Expert opinion on drug discovery
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Expert Opin Drug Discov · Jan 2017
ReviewThe need for fundamental reforms in the pain research field to develop innovative drugs.
Chronic pain is a major healthcare issue owing to its high prevalence, significant physical and emotional burden on the patients, and huge financial burden on the society. The efficacy of currently available medications is unsatisfactory owing to their limited effect size and the low responder rate (less than 50%). Thus, there is a large unmet need for innovative therapies for chronic pain. ⋯ It has, however, made insufficient progress with respect to the launch of innovative analgesic drugs, because the translation from preclinical to clinical stages has not been satisfactory. Thus, the strategies for developing innovative analgesic drugs are discussed. Expert opinion: Points to be considered in the discovery of drugs for pain relief include: (1) the exclusion of bias incorporation and the alignment of clinical and preclinical endpoints in the assessment of analgesic efficacy; (2) the understanding of primary unmet needs; (3) the assessment of new therapies by biomarker-prioritized frameworks, and (4) the stratification of chronic pain sufferers.
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Expert Opin Drug Discov · Nov 2016
ReviewThe discovery and the development of bendamustine for the treatment of non-Hodgkin lymphoma.
Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid malignancies. The treatment strategy for patients with NHL had remained unchanged until the advent of the era of molecular targeting agents. Although rituximab-containing chemotherapy has improved the response rates and survival of patients with B-cell NHL (B-NHL), several subtypes of B-NHL, especially indolent B-NHL and mantle cell lymphoma (MCL), remain incurable. ⋯ Expert opinion: Bendamustine monotherapy or the use of bendamustine in combination with rituximab is highly effective against various types of hematological malignancies, especially relapsed or refractory indolent B-NHL, and exhibits an acceptable toxicity profile. Furthermore, bendamustine plus rituximab might be a promising treatment option for patients with untreated indolent B-NHL. Therefore, bendamustine has the potential to play an important role in the treatment of malignant lymphoma.
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Expert Opin Drug Discov · Jan 2016
ReviewOpen Access Could Transform Drug Discovery: A Case Study of JQ1.
The cost to develop a new drug from target discovery to market is a staggering $1.8 billion, largely due to the very high attrition rate of drug candidates and the lengthy transition times during development. Open access is an emerging model of open innovation that places no restriction on the use of information and has the potential to accelerate the development of new drugs. ⋯ Results demonstrate that openly sharing the JQ1 molecule led to a greater uptake by a wider and more multi-disciplinary research community. A comparative analysis of the patent landscapes for each candidate also found that the broader scientific diaspora of the publically released JQ1 data enhanced innovation, evidenced by a greater number of downstream patents filed in relation to JQ1. The authors' findings counter the notion that open access drug discovery would leak commercial intellectual property. On the contrary, JQ1 serves as a test case to evidence that open access drug discovery can be an economic model that potentially improves efficiency and cost of drug discovery and its subsequent commercialization.
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Expert Opin Drug Discov · Oct 2015
ReviewEmbracing synthetic lethality of novel anticancer therapies.
The significant challenge posed by cancer to human healthcare has led to the exploration of new approaches to combat it. Synthetic lethality (SL) is one such emerging area in the development of novel anticancer therapies. SL can be described as lethality (cell death) resulting from the combination of the two mutations, wherein the mutation in either of the two codependent genes in normal or cancer cells is viable. This concept is specifically being exploited in cancer research for selectively targeting specific tumor cells. ⋯ Most of the currently used chemotherapeutic agents will destroy cells irrespective of whether they are cancer cells or fast growing normal cells; but SL is one of the approaches being developed with potential as a selective cancer therapy. PARP inhibitors, such as olaparib, are useful in BRCA mutated cancer cells and are also used in combination with other drug to enhance their efficacy. Research on PARP inhibitors is progressing at a good pace but there are still some significant challenges that must be addressed.
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Expert Opin Drug Discov · Jul 2015
ReviewAnimal models for ebolavirus countermeasures discovery: what defines a useful model?
Ebolaviruses are highly pathogenic filoviruses, which cause disease in humans and nonhuman primates (NHP) in Africa. The Zaire ebolavirus outbreak in 2014, which continues to greatly affect Western Africa and other countries to which the hemorrhagic fever was exported due to travel of unsymptomatic yet infected individuals, was complicated by the lack of available licensed vaccines or therapeutics to combat infection. After almost a year of research at an increased pace to find and test vaccines and therapeutics, there is now a deeper understanding of the available disease models for ebolavirus infection. Demonstration of vaccine or therapeutic efficacy in NHP models of ebolavirus infection is crucial to the development and eventual licensure of ebolavirus medical countermeasures, so that safe and effective countermeasures can be accelerated into human clinical trials. ⋯ Animal models of EHF varying from rodents to NHP species are currently under evaluation for their reproducibility and utility for modeling infection in humans. Complete development and licensure of therapeutic agents and vaccines will require demonstration that mechanisms conferring protection in NHP models of infection are predictive of protective responses in humans, for a given countermeasure.