Letters from the lab: Oncology

Oncology Biology Scientist at MedImmune: Immune Mediated Therapy of Cancer

I am part of the Oncology Discovery team at MedImmune. We support our biologics programmes from inception through clinical trials to life cycle management. At the birth of a programme we provide a deeper understanding of the basic science associated with a potentially important target through in vitro and in vivo studies. Throughout lead isolation and optimisation we provide screening and characterisation assays to guide the choice of lead antibodies, and the subsequent pharmacology studies to support the nomination of our clinical candidate drugs. We continue to support our programmes throughout late stage preclinical and then onto clinical development, all the way up to pivotal phase III trials, by generating and testing combination and dosing hypotheses in preclinical models in order to support focussed clinical development plans.
 
My personal area of interest is in Immune Mediated Therapy of Cancer (IMTC). IMTC encompasses a range of therapeutic approaches that all aim to harness the immune system to fight cancer. One of MedImmune’s areas of emphasis is to partner with the patient’s own immune system to recognise and eliminate cancers by modulating T cell activities. This approach is exciting because of the great potential benefit to patients that lies in harnessing the flexibility and power of the immune response. Because the immune system is capable of recognising many different targets, it is able to respond to a large range of cancers. This makes T cell enhancement a broadly applicable therapeutic approach and clinical activity has already been observed in melanoma, prostate cancer, renal cancer, lung cancer and other settings. In addition, because the immune system can remember previously encountered antigens, with the potential to adapt to changes in the antigens it sees over time, T cell enhancement has the potential to deliver step-changes in survival to some patients; with a reduced chance of acquired resistance to treatment.
 
AstraZeneca/MedImmune is at the forefront of this promising new area, with programmes covering the breadth of our research and development effort, targeting different aspects of T cell biology. One of the most exciting things about this breadth of investment is the opportunity for the biology group to work closely with our colleagues in translational and clinical medicine. One of the significant challenges will be to understand and predict responses to such therapies, and we are applying resources across our organization to increase the probability that our clinical stage programmes will be successful. At the same time we are capturing valuable information about disease biology and patient responses from the clinic and using this information to empower our earlier programmes to strengthen them and increase their value. Furthermore, we have developed strong relationships with academic experts in Immune Mediated Therapy of Cancer from across the world.  This collaborative way of working puts us in a strong position to successfully deliver life changing medicines to patients.

 

Director of Clinical Research: the development of Caprelsa (vandetanib)

As a Director of Clinical Research for AstraZeneca oncology, I am responsible for the clinical development of Caprelsa (vandetanib). My previous experience of over ten years at the National Institutes of Health in basic science research, cancer surgery and participation in cancer clinical trials provides an important foundation for this work.

AstraZeneca has been working for many years to better understand the science behind cancer and develop therapies based on the knowledge gained through oncology studies. As our understanding of the molecular mechanisms in cancer improves we have been able to more precisely match the patients with the most effective therapy based on the molecular biology of the tumor. Clearly the way forward is to continue to drive our understanding of individual tumor types and the development of treatments that specifically target those tumors.

Our oncology researchers work closely with experts outside of our own labs to propose, design and support clinical trials. The purpose of this is not only to test new cancer medicines, but also to explore additional indications for the medicines we have already brought to market. Based on our growing knowledge, we are increasingly evaluating our medicines in combination with other treatments that are on the market or in development. Collaborating on a global scale with both basic scientists and researchers inside and outside of AstraZeneca has greatly enhanced our ability to understand in which tumors Caprelsa (vandetanib) will likely have the most benefit.

Caprelsa (vandetanib) is the first approved treatment for patients with advanced medullary thyroid cancer in Europe and the United States. Advanced medullary thyroid cancer is a rare disease with a poor prognosis and clinical outcomes for patients with this disease have not changed substantially in the past 20 years. Helping to bring this medicine to market meant that physicians had to go beyond localised therapies such as palliative surgery. We’re not stopping there. We continue to research vandetanib to see if it has the potential to help people with several other types of cancers, including specific mutations of lung cancer, papillary thyroid cancer, pancreatic cancer and liver cancer.

The most satisfying thing about this type of cancer research is being able to apply the most recent scientific knowledge directly to the drug development process. From the study design concept, trial design, through to trial results interpretation, it is important that patients and physicians have access to the novel cancer therapies.

In the future, I think we will see cancer treatment becoming more commonly based on the molecular profile of a cancer. This may be to the extent that the “type” of cancer becomes irrelevant and decisions are based on the molecular biology of the cells.

Vice President of Oncology Innovative Science: The latest from Waltham’s oncology progress

Cancer still represents an area of high unmet medical need. Although over thirty new medicines have been approved since 2005, most patients with common cancers still die from their disease. In addition, global cancer incidence will increase 27% by 2020, with significant growth in Asia from ageing populations, the smoking epidemic and unhealthy lifestyles. Our ambition is to redefine the cancer problem, discover new therapeutic solutions based on expanding disease knowledge and ultimately to make a meaningful difference to patients.

Today we are fortunate to be working in a period of transformation in oncology research and drug development. Over the past decade the academic, clinical and industrial sectors have delivered significant technological advances. These are enabling a new strategic focus on targeting the molecular drivers of disease. We are shifting our focus from the classic definition of the disease (cancer histology), to an understanding of the molecular characteristics. Large public initiatives have laid the foundation to enable genomic classification of patient’s tumors, in real time, influencing treatment decisions and driving the discovery of new drug targets. At its core, our strategy is ‘patient-driven’ drug discovery and development. Our new drug targets, preclinical disease models and ultimately our clinical trial design are all driven by a molecular understanding of our patients.

AstraZeneca oncology is focusing on five disease areas including lung, breast, gastrointestinal, urology and hematology. Where I am based in Waltham, U.S., we have been able to assemble a great team of scientists. Their research is directed towards the hematological cancers, breast and lung cancers with an emphasis on novel genetic drivers of disease. The wealth of patient genetic data presents us with an unparalleled opportunity to discover medicines that deliver a step change in the treatment of disease and ultimately save patients lives.

Vice President and Head of Innovation Center China: Our oncology research in Asia

I am based in Shanghai and head up the Innovation Centre China (ICC). The ICC focuses on the benefit and value of innovative medicines for Chinese patients, with a big focus on cancer.

We have several areas of focus within our oncology research in Asia. For cancers that affect us on a global scale, such as lung cancer, we need to examine any differences in reaction to treatment based on ethnicity. In addition, we have a focus on some of the cancers that are more prevalent in Asia such as gastric and esophageal.

I really feel Asia is an important place to be researching oncology. First of all, there are still huge unmet medical needs here – particularly in the more prevalent cancer types. AstraZeneca also has in-depth knowledge of the region to go with that, a fantastic team of scientists. We’ve also had some great breakthroughs – Iressa, a drug for lung cancer, was first approved in Asia.

During the last few years, we’ve also made some great collaborations within local science communities. It’s been particularly useful in terms of Iressa and how it can best suit patients in Asia. We continue to learn from the Iressa drug and further improve our general understanding of the diseases in Asia. We are using this to guide our research effort with the goal to discover and develop new drugs that continue to benefit patients.
Of course, we also have our challenges. Similar to the situation to the rest of the world, the regulatory requirement is different among the major countries in the region, which makes our planning for research and clinical development complex and difficult to coordinate.

What really excites me is that AstraZeneca has established a significant R&D presence in Asia, with a strong focus on discovery. We also have development capabilities in Japan and we are continuing to strengthen those in China. AstraZeneca has a strong oncology portfolio, a good scientific reputation and commercial power in the region. For the last few years we’ve been building a strong Asia alliance network and we expect R&D capabilities to further improve. More novel agents, research tools and new therapeutic concepts will come from this part of world and AstraZeneca is well positioned to drive this.