Enhancing Efficacy of Cancer Therapeutics by Targeting Wee1 Kinase

Suhani, Sabrina (2020) Enhancing Efficacy of Cancer Therapeutics by Targeting Wee1 Kinase. Master's Thesis / Essay, Biomedical Sciences.

Preview	Text mBMS_2020_SuhaniS.pdf Download (894kB) | Preview
	Text toestemming.pdf Restricted to Registered users only Download (96kB)

Abstract

Wee1 kinase is a key regulator of G2/M cell cycle checkpoint that prevents cellular entry into mitosis in response to DNA damage. Cancer cells often have deficient G1/S checkpoint, as such, they cannot repair the damaged DNA in G1 arrest and largely depend on G2 arrest for DNA repair. Preclinical studies have evaluated the overexpression of Wee1 in many cancer types and its role in stabilization of replication fork, making it an oncogenic driver, which supports the validity of Wee1 inhibition as a therapeutic target in cancer. Inhibition of Wee1 provides a promising strategy in cancer therapy in combination with various DNA-damaging agents; especially when cancer cells have deficient p53 signaling, as mitotic catastrophe results from entry of cells into mitosis with unrepaired DNA. Response of cancer cells to Wee1 inhibition has been evaluated in various cancer types with evidence of some acquired resistance, however, mechanisms have been identified to rescue the G2 abrogation by Wee1 inhibition. Clinical studies have showed promising antitumor activity of Wee1 inhibitor as potentiator of cytotoxicity by chemotherapeutic agents in patients with advanced stage cancer. This article summarizes the function and regulation Wee1 inhibitors and their potential to be used in cancer therapy alone or in combination with other drugs.

Item Type:	Thesis (Master's Thesis / Essay)
Supervisor name:	Jong, S. de
Degree programme:	Biomedical Sciences
Thesis type:	Master's Thesis / Essay
Language:	English
Date Deposited:	07 Jul 2020 07:48
Last Modified:	07 Jul 2020 07:48
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/22455

Actions (login required)

View Item