How to utilize academic research efforts in cancer drug discovery

KEYWORDS:

• Academic research
• pharmaceutical industry
• cancer research
• drug discovery

1. Introduction

The development of a new medicine requires tremendous investments not only in research time but also in financial resources. When a drug reaches the market it is always the culminating effort of a multidisciplinary research team which involves chemists, biochemists, computational chemists, molecular biologists, toxicologists, pharmacologists, biophysicists, medical doctors and many more. Nowadays, academic research provides great potential for additional fundamental research support and human resources that assists pharmaceutical industries. It remains crucial to efficiently utilize and optimize the global impact of academic research efforts in the field of cancer drug discovery research. Hence, we will look at the actual situation of academic research in relation to pharmaceutical industries and outline the potential avenues for better association between these two distinct, yet complementary research environments.

2. Cancer drug discovery: academic and industrial research

An excellent review regarding academic drug discovery was recently written by Everett [1]. In this review, the author highlights the importance of four main aspects of drug discovery. They are as follows: a) improved validation of targets; b) elimination of false hits during high throughput screening; c) improved quality of molecular probes; and d) acquisition of high-grade informatics infrastructure. This is not always possible in a smaller academic environment as the infrastructures and equipment required, as well as financial resources, are too often limited. The development of a medicine takes a huge financial investment. In fact, it is estimated that to bring a new drug to the market necessitates as much as $2.87 billion US [2]. This evaluation takes into account the costs of both tested and abandoned compounds during the investigation on the way to reach the final marketed drug [2]. For this reason, several organizations were created to pool the resources and capability of different academic drug discovery centers allowing collaborative state-of-the-art research activities. For example, there are the Academic Drug Discovery Consortium (ADDC, US) [3], the European Lead Factory (ELF, Europe) [4], and the European Cancer Organization (Europe) [5], to name only a few. The latter organization is involved in providing better clinical treatments and care for cancer patients, and works in partnership with several European societies, with 150 000 professionals in oncology. These organizations form a network of several research centers located in universities, hospitals, and in some cases pharmaceutical industries and, together pool specialists involved in cancer R&D from the discovery stage through all steps needed to bringing a drug to the market. As well, in many countries there are several well-equipped drug discovery facilities that provide the necessary infrastructure to support academic screening [6,7]. Accurate target identification, validation, and selection is a vital step for any drug discovery program [1,8,9]. The second most important step involves high throughput screening enabling researchers to swiftly identify active compounds, biological macromolecules such as antibodies, or even precise genes able to control specific biomolecular pathways. These first two steps are critical to launch any academic or industrial drug discovery program on solid bases. Otherwise, active compounds (hit identification) can also be obtained by other methods such as structure-based rational drug design, fragment-based drug design, in silico screens and others. Once identified, active compounds can be tested and further optimized through SAR studies towards a lead molecule. Then, the essential work begins with the evaluation of efficacy and safety of selected active compounds in appropriate animal models and also with the complete drug metabolism and pharmacokinetic (DMPK) studies needed to evaluate, not only metabolic pathways but also potential drug–drug interactions and elimination routes. These investigations must be done at the earliest stage of development.

An outstanding example of academic research structure was recently described by Jordan et al. [8]. In this paper, one can appreciate key essential conditions to maximized research impact and output in cancer drug discovery. First of all, it is crucial to gather a team of experienced researchers in medicinal chemistry, in vitro biochemistry and cellular biology, and computational science (chemistry and biochemistry). Secondly, it is stated that outsourcing offers cost-effective means to access complementary expertise and technologies without the need to invest in the required infrastructure, technology, and specialized personnel. It is well understood that many larger academic facilities already possess the required equipment and personnel to perform in-house all tests needed, but outsourcing is vital for smaller universities involved in the field. As exemplified by Jordan et al., in vitro drug metabolism/pharmacokinetics and crystallography does not necessarily need to be performed in-house. Outsourcing can also be used for the preparation of a drug candidate by a properly accredited organization (GLP/GMP). Additionally, not every university has a fully operational Technology Transfer Office (TTO) able to deal with drug discovery commercialization, so expertise in that area can also be outsourced. Likewise, for smaller drug discovery laboratories, expertise in intellectual property can easily be subcontracted to specialized patent agencies. Thirdly, proximity and/or cooperation between academia and hospital is also crucial for rapid drug development. For example, the colocation of the Manchester Institute Drug Discovery Unit with the Christie Hospital offers a unique site for the discovery and the evaluation of new drug molecules which have already proven successful [8]. However, the reality is not always as bright as that specific example. There are many small size drug academic discovery laboratories struggling to keep up with the rapid pace of technological development and associated cost. For smaller facilities, partnership with pharma is vital. In Canada, there are organizations that are dedicated to bridging university research discoveries with industry in collaboration with TTO. They provide essential support (financial, commercial, directional and even scientific) to further develop technological advances making them more attractive and ready for licensing/partnering with a relevant company. These entities were established to fill the known gap between early discoveries and industry and are particularly useful for small and medium size universities. They are university research commercialization companies as, for example, Aligo Innovation, MaRS Innovation, Sovar Society, Univalor and UILO (University-Industry Liaison Office). Of course, they are partners with the inventors, the university and pharmaceutical industry and will benefit from any commercial successes achieved through technology transfer.

In Asia, there are reports of success towards the search of targeted anticancer agents taking roots within local universities and through preclinical development into phase I clinical trials [10]. The main conditions for success are similar to bigger research facilities. They are 1) the availability of infrastructure; 2) interaction with health services; 3) network with a talent pool; 4) expertise in key complementary disciplines and, 5) funds from the private and public sectors. These conditions, if not properly implemented can impede R&D and delay innovation. Furthermore, Matter also indicated the need to recognize translational research as the main driving factor to innovation along with the researcher’s personal disposition to accept risk and failure associated with it [10].

As we can see, there is an indispensable link between chemistry/biochemistry, biology/microbiology, and medicine. Drug discovery and the development process in academia in collaboration with industry were thoroughly dissected by Nicolaou [11]. In his paper, Nicolaou presents several advantages of academic-industrial corporations including complementarity of academic/industrial expertise, new funding opportunities, acceleration of translational research, enriched education, and training, etc. [11]. As reported by Palmer and Chaguturu, today there are several opportunities for academic laboratories to partner with the pharmaceutical industry, such as AstraZeneca’s Open Innovation, Pfizer’s Centers for Therapeutic Innovation, GSK’s Tres Cantos Open Lab Foundation, Lilly’s Phenotypic Drug Discovery Initiative, Merck’s SAGE Bionetworks and Clinical and Translational Science Awards Program [12]. These financial resources promote greater academic-industrial interactions. However, there are also drawbacks such as an impediment for the diffusion of results, less fundamental research, obstruction of career development and job hunting for students caused by confidentiality agreements, time pressures, and milestone attainments, etc. [11]. In fact, many of these difficulties could jeopardize the future success of students involved with an academic-industrial partnership. So, it is important to keep in mind these hurdles and to make sure that the students are not penalized during the course of their studies. The reality is that academic drug discovery programs do not easily allow the integration of students and postdoctoral researchers. It is for that reason that many academic drug discovery units tend to work mainly with tenured staff members [8]. Thus, occasionally PhD positions are proposed to work on fundamental projects that are not directly linked to their main R&D portfolio [8]. In this fashion, the student trainees can publish and present their research work at scientific conferences. As a matter of fact, if well supervised, students can greatly benefit from working in a multidisciplinary research environment.

Dahling et al. also presents important considerations in order to reduce the risks inherent to academic preclinical drug discovery research program [13]. In this thorough analysis, the authors outline the best possible ways to streamline projects with more realistic yet broader definition of success with the objective of always keeping the project on the translational track. Finally, Huber and Kraut present the main drivers of innovation in cancer drug discovery that are vital to successful cooperation between academia and industry. They are 1) sharing lead compounds with academia; 2) predicting drug resistance to cancer drugs and 3) partnerships between companies to test drug combinations [14]. Once fully integrated, these key conditions could very well lead to better treatments and outcomes for cancer patients.

3. Conclusion

Today, bearing in mind the huge cost of cancer research programs much attention is given to improve the link between academic and pharmaceutical drug discovery laboratories. Open cooperation seems to be the key factor for a successful outcome. It necessitates not only the share of expertise, equipment and facilities but also the share of the financial burden towards the common goal of bringing a drug to the market. Furthermore, it is essential to bridge the gap between early stage drug discovery and the industry with specialized organization that dedicates their work in generating the necessary additional value to any drug or technological innovation. These organizations are particularly crucial to ensure the commercial development of anticancer drugs as it is a very costly endeavor.

4. Expert opinion

Traditionally, academic science was largely based on the ‘gift economy’ which is in drastic contrast with the ‘market economy’ driving the pharmaceutical industry. However, an important shift in philosophy occurred in academia that is now focused, not only on basic research, but also in the development of new therapies usually in collaboration with the pharmaceutical industry. We have seen that the integration of academic and industrial research presents challenges but still leads to great benefit to both research centers and ultimately to society. The recruitment of a pool of competent multidisciplinary scientists who will work in cooperation, not in isolation is a key step to efficiently utilize academic research efforts in cancer drug discovery. Early target identification and proper hit selection are crucial for success and, if necessary it can be performed using services provided by organizations able to perform high throughput screening. As well, state-of-the-art equipment and/or access to equipment through outsourcing/subcontracting is essential for academic research centers. Another key condition promoting academic-industrial cooperation would be the accessibility to hospital cancer units facilitating translational research activities. Also, essential is the creation of strategies for graduate student integration within the academic drug discovery program keeping in mind their success and confidentiality requirements. Last but not least, adequate financial support from a combination of public, private and industrial partners is of vital importance. On this point, it would be important to reform the grant application system by direct allocation of public funds to academic institutions (in proportion to its size) who will be responsible for its fair distribution within its walls. The objective of the institutions would be to support early career researchers giving them a chance to rapidly launch their independent research for at least five years. Thereafter, the institution would be responsible to maintain, diminish or withdraw support based on their accomplishments. It is understood that, at the beginning of the new system, the institution would support already established and successful researchers. Over a career, this would save years of research endeavors that are now lost in time-consuming grant application activities (writing/reviewing). Additional private and industrial funding opportunities would still be available to universities based on classic grant applications system. To further improve academic-industrial cooperation in cancer drug discovery programs, dollar-for-dollar matching of industrial financial contributions by cancer societies and/or the private sector would certainly allow more projects to be funded.

In recent years, an important shift in philosophy allows a blend of curiosity-driven and market-driven research activities within academic centers. This new thinking promotes active cooperation among all partners (academic, industrial and medical researchers as well as various sponsors and community representatives) involved in cancer drug discovery activities. We also see the creation of organizations that generate additional value around a technology and facilitate its commercialization. They provide indispensable support to further advance early drug discovery towards a strong partnership with pharmaceutical industry. This type of business could very well be the catalyst needed to promote and stimulate academic-pharmaceutical interactions. If not already available, it is a corporate model that can easily be established elsewhere. Globally, this would accelerate drug discovery processes and outcomes for the benefit of humankind.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgement

The author thanks the staff of the Bureau de liaison entreprise-université at UQTR for its guidance during the development of our technology.

Additional information

Funding

This paper was not funded.