Combination of the First-in-Class Imipridone ONC201 and Standard Anticancer Therapies as a Rational Approach for
Brahmi Shenoy1, Miloni Mandani1, Meena Chintamaneni2
1Department of Biological Sciences, Sunandan Divatia of School of Science, SVKM's NMIMS (Deemed-to-Be) University, V.L. Mehta Road, Vile Parle (W), Mumbai 400056, India.
Abstract:
The development of drugs for cancer treatment faces critical challenges due to the heterogeneity in cancers, metastatic nature of the disease, lack of efficacy, toxicity, and drug resistance. This makes it quite important to understand the complexities of cancer as well as the limitations of druggable targets. ONC201 (also known as dordaviprone/TIC10/ModeysoTM), a first-in-class member of the imipridone family, has been shown to kill cancer cells selectively. Recently, it has received FDA approval as the first and only treatment for recurrent H3K27M-mutant diffuse midline glioma. The unique pharmacophore, favorable therapeutic index, ability to induce TRAIL and the integrated stress response (ISR), activation of natural killer cells, and ability to diffuse across the blood-brain barrier are the unique characteristics of ONC201. ONC201 has shown effectiveness against various cancers, and this has been evident in many preclinical studies. ONC201 as a single agent, although useful, has some limitations, which could be addressed by using combination strategies. ONC201 has shown synergism with other drugs, leading to greater tumor cell death or reduced tumor growth. Next-generation imipridones, viz. ONC206 and ONC212, are more potent analogs of ONC201 and exhibit similar characteristics. In this review, we discuss the therapeutic potential of ONC201 and its analogs using combination strategies across different cancers.
Insights
ONC201, a novel cancer drug, shows promise in treating various cancers, especially when combined with other therapies. Its analogs, ONC206 and ONC212, offer enhanced potency for improved cancer treatment strategies.
Area of Science:
- Oncology
- Pharmacology
- Drug Development
Background:
- Cancer drug development faces challenges like heterogeneity, metastasis, resistance, and toxicity.
- ONC201, a first-in-class imipridone, selectively kills cancer cells and is FDA-approved for H3K27M-mutant glioma.
- Key features of ONC201 include its unique pharmacophore, safety profile, ability to induce TRAIL and ISR, NK cell activation, and blood-brain barrier penetration.
Purpose of the Study:
- To review the therapeutic potential of ONC201 and its analogs.
- To explore combination strategies for enhancing cancer treatment efficacy.
- To discuss the application of ONC201 and its analogs across various cancer types.
Main Methods:
- Literature review of preclinical and clinical studies on ONC201 and its analogs.
- Analysis of combination strategies involving ONC201.
- Evaluation of the efficacy and mechanisms of action of imipridones in different cancers.
Main Results:
- ONC201 demonstrates effectiveness as a single agent and in combination therapies across various cancers.
- Combination strategies with ONC201 show synergistic effects, leading to enhanced tumor cell death and reduced tumor growth.
- Next-generation imipridones (ONC206, ONC212) are more potent analogs with similar therapeutic characteristics.
Conclusions:
- ONC201 and its analogs hold significant therapeutic potential for diverse cancers.
- Combination strategies are crucial for overcoming limitations and maximizing the efficacy of ONC201.
- Further research into imipridone-based combination therapies could lead to novel and effective cancer treatments.
More Related Videos
08:57Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
Published on: October 5, 2017
06:15Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:27Tumor Immunotherapy
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:56Treatment Resistant Cancers
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...