scholarly journals Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lei Zhong ◽  
Yueshan Li ◽  
Liang Xiong ◽  
Wenjing Wang ◽  
Ming Wu ◽  
...  
Keyword(s):  
Small Molecule ◽  
Kinase Inhibitor ◽  
Cancer Drugs ◽  
Drug Candidates ◽  
Chemotherapy Drugs ◽  
National Medical ◽  
Anti Cancer ◽  
The Us ◽  
Us Fda ◽  
Approved Drugs

AbstractDue to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. 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. 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. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.

scholarly journals Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond

2019 ◽  
Vol 40 (6) ◽  
pp. 1573-1604 ◽  
Author(s):  
Maria E Cabanillas ◽  
Mabel Ryder ◽  
Camilo Jimenez
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Rapid Evolution ◽  
Anaplastic Thyroid Cancer ◽  
The Us ◽  
Advanced Thyroid Cancer ◽  
Inhibitor Drug ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract The treatment of advanced thyroid cancer has undergone rapid evolution in the last decade, with multiple kinase inhibitor drug approvals for each subtype of thyroid cancer and a number of other commercially available drugs that have been studied for this indication. Although most of the US Food and Drug Administration (FDA)–approved drugs are antiangiogenic multikinase inhibitors—vandetanib, cabozantinib, sorafenib, lenvatinib—there are two FDA indications that are mutation specific—dabrafenib/trametinib for BRAF-mutated anaplastic thyroid cancer and larotrectinib for NTRK-fusion thyroid cancer. Furthermore, other mutation-specific drugs, immunotherapies, and novel strategies for advanced thyroid cancer are under investigation. Understanding the molecular basis of thyroid cancer, the drugs of interest for treatment of advanced thyroid cancer, and how these drugs can be administered safely and in the appropriate clinical scenario are the topics of this review.

scholarly journals In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Shao-Xing Dai ◽  
Wen-Xing Li ◽  
Fei-Fei Han ◽  
Yi-Cheng Guo ◽  
Jun-Juan Zheng ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Supportive Role ◽  
Starting Point ◽  
Anti Cancer ◽  
Approved Drugs ◽  
Alternative Resource

Abstract There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed that 75% of the 5278 compounds are highly similar to the approved anti-cancer drugs. Based on the predicted anti-cancer compounds, we identified 57 anti-cancer plants by activity enrichment. The identified plants are widely distributed in 46 genera and 28 families, which broadens the scope of the anti-cancer drug screening. Finally, we constructed a network of predicted anti-cancer plants and approved drugs based on the above results. The network highlighted the supportive role of the predicted plant in the development of anti-cancer drug and suggested different molecular anti-cancer mechanisms of the plants. Our study suggests that the predicted compounds and plants from TCM database offer an attractive starting point and a broader scope to mine for potential anti-cancer agents.

Real-world treatment patterns, health care resource utilization (HRU), and costs among patients with Waldenstrom macroglobulinemia (WM) initiating therapy.

2016 ◽  
Vol 34 (7_suppl) ◽  
pp. 17-17
Author(s):  
Brad Schenkel ◽  
Lorie Ellis ◽  
Stephanie Korrer ◽  
Stacey DaCosta Byfield
Keyword(s):  
Index Date ◽  
B Cell Lymphoma ◽  
Drug Regimen ◽  
Current Therapy ◽  
Anti Cancer ◽  
The Us ◽  
Us Fda ◽  
Line Of Therapy ◽  
Initial Drug

17 Background: WM is a rare, indolent B-cell lymphoma with 1000 to 1500 new cases diagnosed annually in the US. The disease is incurable with current therapy. Prior to January 2015 when ibrutinib was approved by the US FDA for WM, there were no therapies approved in this indication. This study describes initial systemic anti-cancer therapy (SACT) and HRU among WM patients (pts). Methods: A retrospective study using a large, national US claims database from 1/2007-10/2013 was conducted. Adult WM pts ( ≥ 2 claims for WM) with ≥ 1 claim for SACT were identified; the first SACT claim date was the index date. Pts were required to have a WM diagnosis within 3 months (m) prior to the index date and be continuously enrolled (CE) in the health plan for 12m pre- and ≥ 6m post-index date. Pregnant pts and those with SACT in the pre-index period were excluded. The first line of therapy (LOT1) period was examined; the LOT started at index date and the regimen included all drugs received within 60 days. The LOT ended at the earliest of, start of a new drug, ≥ 60-day gap in receipt of initial drug regimen, death or CE end. All-cause HRU and costs during LOT1 were examined. Results: There were 161 WM pts identified. 66% of pts were ≥ 65 yrs (mean age 69), 55% were male, and by insurance type, 49% were Medicare Advantage pts vs. 51% commercially insured. Mean total follow-up time was 23m, and mean duration of LOT1 was 4.7m. The top 4 most common LOT1 regimens accounted for 71% of patients: Rituximab (R) only (39%); bortezomib+ R (14%); bendamustine+ R (9%) and cyclophosphamide+ R (9%). No other regimens identified accounted for more than 4% of pts. Overall, 96% and 81% of pts had ≥ 1 office or hospital outpatient visit with mean per patient per month (PPPM) visits of 3.55 (standard deviation, SD = 2.41) and 2.60 (SD = 3.06), respectively. Approximately 25% and 21% had ≥ 1 ER visit or inpatient stay with mean PPPM visits of 0.11 (SD = 0.24) and 0.06 (SD = 0.16), respectively. Total mean PPPM healthcare costs during LOT1 was $13,589 (SD = $13,404). Conclusions: HRU and costs were high among WM pts initiating SACT. Future studies should examine whether differences in LOT1 regimen choice are associated with differences in cost and outcomes.

Japan’s conditional early approval program for innovative cancer drugs: Comparison of the regulatory processes with the US FDA and the EMA

Cancer Cell ◽  
2021 ◽  
Author(s):  
Anju Murayama ◽  
Munetaka Ueda ◽  
Sunil Shrestha ◽  
Tetsuya Tanimoto ◽  
Akihiko Ozaki
Keyword(s):  
Cancer Drugs ◽  
Regulatory Processes ◽  
The Us ◽  
Us Fda

Mo1929 Small-Molecule Parkinson's Disease Kinase Inhibitor LRRK2-in-1 Demonstrates Potent Anti-Cancer Activity Through Inhibition of DCLK1

2014 ◽  
Vol 146 (5) ◽  
pp. S-694
Author(s):  
Nathaniel Weygant ◽  
Dongfeng Qu ◽  
William L. Berry ◽  
Randal May ◽  
Parthasarathy Chandrakesan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Small Molecule ◽  
Kinase Inhibitor ◽  
Anti Cancer ◽  
Cancer Activity

Screening of 129 FDA approved anti-cancer drugs in colorectal cancer cell lines resistant to oxaliplatin or irinotecan (SN38).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 642-642 ◽  
Author(s):  
Jan Stenvang ◽  
Christine Hjorth Andreassen ◽  
Nils Brünner
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cell Viability ◽  
Cell Line ◽  
Cell Lines ◽  
Resistant Cell ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Drug Candidates ◽  
Anti Cancer

642 Background: In metastatic colorectal cancer (mCRC) only 3 cytotoxic drugs (oxaliplatin, irinotecan and fluorouracil (5-FU)) are approved and the first and second line response rates are about 50% and 10-15%, respectively. Thus, new treatment options are needed. Novel anti-cancer drug candidates are primarily tested in an environment of drug resistance and the majority of novel drug candidates fail during clinical development. Therefore, “repurposing” of drugs has emerged as a promising strategy to apply established drugs in novel indications. The aim of this project was to screen established anti-cancer drugs to identify candidates for testing in mCRC patients relapsing on standard therapy. Methods: We applied 3 parental (drug sensitive) CRC cell lines (HCT116, HT29 and LoVo) and for each cell line also an oxaliplatin and irinotecan (SN38) resistant cell line. We obtained 129 FDA approved anti-cancer drugs from the Developmental Therapeutics Program (DTP) at the National Cancer Institute (NCI) ( https://dtp.cancer.gov/ ). The parental HT29 cell line and the drug resistant sublines HT29-SN38 and HT29-OXPT were exposed to 3 concentrations of each of the anti-cancer drugs. The effect on cell viability was analyzed by MTT assays. Nine of the drugs were analyzed for effect in the LoVo and HCT116 and the SN38- and oxaliplatin-resistant derived cell lines. Results: None of the drugs caused evident differential response between the resistant and sensitive cells or between the SN38 and oxaliplatin resistant cells. The screening confirmed the resistance as the cells displayed resistance to drugs in the same class as the one they were made resistant to. Of the drugs, 45 decreased cell viability in the HT29 parental and oxaliplatin- or SN-38 resistant cell lines. Nine drugs were tested in all nine CRC cell lines and eight decrease cell viability in the nine cell lines. These included drugs in different classes such as epigenetic drugs, antibiotics, mitotic inhibitors and targeted therapies. Conclusions: This study revealed several possible new “repurposing” drugs for CRC therapy, by showing that 45 FDA-approved anti-cancer drugs decrease cell viability in CRC cell lines with acquired drug resistance.

scholarly journals Drug Repurposing Approaches to Combating Viral Infections

2020 ◽  
Vol 9 (11) ◽  
pp. 3777
Author(s):  
Jay Trivedi ◽  
Mahesh Mohan ◽  
Siddappa N. Byrareddy
Keyword(s):  
Viral Infections ◽  
Drug Repurposing ◽  
Therapeutic Drug ◽  
Novel Drugs ◽  
Anti Cancer ◽  
Immunodeficiency Virus ◽  
The Us ◽  
Us Fda ◽  
Cancer Agent ◽  
The 1960S

Development of novel antiviral molecules from the beginning costs an average of $350 million to $2 billion per drug, and the journey from the laboratory to the clinic takes about 10–15 years. Utilization of drug repurposing approaches has generated substantial interest in order to overcome these drawbacks. A drastic reduction in the failure rate, which otherwise is ~92%, is achieved with the drug repurposing approach. The recent exploration of the drug repurposing approach to combat the COVID-19 pandemic has further validated the fact that it is more beneficial to reinvestigate the in-practice drugs for a new application instead of designing novel drugs. The first successful example of drug repurposing is zidovudine (AZT), which was developed as an anti-cancer agent in the 1960s and was later approved by the US FDA as an anti-HIV therapeutic drug in the late 1980s after fast track clinical trials. Since that time, the drug repurposing approach has been successfully utilized to develop effective therapeutic strategies against a plethora of diseases. Hence, an extensive application of the drug repurposing approach will not only help to fight the current pandemics more efficiently but also predict and prepare for newly emerging viral infections. In this review, we discuss in detail the drug repurposing approach and its advancements related to viral infections such as Human Immunodeficiency Virus (HIV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

scholarly journals Fatal toxicity of chloroquine or hydroxychloroquine with metformin in mice

2020 ◽  
Author(s):  
N.V Rajeshkumar ◽  
Shinichi Yabuuchi ◽  
Shweta G. Pai ◽  
Anirban Maitra ◽  
Manuel Hidalgo ◽  
...  
Keyword(s):  
Adverse Drug Reactions ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
Cancer Drugs ◽  
Drug Reactions ◽  
Cautionary Note ◽  
Clinical Toxicity ◽  
Do No Harm ◽  
Anti Cancer ◽  
The Us

AbstractGuided by the principle of primum non nocere (first do no harm), we report a cautionary note on the potential fatal toxicity of chloroquine (CQ) or hydroxychloroquine (HCQ) in combination with anti-diabetic drug metformin. We observed that the combination of CQ or HCQ and metformin, which were used in our studies as potential anti-cancer drugs, killed 30-40% of mice. While our observations in mice may not translate to toxicity in humans, the reports that CQ or HCQ has anti-COVID-19 activity, the use of CQ resulting in toxicity and at least one death, and the recent Emergency Use Authorization (EUA) for CQ and HCQ by the US Food and Drug Administration (FDA) prompted our report. Here we report the lethality of CQ or HCQ in combination with metformin as a warning of its potential serious clinical toxicity. We hope that our report will be helpful to stimulate pharmacovigilance and monitoring of adverse drug reactions with the use of CQ or HCQ, particularly in combination with metformin.

Novel Small Molecule IL-6 Inhibitors as Anti-Cancer Drugs

2001 ◽  
pp. 429-434
Author(s):  
Bernd Stein ◽  
May Sutherland ◽  
Stephanie Lipps ◽  
Joseph Lewcock ◽  
Helen Brady ◽  
...  
Keyword(s):  
Small Molecule ◽  
Cancer Drugs ◽  
Anti Cancer
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