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Welcome

F. Lordick (Germany)

SlotAZ-1 Introduction

Florian Lordick introduces the symposium, about the mechanisms and biology of angiogenesis in cancer, highlighting the latest clinical trials of angiogenesis-targeting therapies in GI malignancies and investigating how patients can benefit from different treatments.

Transcription

Disclosures statement

You can show the next slide – this is just to show you my disclosures.  Every speaker will show his disclosures in this topic.

Full transcription

Full transcription

Disclosures statement

You can show the next slide – this is just to show you my disclosures.  Every speaker will show his disclosures in this topic.

Learning objectives

And we really designed the programme and the talks of this symposium according to the following learning objectives; to understand the mechanisms and biology of angiogenesis in cancer in general and to be aware of the latest clinical trials investigating angiogenesis-targeting therapies in GI malignancies; to understand which therapies or treatment combinations produce optimal patient outcomes and to understand which patients would benefit from the latest developments and how to optimise their management in daily clinical practice.

Elsevier’s Advances in Gastrointestinal Cancer Resource Centre

This symposium is also meant as something like a kick off symposium for the following platform.  It is galled the gastrointestinal cancer resource centre.  This is something that you find from now on on the web, it’s a website which is organised by Elsevier, a very famous and important publisher and on this website you can find the latest developments in gastrointestinal malignancies. 

There is a faculty and editorial board.  I am a member of that and also Professor Ian Chau is a member of that and some other persons.  We take care that actual news, developments are uploaded on this platform like open access articles, patient case reports, interviews, lectures and so on.

You can access this web page by gastrointestinalcancer.elsevierresource.com and you are being invited to access this very, very interesting new resource centre.

VEGF signalling is an important pathway in angiogenesis

Which of these drugs target VEGFR-2?

Maybe we do a short training session to see if everything works and if you are a competent audience.  The first question is which of these drugs targets VEGFR-2:  option one, bevacizumab, two sorafenib, three regorafenib, four ramucirumab and five sorafenib, regorafenib and ramucirumab?

The voting is now open; probably we will hear some music.  [Pause for voting]

40% said all three drugs that are displayed here target VEGFR-2 and ramucirumab was elected by 33% and some voted for bevacizumab so just feel free to listen to the next talks and see if your answer was correct.

The why, the which and the how of targeting angiogenesis in GI malignancies

I will just give you a very, very short scientific introduction just to set the frame for the following speakers.

Tumour angiogenesis: in the beginning

In principle, and you may be aware of that, angiogenesis research is a relatively old historic topic and I put here a picture from a publication from 1939, so almost 80 years.  This was one of the first pictures I found about the investigation of tumour angiogenesis.

What you can see here is the implantation of an epithelial tumour into a transparent ear chamber of a rabbit.  You can see that epithelial tumour in the centre, located here and you can also see that from the margin of the ear chamber there are vessels sprouting into the direction of the tumour, so this is an interesting picture which tells us already what angiogenesis is about and this was published in 1939.

Tumour angiogenesis: in the beginning

Then there was important work from the laboratory of Judah Folkman who unfortunately died in 2008 and he also is shown in front of a nice picture.  This is not only art; it’s also showing angiogenesis and this is really what his life was about.

One of the members of our faculty, Professor Danesi, he worked with him and he will give some personal insights about what developed from his research and one of the things you certainly have heard about is the Folkman’s hypothesis.  It was really about the interaction between the cancer cells and the vasculature and Judah Folkman hypothesised that there must be soluble factors.  He called them TAF, tissue angiogenic factors that are part of this interaction of this cross talk between tumour cells and the tumour stroma and the tumour vasculature.

Tumour angiogenesis:  complex network and treatment targets

Meanwhile, the picture is much more complex and we know it’s not only one tissue angiogenic factor; it’s a whole system including different receptors which are displayed here and different cytokines and it’s a very complex and interesting system which is also actionable, drugable for a variety of drugs which are displayed here.  You will hear about the different mechanisms of action and clinical use of this network and of the drugs in the following talks. 

Anti-angiogenesis: complex network and treatment targets

There are different approaches to how you can manipulate the pathologic tumour vasculature.  One approach is destruction exerted for instance by some flavonoids.  The most commonly used approach is pruning, modification of the tumour vasculature which goes more into the direction of the normalisation of the tumour vasculature.

Another more experimental approach is the promotion of tumour angiogenesis exerted by drugs like for instance cilengitide, verapimil but this is certainly more experimental and there is no proof yet in the clinic that this really works.

Anti-angiogenesis: colorectal cancer

What we really know is that anti-angiogenic treatment plays a role in many of the important GI diseases.  This is just an ESMO recommended treatment algorithm about advanced colorectal cancer and you can see that anti-angiogenic drugs like bevacizumab, aflibercept, regorafenib can be found in different treatment lines and different scenarios.  Professor Ian Chau will tell you the whole story. 

Anti-angiogenesis: gastric cancer

Professor Wilke will tell you the story about gastric cancer which is basically a story about ramucirumab which has a place now in the second-line treatment of advanced gastric cancer as you can see here in this algorithm that we published earlier this year.

Anti-angiogenesis: hepatocellular carcinoma

HCC is also an interesting disease where anti-angiogenic treatment plays a role, namely sorafenib which plays a role for advanced stage C HCC and it will be the task of Professor Bolondi to outline the current anti-angiogenic approach and new data in hepatocellular carcinoma.

From anti-angiogenic response to acquired resistance

We don’t know enough probably about resistance mechanisms but knowledge is increasing and I’m very curious to hear Professor Danesi’s talk about the mechanisms.  Probably he will also touch a little bit about resistance mechanisms which basically come from the tumour microenvironment.

Today’s agenda

This brings me back to the agenda.  We will start with Professor Ramano Danesi’s talk about targeting angiogenesis in various GI malignancies, pathophysiology, the theory behind.  We will have a short discussion after that and then we go to three more clinically-oriented talks; as outlined Hansjochen Wilke, gastric cancer; Ian Chau, colorectal cancer; Luigi Bolondi, hepatocellular carcinoma. 

We will have a discussion after that and then we will discuss two or a maximum of three cases so please feel invited to join the discussion, to be interactive and this will be the end of this nice symposium.