PLK1, A Potential Target for Cancer Therapy

Abstract

Polo-like kinase 1 (PLK1) plays an important role in the initiation, maintenance, and completion of mitosis. Dysfunction of PLK1 may promote cancerous transformation and drive its progression. PLK1 overexpression has been found in a variety of human cancers and was associated with poor prognoses in cancers. Many studies have showed that inhibition of PLK1 could lead to death of cancer cells by interfering with multiple stages of mitosis. Thus, PLK1 is expected to be a potential target for cancer therapy. In this article, we examined PLK1’s structural characteristics, its regulatory roles in cell mitosis, PLK1 expression, and its association with survival prognoses of cancer patients in a wide variety of cancer types, PLK1 interaction networks, and PLK1 inhibitors under investigation. Finally, we discussed the key issues in the development of PLK1-targeted cancer therapy.

Response of head and neck epithelial cells to a DNA damage‐differentiation checkpoint involving polyploidization

“…To more specifically test for the response to mitotic checkpoints, we inhibited AurBK or PLK1 by use of chemical inhibitors. These molecules are currently being tested as anticancer targets for their critical role in mitosis and involvement in the mitosis checkpoints . As shown in Figure and Supporting Information Figure S4, inhibition of these molecules induced a cell accumulation in mitosis and a great increase of cell size (phase contrast and light scattering), terminal differentiation (by means of involucrin expression) and polyploidy in cells from trachea, oral mucosa, and pharynx.…”

Integrative molecular profiling identifies a novel cluster of estrogen receptor‐positive breast cancer in very young women

“…Group A was characterized by IGF1R, and ER‐alpha pathways' activation and PLK1 downregulation ( P < 5.0 × 10 −4 ). PLK1 (polo like kinase 1), a key regulator of mitosis, cooperates with ER‐dependent gene transcription, and its overexpression in cancer cells is associated with poor prognosis . PLK1 downregulation enriched in group A seems to be associated with good‐prognosis, high proportion of stromal cells and low chromosome instability ( P = 7.513 × 10 −5 , t test; FC = 2.88; Figure ) …”

Phase I dose‐escalation trial investigating volasertib as monotherapy or in combination with cytarabine in patients with relapsed/refractory acute myeloid leukaemia

“…Non‐microtubule components of mitosis, including polo‐like kinase 1 (PLK1), are required for complete cell division and have emerged as promising targets for cancer therapy. Human PLK1 is highly expressed in malignant lymphomas and acute myeloid leukaemia (AML), and elevated PLK1 is associated with poor prognosis in several cancer types (Liu et al , ).…”