Cyclin E as a potential therapeutic target in high grade serous ovarian cancer.

Cyclin E1 (CCNE1) gene amplification occurs in approximately 20% of ovarian high grade serous carcinoma (HGSC) and is associated with chemotherapy resistance and, in some studies, overall poor prognosis. The role of cyclin E1 in inducing S phase entry relies upon its interactions with cyclin dependent kinases (CDK), specifically CDK2. Therapies to target cyclin E1-related functions have centered on CDK inhibitors and proteasome inhibitors. While many studies have helped elucidate the functions and regulatory mechanisms of cyclin E1, further research utilizing cyclin E1 as a therapeutic target in ovarian cancer is warranted. This review serves to present the scientific background describing the role and function of cyclin E1 in cancer development and progression, to distinguish cyclin E1-amplified HGSC as a unique subset of ovarian cancer deserving of further therapeutic investigation, and to provide an updated overview on the studies which have utilized cyclin E1 as a target for therapy in ovarian cancer

Cyclin E as a potential therapeutic target in high grade serous ovarian cancer.

Cyclin E1 (CCNE1) gene amplification occurs in approximately 20% of ovarian high grade serous carcinoma (HGSC) and is associated with chemotherapy resistance and, in some studies, overall poor prognosis. The role of cyclin E1 in inducing S phase entry relies upon its interactions with cyclin dependent kinases (CDK), specifically CDK2. Therapies to target cyclin E1-related functions have centered on CDK inhibitors and proteasome inhibitors. While many studies have helped elucidate the functions and regulatory mechanisms of cyclin E1, further research utilizing cyclin E1 as a therapeutic target in ovarian cancer is warranted. This review serves to present the scientific background describing the role and function of cyclin E1 in cancer development and progression, to distinguish cyclin E1-amplified HGSC as a unique subset of ovarian cancer deserving of further therapeutic investigation, and to provide an updated overview on the studies which have utilized cyclin E1 as a target for therapy in ovarian cancer

Functional studies on the role of notch signaling in hydractinia development

The function of Notch signaling was previously studied in two cnidarians, Hydra and Nematostella, representing the lineages Hydrozoa and Anthozoa, respectively. Using pharmacological inhibition in Hydra and a combination of pharmacological and genetic approaches in Nematostella, it was shown in both animals that Notch is required for tentacle morphogenesis and for late stages of stinging cell maturation. Surprisingly, a role for Notch in neural development, which is well documented in bilaterians, was evident in embryonic Nematostella but not in adult Hydra. Adult neurogenesis in the latter seemed to be unaffected by DAFT, a drug that inhibits Notch signaling. To address this apparent discrepancy, we studied the role of Notch in Hydractinia echinata, an additional hydrozoan, in all life stages. Using CRISPR-Cas9 mediated mutagenesis, transgenesis, and pharmacological interference we show that Notch is dispensable for Hydractinia normal neurogenesis in all life stages but is required for the maturation of stinging cells and for tentacle morphogenesis. Our results are consistent with a conserved role for Notch in morphogenesis and nematogenesis across Cnidaria, and a lineage specific loss of Notch dependence in neurogenesis in hydrozoans