Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation and supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, and gene therapy products) have been approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 of these 1050 drugs were identified as cancer therapeutics or cancer-related drugs, and 120 of them were classified as therapeutic drugs for solid tumors according to their initial indications. These drugs have evolved from small molecules with broad-spectrum antitumor properties in the early stage to monoclonal antibodies (mAbs) and antibody‒drug conjugates (ADCs) with a more precise targeting effect during the most recent decade. These drugs have extended indications for other malignancies, constituting a cancer treatment system for monotherapy or combined therapy. However, the available targets are still mainly limited to receptor tyrosine kinases (RTKs), restricting the development of antitumor drugs. In this review, these 120 drugs are summarized and classified according to the initial indications, characteristics, or functions. Additionally, RTK-targeted therapies and immune checkpoint-based immunotherapies are also discussed. Our analysis of existing challenges and potential opportunities in drug development may advance solid tumor treatment in the future.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13045-022-01362-9.

Related collections

Most cited references 899

Record: found
Abstract: found
Article: not found

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

0 comments Cited 44521 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: found

Is Open Access

Highly accurate protein structure prediction with AlphaFold

John Jumper, Richard Evans, Alexander Pritzel … (2021)

Proteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort 1 – 4 , the structures of around 100,000 unique proteins have been determined 5 , but this represents a small fraction of the billions of known protein sequences 6 , 7 . Structural coverage is bottlenecked by the months to years of painstaking effort required to determine a single protein structure. Accurate computational approaches are needed to address this gap and to enable large-scale structural bioinformatics. Predicting the three-dimensional structure that a protein will adopt based solely on its amino acid sequence—the structure prediction component of the ‘protein folding problem’ 8 —has been an important open research problem for more than 50 years 9 . Despite recent progress 10 – 14 , existing methods fall far short of atomic accuracy, especially when no homologous structure is available. Here we provide the first computational method that can regularly predict protein structures with atomic accuracy even in cases in which no similar structure is known. We validated an entirely redesigned version of our neural network-based model, AlphaFold, in the challenging 14th Critical Assessment of protein Structure Prediction (CASP14) 15 , demonstrating accuracy competitive with experimental structures in a majority of cases and greatly outperforming other methods. Underpinning the latest version of AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm. AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

0 comments Cited 14155 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

Martin Jinek, Krzysztof Chylinski, Ines Fonfara … (2012)

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.

0 comments Cited 3728 times – based on 0 reviews      Review now

All references

Author and article information

Contributors

Qing Wu:

ORCID: https://orcid.org/0000-0002-1442-0183

wq0826@hmc.edu.cn

Wei Qian: 2514010@zju.edu.cn

Xiaoli Sun: sxlyzh@zju.edu.cn

Shaojie Jiang:

ORCID: https://orcid.org/0000-0001-9996-7016

jsj1983@hmc.edu.cn

Journal

Journal ID (nlm-ta): J Hematol Oncol

Journal ID (iso-abbrev): J Hematol Oncol

Title: Journal of Hematology & Oncology

Publisher: BioMed Central (London )

ISSN (Electronic): 1756-8722

Publication date (Electronic): 8 October 2022

Publication date PMC-release: 8 October 2022

Publication date Collection: 2022

Volume: 15

Electronic Location Identifier: 143

Affiliations

[1 ]GRID grid.506977.a, ISNI 0000 0004 1757 7957, School of Medical Imaging, , Hangzhou Medical College, ; Hangzhou, 310053 Zhejiang China

[2 ]GRID grid.412465.0, Department of Radiology, School of Medicine, , The Second Affiliated Hospital, Zhejiang University, ; Hangzhou, 310009 Zhejiang China

[3 ]GRID grid.452661.2, ISNI 0000 0004 1803 6319, Department of Radiation Oncology, School of Medicine, , The First Affiliated Hospital, Zhejiang University, ; Hangzhou, 310003 Zhejiang China

Author information

Qing Wu https://orcid.org/0000-0002-1442-0183

Shaojie Jiang https://orcid.org/0000-0001-9996-7016

Article

Publisher ID: 1362

DOI: 10.1186/s13045-022-01362-9

PMC ID: 9548212

PubMed ID: 36209184

SO-VID: 3da71788-4bae-4b05-ae88-75261c2dafcb

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 26 July 2022

Date accepted : 2 October 2022

Funding

Funded by: Basic Research Project of Hangzhou Medical College

Award ID: KYQN202007

Award Recipient : Qing Wu

Funded by: Zhejiang Provincial Natural Science Foundation of China

Award ID: LY21C070002

Award Recipient : Shaojie Jiang

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: the united states food and drug administration,solid tumors,receptor tyrosine kinase inhibitors,immune checkpoint blockades

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: the united states food and drug administration, solid tumors, receptor tyrosine kinase inhibitors, immune checkpoint blockades

Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021

Read this article at

Abstract

Supplementary Information

Related collections

Karger: Oncology

Most cited references 899

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Highly accurate protein structure prediction with AlphaFold

A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 81

Cited by 82

Most referenced authors 18,114