The Renaissance of Cyclin Dependent Kinase Inhibitors

SIMPLE SUMMARY: This review provides an overview of the state of knowledge and general understanding of CDK inhibitors currently under development or clinically approved, with a particular focus on the treatment of head and neck cancer. Especially in combination therapy, cyclin-dependent kinase inhibitors exhibit a synergistic effect by attenuating chemo-, radio-, or immune-resistance in some tumor entities, thus improving the success of cancer therapy. ABSTRACT: Cyclin-dependent kinases (CDK) regulate cell cycle progression. During tumor development, altered expression and availability of CDKs strongly contribute to impaired cell proliferation, a hallmark of cancer. In recent years, targeted inhibition of CDKs has shown considerable therapeutic benefit in a variety of tumor entities. Their success is reflected in clinical approvals of specific CDK4/6 inhibitors for breast cancer. This review provides a detailed insight into the molecular mechanisms of CDKs as well as a general overview of CDK inhibition. It also summarizes the latest research approaches and current advances in the treatment of head and neck cancer with CDK inhibitors. Instead of monotherapies, combination therapies with CDK inhibitors may especially provide promising results in tumor therapy. Indeed, recent studies have shown a synergistic effect of CDK inhibition together with chemo- and radio- and immunotherapy in cancer treatment to overcome tumor evasion, which may lead to a renaissance of CDK inhibitors.