Guest article

We must reevaluate disease links to create more effective and profitable therapeutics

By Dr H Michael Shepard

- Last updated on GMT

© GettyImages/image_jungle
© GettyImages/image_jungle

Related tags: Inflammation, Autoimmune disease, Cancer, COVID-19, Rheumatoid arthritis

Therapies for cancer, autoimmune diseases, inflammatory diseases and other drug markets are all siloed, despite new research emerging that shows potential connections between them. In order to create more effective therapeutics, we need to pull from research in these different areas, identify the underlying commonalities and target these links, argues Dr H Michael Shepard, CEO and cofounder of Enosi Life Sciences, in a guest article.

New therapeutics are being researched daily, with development and manufacturing taking place all across the globe. Scientists are constantly testing new approaches, delivery methods, classical chemical compounds and antibodies that offer more effective solutions for improving patient outcomes while also seeking a profit to ensure program continuation.

Continued research and development has left scientists in narrow channels with a highly targeted focus on a research topic or an individual disease category. This has a lot to do with how grants are awarded in academic institutions where novel research has to be done with ‘left-over’ grant money. In other cases, unique ideas find their first funding in start-up biotechnology companies.

Still, scientists are expected to stay inside the lines of their own practice, no matter how novel their advancements may be. Scientists and clinicians focused on cancer will rarely undertake autoimmune disease research, and vice versa – making it difficult for new technologies to be shared widely across fields.  

Inflammation is present in many diseases and could be the thread that ties all of them together​ 

The enhancement of artificial intelligence, combined with very large-scale sequencing of the genome of many patients, has led to the Age of Big Data. Algorithms have been developed that enable connections that were once unthinkable, allowing scientists to see beyond their silos. A simple web search can link almost any disease with a set of genes and reveal what diseases have been associated with alterations in that gene. For example, during COVID-19 research, scientists are being forced out of silos because of their usage of big data algorithms to find relationships.  This data informs a treating physician that a therapeutic that may benefit their patient already exists, even if it was developed for an unrelated ailment.

While these technologies have empowered research like never before, they cannot fully replace the value of the tried and true – attending scientific meetings. Almost 40 years ago, I attended a scientific meeting of immunologists in Germany, studying how cancer cells evade the immune system. Immunology is a branch of science that is associated with almost all diseases, so there was a diverse group of scientists present. I met Marc Feldmann there; he who told me about rheumatoid arthritis (RA) and his hypothesis that the immune signaling molecule called tumor necrosis factor (TNF) may be an important trigger for that disease. Because our own early data suggested that tumor cell resistance to TNF-mediated killing allowed them to escape immunity and grow, we found that we could share very different views on what TNF does. We have since learned that experimental cancer drugs could also be active in mouse models of rheumatoid arthritis, and in addition to having TNF as a driver, there are other common aspects shared by RA and cancer. 

Connection between autoimmune diseases and cancer 

We began looking deeper into the cancer and autoimmune disease connection and discovered that a connection between autoimmune diseases and cancer​ is present. Researchers have found associations between 23 different autoimmune and chronic inflammatory autoimmune-related diseases and malignancy. Even more concerning, autoimmune diseases that affect multiple organs show associations with the development of focus types of cancer​. Other research has acknowledged similarities between cancer and autoimmunity​. There’s no denying that these two diseases are interconnected.

Inflammation is present in many diseases and could be the thread that ties all of them together. For example, new research suggests that TNF may be the key driver of lung inflammation as a result of COVID-19 infection. Similarly, chronic inflammation is associated with development of Alzheimer’s Disease, while it has also been found that TNF drives the proliferation of cancer cells - just the opposite of what many initially thought.

These are just a few examples, out of many, but they offer a framework for how we can find these links and move forward in our approach to treatment and drug development in the 21st century. Big Data allows much of this research to actually start on a computer and then proceed to well-defined laboratory experiments. This has the potential for big cost savings for drug discovery.

Patient outcomes will remain a priority for many researchers, but therapeutics also need to have potential for profit to justify the investments that will take them from early stages to clinical trials to commercialization.

Reevaluating these links could offer cost savings for pharmaceutical companies and patients alike, while still providing good returns for investors. This is important because by 2040, the number of new cancer cases per year is expected to rise to 29.5 million and the number of cancer-related deaths to 16.4 million, according to estimates from the International Agency for Research on Cancer (IARC). Furthermore, approximately 4% of the global population is impacted by autoimmune diseases, totaling almost 312 million people, as per data from the US National Stem Cell Foundation.

Now more than ever we need to identify the underlying links and provide support to the researchers and clinical investigators that are looking for novel and more effective drugs. The more we employ new technologies for drug discovery and emerge from our silos, the sooner we will discover new drugs and improve patients’ lives.  If we’re able to do so, we may experience a pharmaceutical revolution that can improve clinical outcomes for many currently underserved populations.

Studies referenced in article 

Franks, A. L., & Slansky, J. E. (2012). Multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases and cancer. Anticancer research​, 32​(4), 1119–1136.

Simi, A., Rahat, M.A., Shakya, J (2016) Parallel Aspects of the Microenvironment in Cancer and Autoimmune Disease; Mediators of Inflammation; https://doi.org/10.1155/2016/4375120 0962-9351

Enosi-Portrait-DrHMichaelShepard

Dr H Michael Shepard is a global, leading authority on cancer research and therapeutics. He is best known for his invention of Herceptin/Trastuzumab, which has remained one of the most profitable platforms for Roche (>US$7bn). He has had many successful ventures in this field—working at Genentech (sold to Roche - US$46.8bn), Canji, Inc (bought by Scheirng-Plough) and Halozyme (now valued at US$2.6bn). He is a widely acknowledged biomarker pioneer and recognized worldwide. He received the 2019 Albert Lasker Award and the Warren Alpert Prize, among many other professional accolades. 

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