Top 10 Research Fronts in Medicine in 2018

Cancer Therapies including PD-1/PD-L1 Inhibitors, etc. Being the "Hottest"

The 2018 Research Fronts report has recently been released jointly by the Institutes of Science and Development, Chinese Academy of Sciences, National Science Library, Chinese Academy of Sciences, and Clarivate Analytics together with 2018 Research Front Hotness Indexes report, which includes top 10 research fronts in clinical medicine and 11 emerging research fronts in clinical medicine (Table I). Here, I’d like to interpret points therein closely linked with the pharmaceutical industry one by one.

Table I Top 10 Research Fronts in Clinical Medicine and 11 Emerging Research Fronts in Clinical Medicine

Drug hotspot I: PD-1/PD-L1 inhibitors

From Table I, we can see that PD-1/PD-L1 inhibitors are selected among both 2018 research fronts and emerging research fronts in clinical medicine, being the "hottest among the hot". Many PD-1/PD-L1 inhibitors have successively been approved for marketing in the world in recent years, including nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab, which are used to treat many cancer diseases like lung cancer and skin cancer, with efficacy incomparable by other drugs.

As PD-1/PD-L1 inhibitors show enormous advantages in oncology treatment, many Chinese pharmaceutical enterprises have competed to develop such drugs, for example, Hengrui Medicine, Junshi Biosciences, and BeiGene all have leading products in development. The major drawback in the use of PD-1/PD-L1 inhibitors from the perspective of the current market is the expensive prices. In the future, Chinese-produced PD-1/PD-L1 inhibitors will hopefully solve this issue and be more affordable.

Drug hotspot II: The two monoclonal antibody drugs: infliximab biosimilar CT-P13 and tocilizumab

Infliximab (its biosimilar is CT-P13) is an antibody drug developed by the Swiss company: Cilag AG, which is approved to treat diseases like Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and ulcerative colitis as it can selectively block TNF-α inside patients, reduce inflammatory response caused by TNF-α to relieve symptoms, and inhibit joint tissue damage and bone erosion. Marketed in China in September 2007, the drug is a product of Xian Janssen Pharmaceutical Ltd.

Tocilizumab is a monoclonal antibody drug used to treat rheumatic arthritis. It was first approved by FDA for marketing in January 2010 and is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF agonists.

Drug hotspot III: Breakthrough new drug for idiopathic pulmonary fibrosis—Nintedanib

Fig. I Structural Formula of Nintedanib

As a small molecule tyrosine kinase inhibitor (Fig. I) developed by Boehringer Ingelheim, nintedanib is approved to treat idiopathic pulmonary fibrosis (IPF) and non-small cell lung cancer (NSCLC).

As a serious lung disease, IPF is mainly characterized by proliferation of fibroblasts in lung, and gathering of a large number of extracellular matrices accompanied with inflammatory injury and lung tissue structure damage. IPF is very difficult to treat as its progression is unpredictable. Patients generally only have 2-3 years of survival time, with five-year survival rate less than 30%. Research has proved that nintedanib can stop IPF by competitively inhibiting receptor tyrosine kinases such as fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor, and vascular epidermal growth factor receptor.

Drug hotspot IV: Opioid crisis

Trump made rash criticism against China when mentioning the U.S. opioid crisis some time ago, which aroused great controversy, however, in fact, opioid crisis is a global problem that does not only exist in the U.S., but also in China, Europe, and most countries and regions in the world.

Countries have input heavy human and financial resources to deal with the opioid crisis, for example, the budget of the 21st Century Cures Act signed by Obama in December 2016 specially provided USD 1 billion new fund to combat opioid epidemic; Trump founded the "Commission on Combating Drug Addiction and the Opioid Crisis" in March 2017 by signing an executive order, to investigate how to deal with damage caused by drug abuse, addiction, and opioid crisis; the U.S. also officially listed opioid crisis as a "national emergency" in August 2017. And countries like China have developed anti-abuse preparations to prevent opioid abuse.

Drug hotspot V: Venetoclax, an "Australian anticancer miracle drug"

Venetoclax is a BCL-2 inhibitor developed by Walter and Eliza Hall Institute of Medical Research in Australia. It is a new targeted drug mainly used to treat chronic lymphocytic leukemia patients who have del(17p) mutation and have received at least one prior therapy. It has been fast approved by the U.S. FDA and the EU, and is called an "Australian anticancer miracle drug".

Drug hotspot VI: Immune inhibitors for atopic dermatitis

Atopic dermatitis is a common skin disease of children and adolescents, with incidence of about 3% in China. The disease often complicates certain genetic or allergic diseases such as allergic rhinitis and asthma. From the perspective of incidence, atopic dermatitis patients are young and have diverse forms of skin lesion, complex conditions, and intense pruritus which seriously affect patients’ work and life. As each atopic dermatitis patient varies much in terms of disease severity, accompanied disease, and age of onset, they are generally treated individually by disease severity (Fig. II).

Fig. II Treatment of Atopic Dermatitis by Severity

We can see from the above figure that immune inhibitors will be used only when the atopic dermatitis is severe, which mainly include glucocorticoids such as desonide; calcineurin inhibitors such as tacrolimus and pimecrolimus; and selective immune inhibitors such as cyclosporin and mycophenolate mofetil. Glucocorticoids are the clinical drug of choice from the perspective of clinical use, however, their big side effects largely restrict their extensive use. Researchers have been working on new, efficient, low-toxicity atopic dermatitis drugs in recent years.

Summary

From the above analysis, we can see that cancer therapies including PD-1/PD-L1 inhibitors are currently the hottest directions in the field of medicine, with recent developments frequently reported. Among cancers, cancers with a large number of patients such as lung cancer, leukemia, and colorectal cancer have been researched more. The above hotspots also show the greatest advances of the medical world in recent years, which have been used for disease treatment and achieved great breakthroughs.

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