Brain Cancer Drug Discovery: Clinical Trials, Drug Classes, Targets, and Combinatorial Therapies.

Jan 31, 2022

Contributor: Aleksandr V Sokolov,Samira A Dostdar,Misty M Attwood,Aleksandra A Krasilnikova,Anastasia A Ilina,Amina Sh Nabieva,Anna A Lisitsyna,Vladimir N Chubarev,Vadim V Tarasov,Helgi B Schiöth

Brain Cancer Drug Discovery: Clinical Trials, Drug Classes, Targets, and Combinatorial Therapies.

Brain cancer is a formidable challenge for drug development, and drugs derived from many cutting-edge technologies are being tested in clinical trials. We manually characterized 981 clinical trials on brain tumors that were registered in ClinicalTrials.gov from 2010 to 2020. We identified 582 unique therapeutic entities targeting 581 unique drug targets and 557 unique treatment combinations involving drugs. We performed the classification of both the drugs and drug targets based on pharmacological and structural classifications. Our analysis demonstrates a large diversity of agents and targets. Currently, we identified 32 different pharmacological directions for therapies that are based on 42 structural classes of agents. Our analysis shows that kinase inhibitors, chemotherapeutic agents, and cancer vaccines are the three most common classes of agents identified in trials. Agents in clinical trials demonstrated uneven distribution in combination approaches; chemotherapy agents, proteasome inhibitors, and immune modulators frequently appeared in combinations, whereas kinase inhibitors, modified immune effector cells did not as was shown by combination networks and descriptive statistics. This analysis provides an extensive overview of the drug discovery field in brain cancer, shifts that have been happening in recent years, and challenges that are likely to come. SIGNIFICANCE STATEMENT: This review provides comprehensive quantitative analysis and discussion of the brain cancer drug discovery field, including classification of drug, targets, and therapies.
Copyright © 2021 by The Author(s).

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About The Expert

Aleksandr V Sokolov

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden (A.V.S., S.A.D., M.M.A., H.B.S.); and Department of Pharmacology, Institute of Pharmacy (A.V.S., S.A.D., A.A.K., A.A.I., A.S.N., A.A.L., V.N.C., V.V.T.) and Institute of Translational Medicine and Biotechnology (V.V.T., H.B.S.), I. M. Sechenov First Moscow State Medical University, Moscow, Russia.

Samira A Dostdar

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden (A.V.S., S.A.D., M.M.A., H.B.S.); and Department of Pharmacology, Institute of Pharmacy (A.V.S., S.A.D., A.A.K., A.A.I., A.S.N., A.A.L., V.N.C., V.V.T.) and Institute of Translational Medicine and Biotechnology (V.V.T., H.B.S.), I. M. Sechenov First Moscow State Medical University, Moscow, Russia.

Misty M Attwood

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden (A.V.S., S.A.D., M.M.A., H.B.S.); and Department of Pharmacology, Institute of Pharmacy (A.V.S., S.A.D., A.A.K., A.A.I., A.S.N., A.A.L., V.N.C., V.V.T.) and Institute of Translational Medicine and Biotechnology (V.V.T., H.B.S.), I. M. Sechenov First Moscow State Medical University, Moscow, Russia.

Aleksandra A Krasilnikova

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden (A.V.S., S.A.D., M.M.A., H.B.S.); and Department of Pharmacology, Institute of Pharmacy (A.V.S., S.A.D., A.A.K., A.A.I., A.S.N., A.A.L., V.N.C., V.V.T.) and Institute of Translational Medicine and Biotechnology (V.V.T., H.B.S.), I. M. Sechenov First Moscow State Medical University, Moscow, Russia.

Anastasia A Ilina

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden (A.V.S., S.A.D., M.M.A., H.B.S.); and Department of Pharmacology, Institute of Pharmacy (A.V.S., S.A.D., A.A.K., A.A.I., A.S.N., A.A.L., V.N.C., V.V.T.) and Institute of Translational Medicine and Biotechnology (V.V.T., H.B.S.), I. M. Sechenov First Moscow State Medical University, Moscow, Russia.

Amina Sh Nabieva

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden (A.V.S., S.A.D., M.M.A., H.B.S.); and Department of Pharmacology, Institute of Pharmacy (A.V.S., S.A.D., A.A.K., A.A.I., A.S.N., A.A.L., V.N.C., V.V.T.) and Institute of Translational Medicine and Biotechnology (V.V.T., H.B.S.), I. M. Sechenov First Moscow State Medical University, Moscow, Russia.

Anna A Lisitsyna

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden (A.V.S., S.A.D., M.M.A., H.B.S.); and Department of Pharmacology, Institute of Pharmacy (A.V.S., S.A.D., A.A.K., A.A.I., A.S.N., A.A.L., V.N.C., V.V.T.) and Institute of Translational Medicine and Biotechnology (V.V.T., H.B.S.), I. M. Sechenov First Moscow State Medical University, Moscow, Russia.

Vladimir N Chubarev

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden (A.V.S., S.A.D., M.M.A., H.B.S.); and Department of Pharmacology, Institute of Pharmacy (A.V.S., S.A.D., A.A.K., A.A.I., A.S.N., A.A.L., V.N.C., V.V.T.) and Institute of Translational Medicine and Biotechnology (V.V.T., H.B.S.), I. M. Sechenov First Moscow State Medical University, Moscow, Russia.

Vadim V Tarasov

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden (A.V.S., S.A.D., M.M.A., H.B.S.); and Department of Pharmacology, Institute of Pharmacy (A.V.S., S.A.D., A.A.K., A.A.I., A.S.N., A.A.L., V.N.C., V.V.T.) and Institute of Translational Medicine and Biotechnology (V.V.T., H.B.S.), I. M. Sechenov First Moscow State Medical University, Moscow, Russia.

Helgi B Schiöth

Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden (A.V.S., S.A.D., M.M.A., H.B.S.); and Department of Pharmacology, Institute of Pharmacy (A.V.S., S.A.D., A.A.K., A.A.I., A.S.N., A.A.L., V.N.C., V.V.T.) and Institute of Translational Medicine and Biotechnology (V.V.T., H.B.S.), I. M. Sechenov First Moscow State Medical University, Moscow, Russia helgis@bmc.uu.se.

References

PubMed