Full Answer
Are small molecule inhibitors targeted?
Figure 1: Summarized known small molecule inhibitors as targeted therapy. Schematic representation of pathways that are usually aberrantly activated in cancer, along with the small molecule inhibitors of critical cancer targets List of small ...
What is the history of small-molecule targeted cancer drugs?
Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies.
Can the combination of inhibitors help treat cancer?
Single-use of small molecule inhibitors to treat cancer often has mutation sites that affect drug treatment. Although few inhibitor combinations are approved by FDA, the combination of inhibitors can solve this problem.
What are small molecule inhibitors targeting the apoptosis of cancer cells?
Small molecule inhibitors targeting the apoptosis. Small molecule drugs that potentially restore the wild type tumor suppressor functions to the mutated p53 have been developed. CP-31398, Phikan083, the tenovins, MI-219 and the nutlins are some of the small molecules that target the mutated p53 and induce apoptosis of cancer cells [53-57].
Why are selective inhibitors used in cancer?
Selective inhibitors can also be used as chemical probes to explore the epigenetic effects and biological processes induced by HD ACs in cancer cells. Additionally, HDAC inhibitors are used in combination with other antitumor drugs to optimize their efficacy and conquer drug toxicity and resistance.
When was the first tyrosine kinase inhibitor imatinib approved?
Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies.
What are the targets of the NMPA?
The targets of these drugs cover a large scope including kinases, epigenetic regulatory proteins, DNA damage repair enzymes, and proteasomes.
How many kinase inhibitors are approved in the US?
We in the above summarize the anti-cancer kinase inhibitors approved by the US FDA and NMPA of China. To date, a total of 70 kinase inhibitors have been approved to use in the clinic, which accounts for almost 80% of all approved small-molecule targeted anti-cancer drugs (89 in total).
What is targeted cancer treatment?
Over the past two decades, there has been a tremendous shift in cancer treatment, from broad-spectrum cytotoxic drugs to targeted drugs. 1 Compared with traditional chemotherapy drugs, targeted drugs can specifically target cancer cells but spare normal cells, hence having high potency and low toxicity.
How many small molecule antitumor drugs will be approved by the FDA in 2020?
By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance.
What is the best treatment for cancer?
Drug treatment together with surgical operation, radiotherapy and biotherapy constitute the main approaches to cancer treatment. For a long time, chemotherapy , which is a method of killing tumor cells and/or inhibiting the growth and proliferation of tumor cells by chemical drugs, was the only approach to cancer drug therapy. The biggest characteristic of chemotherapy is the inability to distinguish between cancer cells and normal cells, resulting in significant toxicity and side effects. Over the past two decades, there has been a tremendous shift in cancer treatment, from broad-spectrum cytotoxic drugs to targeted drugs. 1 Compared with traditional chemotherapy drugs, targeted drugs can specifically target cancer cells but spare normal cells, hence having high potency and low toxicity. Encouraged by the approval of the first small-molecule tyrosine kinase inhibitor (TKI) imatinib for clinical use by the US Food and Drug Administration (FDA) in 2001, 2 targeted drugs have rapidly developed and entered a golden period of development. In the past 20 years, there has been a significant increase in FDA-approved targeted drugs for cancer treatment.
Abstract
Research on molecular targeted therapy of tumors is booming, and novel targeted therapy drugs are constantly emerging. Small molecule targeted compounds, novel targeted therapy drugs, can be administered orally as tablets among other methods, and do not draw upon genes, causing no immune response.
Introduction
The tumor is a neoplastic proliferation of the abnormal cells of the body formed. Usually, it is abnormal tissue mass on parts of the body. It refers to a new organism generated by abnormal proliferation and the differentiating process of body cells based on a range of initiating and promoting elements.
Classification of Small Molecule Targeted Compounds
The principle of small molecule targeted compounds is to target the molecular biology basis of tumorigenesis, usually to regulate the activity of protein targets. Depending on the type of target, small molecule targeted compounds play different roles.
The Application of Small Molecule Targeted Compounds in Cancers
In this review, we classify the existing small molecule targeted compounds for the carcinoma therapeutic process into the following four categories according to the different channels targeted. We have screened out 103 small molecule targeted compounds for cancer treatment from the drugs approved by the FDA.
Mechanism of Resistance of Small Molecule Inhibitors
Drug resistance is a common phenomenon in the treatment of cancer, which is divided into acquired resistance and natural resistance. In cancer chemotherapy, many cancer patients begin to be sensitive to chemotherapeutic drugs.
The Combined Therapy of Small Molecule Targeted Compounds
The purpose of combination therapy is to overcome and reverse the drug resistance of inhibitors, reduce side effects and achieve better therapeutic results through the combination of multiple pathway inhibitors. Single-use of small molecule inhibitors to treat cancer often has mutation sites that affect drug treatment.
Conclusion and Perspectives
Small molecule targeted compounds have been developed in clinical medicine for decades, prolonging the survival time of cases subjected to advanced or refractory tumors. However, there are still insufficient approved drugs for practical use for several reasons.
How many antitumor drugs will be available in 2021?
By the end of June 2021, worldwide 96 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China, which majorly includes 73 kinase Inhibitors, beside other including Epigenetic Inhibitors, inhibitors of BCL-2, hedgehog pathway, proteasome, and PARP.
When was the first tyrosine kinase inhibitor approved?
First cancer targeting tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, since then an increasing number of small-molecule targeted drugs have been developed and approved for the treatment of cancer. By the end of June 2021, worldwide 96 ...
What is pyrotinib used for?
Pyrotinib is an irreversible dual pan-ErbB receptor tyrosine kinase inhibitor approved in China for use in combination with capecitabine for the treatment of HER2-positive, advanced or metastatic breast cancer in patients previously treated with anthracycline or taxane chemotherapy. 43. Braftovi. Encorafenib.
What is the exon 19 deletion of Pfizer?
Pfizer. 2018. In Oct 2018, the FDA approved Dacomitin ib for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test.
When was Sotorasib approved?
Sotorasib. KRAS G12C. Amgen. 2021. On May 28, 2021, the FDA approved Sotorasib for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.
Is Abemaciclib a monotherapy?
On Sep 2017, the FDA approved abemaciclib in combination with fulvestrant or as monotherapy for women with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. 40. Fotivda.
Is Ibrutinib approved for SLL?
Ibrutinib was approved by the FDA for the treatment of Mantle Cell Lymphoma, and later in February 2014 for the treatment of Chronic Lymphocytic Leukemia. Later approved for Waldenström's macroglobulinemia (2015), Small lymphocytic lymphoma (SLL) (2016) with or without 17p deletion and mantle cell lymphoma (2017) 23.
What is a cancer growth blocker?
A cancer growth blocker is a targeted drug that blocks the growth factors that trigger cancer cells to divide and grow. Scientists are looking at different ways of doing this such as: lowering levels of the growth factor in the body. blocking the growth factor receptor on the cancer cell.
What is the drug that blocks proteasomes from working?
The cell can then use them to make new proteins that it does need. Drug treatments that block proteasomes from working are called proteasome inhibitors. They cause a build up of unwanted proteins in the cell, which makes the cancer cells die.
What is a tyrosine kinase inhibitor?
Tyrosine kinase inhibitors (TKIs) block chemical messengers (enzymes) called tyrosine kinases. Tyrosine kinases help to send growth signals in cells, so blocking them stops the cell growing and dividing. Cancer growth blockers can block one type of tyrosine kinase or more than one type.
What is the BRAF inhibitor?
BRAF inhibitors directly block a protein called BRAF. BRAF is a chemical messenger (enzyme) that controls how cells grow and send signals. Some cancers have a change (mutation) in the BRAF gene. This genetic change makes the cancer cells produce too much BRAF protein, which can make cancer cells grow.
What is the name of the enzyme that blocks the action of a group of enzymes that remove chemicals called ace
Histone deacetylase inhibitors are also called HDAC inhibitors or HDIs. They block the action of a group of enzymes that remove chemicals called acetyl groups from particular proteins. This can stop the cancer cell from using some genes that would help it to grow and divide. This might kill the cancer cell completely.
Why is it not easy to group targeted therapies into different types?
It isn't easy to group targeted therapies into different types because the groups often overlap. This can be confusing. For example, some cancer growth blockers stop the growth of blood vessels to the growing cancer. So they are also working as an anti angiogenic drugs.
What is the function of fibroblast growth factor?
fibroblast growth factor (FGF) – controls cell growth. Each growth factor works by attaching to the corresponding receptor on the cell surface. For example, EGF binds to epidermal growth factor receptor (EGFR). Tyrosine Kinases are chemical messengers (enzymes) used by cells to control how they grow and divide.
Small Molecule Proteosome Inhibitors
- It is intriguing to note that pathways that help to maintain cellular homeostasis in normal cells are those that favour cancer cell survival by up regulating cell proliferation and inhibiting apoptosis of tumor cells. The ubiquitin proteosome pathway (UPP) is one such pathway that involves degrad…
Small Molecule Mmps and Hsps Inhibitors
- Matrix metalloproteinases (MMPs) are a group of endopeptidases that degrade the extracellular matrix (ECM), thus paving the way for cell migration and invasion . More than 20 MMPs have been identified in humans, the activities of which are regulated in vivo by the tissue inducers of metalloproteinases (TIMPs). The gelatinases MMP-2 and MMP-9 have been found to target man…
Small Molecule Inhibitors Targeting The Apoptosis
- Small molecule drugs that potentially restore the wild type tumor suppressor functions to the mutated p53 have been developed. CP-31398, Phikan083, the tenovins, MI-219 and the nutlins are some of the small molecules that target the mutated p53 and induce apoptosis of cancer cells [53-57]. Another class of small molecule drugs are the caspase activators that induce apoptosi…
Introduction
- The traditional means of cancer management are chemotherapy, radiation therapy and surgery. Chemotherapy that involves the use of a single drug at a time (single-agent chemotherapy) or several drugs (combination therapy) usually target killing of rapidly dividing cancer cells. To overcome the drawbacks of traditional cancer therapies, the approach has been to search for sp…
Small Molecule Inhibitors
- Small molecule cancer drugs, because of their small size, have been successfully used to target the extracellular, cell surface ligand-binding receptors as well as the intracellular proteins, including anti-apoptotic proteins that play a key role in transducing downstream signalling for cell growth and metastasis promotion. Most of these drugs inhi...
List of Small Molecule Inhibitors For Cancer Therapy
- Many cancer therapeutic drugs have been approved for use and several more are being studied in clinical trials.
Limitation of The Use of Small Molecules
- More than 20 small molecule drugs have been approved for clinical use and are being successfully used in cancer treatment. Still, there are certain limitations that are to be considered and overcome while designing more active drugs so as to reduce the failure rates of the drugs at the clinical level. Certain small molecule inhibitors bind to multiple molecular targets including c…
Conclusions
- Over the last few decades, the success of small molecule cancer drugs over conventional chemotherapy has been clearly demonstrated. Majority of the inhibitors that have been developed and currently in clinical use target the kinases, which include the receptor molecules as well as downstream regulators . Labclinics includes in its catalog, the catalog from ApexBio, a leading p…