introduction O

ver the past few years there have been significant advances in the treatment of many cancers, but much remains to be done and both large and small drug discovery and develop-

ment organisations are devoting sizeable resources to oncology research. A number of articles in this edition of DDWdescribe var- ious technical and organisational approaches to this activity. One author quotes from the IOQVIA Global Oncology Trends

2018 report which states that in 2017 global spending on oncology therapies reached $133 billion and in the five year period 2013-17, 63 new indications were approved. These figures are likely to be exceeded in subsequent years and that, plus the fact the environ- ment is becoming more competitive, means that return on invest- ment is under pressure, leading to a number of collaborative arrangements including mergers and acquisitions which our author describes as “the cure for going it alone”. He mentions several such arrangements, discusses the case for cancer vaccines and indicates possible future approaches, including the increasing evidence of a possible link between the microbiome and cancer. He also states that the massive amounts of data generated from both pre-clinical and clinical studies will need to be analysed efficiently and suggests that artificial intelligence (AI) is likely to play an increasing role in this analysis. In another article the authors describe an initiative aimed at

increasing the efficiency of the drug discovery/development process, ie by reducing the attrition rate whereby the majority of lead com- pounds fail at some stage in that process. Again, oncology is the ther- apeutic area concerned and again a collaborative approach has been adopted, this one between a pharmaceutical company, AstraZeneca, and Cancer Research UK. It is pointed out that drug discovery is increasingly informed by genomics and the overall objective is to increase understanding of how specific genes and genetic variations drive tumour growth and therapeutic resistance. With that under- standing it should be possible to identify novel targets. The approach is summarised by the authors thus... “Fundamentally we see the inte- gration of genomics, functional genomics and AI technology becom- ing a routine part of drug discovery”. The adoption of an immunotherapeutic approach to the treat-

ment of cancer over the last decade or so has contributed signifi- cantly to the improved survival rates from many cancers. In anoth- er article herein the authors describe recent studies which indicate the possibility of expanding the range of tumours which can be treated immunotherapeutically. The approach, which is described in some detail, relies upon getting “the two halves of the immune system” to work together. The ‘two halves’ which are integrated are innate and adaptive immune responses and results from pre-clinical and early clinical studies appear to confirm the validity and promise of this approach. In the last (Winter 2018/19) edition of DDWwe included an arti-

cle describing the advantages of 3D cell culture systems over 2D systems in that they have greater biological relevance when used, for example, in modelling for oncological and other diseases. In the current number of the journal, the advantages of 3D organoid cell culture systems as applied to cancer research are described. These systems can produce cell architectures that more closely resemble the human tissue microenvironment and are more phenotypically relevant. An example is given of the use of patient-derived stem cells from a glioblastoma multiforma brain tumour. Such a model should prove useful in screening potential drugs for the treatment

Drug Discovery World Spring 2019

of this, the most common type of pri- mary brain tumour. In the Fall 2018

issue we included an article


with an emerging paradigm of integrat- ed drug discovery and


companies with the objective of increas- ing numbers of can- didates in drug devel- opment pipelines. The authors conclud- ed that, despite some unresolved questions, the paradigm is “here to stay”. In this edi- tion there is a follow- up article in which the authors acknowl- edge that the com- plexities of these efforts should not be underestimated, but they state that this business model “is now being adopted and utilised”. We usually include articles in which advances in technologies

routinely used in drug discovery laboratories are discussed. In this edition improvements in the optical cell counting and characterisa- tion technique of flow cytometry are reviewed. Recent advances in system flexibility, throughput and multichannel detection enable more useful information to be obtained from phenotypically- diverse cell samples. The processes of drug discovery and development inevitably

involve individuals from a range of scientific and medical disci- plines working as teams, but opinions vary as to how formal the organisational structures of such teams should be. Intuitively there is probably a feeling that over-formality would impose constraints on creativity. In order to explore this in more detail the authors of another of our articles carried out a longitudinal study of five pro- jects in a pharmaceutical company. Their conclusions, given as rec- ommendations for team leaders, are that formal structures do play an important role in guiding more informal practices whereby more scientific knowledge is created, ie there should be the right balance between formal and informal structures. There is a recommendation from another of our authors to

“return to our roots via roots” by which she means that we should combine ancient observations on the medicinal use of plant-derived products with modern ‘molecular mining’ using the sequencing technology now available. This should enable the genetic and epi- genetic mechanisms in medicinally useful, or potentially useful, plants to be elucidated. It has been claimed that “all living plant species in the world would contribute to a greater chemical diversi- ty of bioactive compounds than any man-made chemical library”. As such, this could represent a rich and largely unexplored source of novel leads.

Dr Roger Brimblecombe PhD, DSc, FRCPath, FRSB 7

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