Adavosertib - Cancer Science

What is Adavosertib?

Adavosertib, also known as AZD1775, is an experimental anticancer drug. It is an inhibitor of the Wee1 kinase, an enzyme that plays a critical role in the regulation of the cell cycle. By inhibiting Wee1 kinase, adavosertib disrupts the cell cycle, leading to cell death, particularly in cancer cells with DNA damage or defective DNA repair mechanisms.

How Does Adavosertib Work?

Adavosertib targets the Wee1 G2 checkpoint in the cell cycle. Wee1 kinase normally inhibits the transition from the G2 phase to the M phase (mitosis), allowing time for DNA repair. Inhibition of Wee1 by adavosertib forces cells with damaged DNA to prematurely enter mitosis, leading to mitotic catastrophe and cell death. This mechanism is particularly effective in cancer cells, which often harbor extensive DNA damage.

What Types of Cancer is Adavosertib Being Tested For?

Adavosertib is being investigated for use in a variety of cancers, including ovarian cancer, pancreatic cancer, colorectal cancer, and small cell lung cancer. Its efficacy is often evaluated in combination with other therapies, such as chemotherapy or radiation therapy.

What are the Potential Benefits of Adavosertib?

The primary benefit of adavosertib is its ability to selectively target cancer cells with defective DNA repair mechanisms. This selectivity can potentially lead to more effective treatments with fewer side effects compared to traditional therapies. Furthermore, adavosertib can enhance the efficacy of existing treatments by sensitizing cancer cells to DNA-damaging agents.

What are the Side Effects of Adavosertib?

Like many anticancer drugs, adavosertib is associated with a range of side effects. Common side effects include nausea, vomiting, diarrhea, and fatigue. More severe effects can include hematologic toxicities like neutropenia and thrombocytopenia. Patients undergoing treatment with adavosertib require careful monitoring to manage these side effects.

What is the Current Status of Clinical Trials?

Adavosertib is currently undergoing clinical trials to evaluate its safety and efficacy. Several phase I and II trials have shown promising results, particularly in combination with other therapies. Ongoing research aims to better understand the optimal usage of adavosertib, its efficacy across different cancer types, and how to mitigate its side effects.

What are the Future Directions for Adavosertib Research?

Future research on adavosertib will likely focus on identifying biomarkers to predict which patients will benefit most from treatment. Additionally, researchers are exploring the combination of adavosertib with novel therapies, such as immune checkpoint inhibitors and other targeted agents. Understanding the molecular mechanisms underlying resistance to adavosertib is also a key area of investigation.

Relevant Publications

Disulfiram/copper complex improves the effectiveness of the WEE1 inhibitor Adavosertib in p53 deficient non-small cell lung cancer via ferroptosis.

Issue Release: 2024

Adavosertib-encapsulated metal-organic frameworks for p53-mutated gallbladder cancer treatment via synthetic lethality.

Issue Release: 2024

Identification of m6A-associated autophagy genes in non-alcoholic fatty liver.

Issue Release: 2024

Population Pharmacokinetic Modeling of Adavosertib (AZD1775) in Patients with Solid Tumors.

Issue Release: 2024

WEE1 Inhibitor Adavosertib Exerts Antitumor Effects on Colorectal Cancer, Especially in Cases with Mutations.

Issue Release: 2024

Safety, tolerability, pharmacokinetics, and antitumor activity of adavosertib in Japanese patients with advanced solid tumors: A phase I, open-label study.

Issue Release: 2024

Exploiting WEE1 kinase activity as FUS::DDIT3-dependent therapeutic vulnerability in myxoid liposarcoma.

Issue Release: 2024

A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170).

Issue Release: 2024

WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation.

Issue Release: 2024

Novel Combinations of Immunotherapies or DNA Damage Repair Inhibitors in Platinum-Refractory Extensive-Stage Small-Cell Lung Cancer: The Phase II BALTIC Study.

Issue Release: 2024

Genome-scale clustered regularly interspaced short palindromic repeats screen identifies nucleotide metabolism as an actionable therapeutic vulnerability in diffuse large B-cell lymphoma.

Issue Release: 2024

Evolving treatment paradigms for platinum-resistant ovarian cancer: An update narrative review.

Issue Release: 2024

Adavosertib and Beyond: Biomarkers, Drug Combination and Toxicity of WEE1 Inhibitors.

Issue Release: 2023

Synergistic effect of adavosertib and fimepinostat on acute myeloid leukemia cells by enhancing the induction of DNA damage.

Issue Release: 2023

A phase Ib study of adavosertib, a selective Wee1 inhibitor, in patients with locally advanced or metastatic solid tumors.

Issue Release: 2023

Combined PARP and WEE1 inhibition triggers anti-tumor immune response in BRCA1/2 wildtype triple-negative breast cancer.

Issue Release: 2023

A Phase Ib Study Assessing the Safety, Tolerability, and Efficacy of the First-in-Class Wee1 Inhibitor Adavosertib (AZD1775) as Monotherapy in Patients with Advanced Solid Tumors.

Issue Release: 2023

Phase 1 study of belinostat and adavosertib in patients with relapsed or refractory myeloid malignancies.

Issue Release: 2023

Targeting WEE1 kinase as a p53-independent therapeutic strategy in high-risk and relapsed acute lymphoblastic leukemia.

Issue Release: 2023

Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth.

Issue Release: 2023

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