in multiple
cancers. Lineage plasticity can be triggered by treatment itself and is reported across various solid as well as liquid
tumors. Here, we focus on the importance of lineage switching in
tumor progression and therapeutic resistance of solid
tumors such as the prostate, lung, hepatocellular and
colorectal carcinoma and the myeloid and lymphoid lineage switch observed in
leukemias. Besides this, we also discuss the role of epithelial-mesenchymal transition (EMT) in facilitating the lineage switch in biphasic
cancers such as aggressive
carcinosarcomas. We also discuss the mechanisms involved, current therapeutic approaches and challenges that lie ahead in taming the scourge of lineage plasticity in
cancer.