This year’s Cold Spring Harbor Laboratory meeting was attended by researchers from the BCI, including Dr Ping-Pui Wong and Professor Kairbaan Hodivala-Dilke from the Adhesion and Angiogenesis lab.

The conference, entitled Cancer Biology and Therapeutics, covered major cancer research topics including:

Tumour heterogeneity - the phenomenon of tumours not consisting of a uniform mass, but a number of areas with very different characteristics. This is an important concept for research, drug design and medical care alike, because understanding the inner workings of tumours will inform the development of more effective treatments. Here’s an interesting article exploring some aspects of heterogeneity, and some further reading on its causes and consequences.

Diagnostic imaging and drug delivery –the invention of better imaging technologies has not only improved diagnostics, but ongoing tumour responses to therapy can also be monitored, without invasive surgery and reliance on observing symptom changes that can provide only limited information. See our recent post on Dr Marshall’s grant to develop a drug delivery system and imaging agent.

Signaling networks and therapeutics – tumours don’t grow in isolation; just like the rest of our cells, they talk to each other and the environment, and receive messages back that can change their behaviour. Integrins are a focus of our Tumour Biology department because they are major signalling molecules. Understanding cellular chit-chat can lead us to new therapies as we learn how to change those conversations and interrupt damaging instructions.

Other topics covered included epigenetics, metabolism, and the microenvironment: an increasingly scrutinised area of research, one talk on the topic was given by Professor Rakesh Jain, whose work is well-known to many angiogenesis researchers.

His points included:

• Tumour blood and lymphatic vessels are structurally abnormal – they create a hostile tumour biochemical and mechanical microenvironment (including hypoxia – lack of oxygen; high interstitial fluid pressure; high shear stress).
• These tumour micro-environment characteristics fuel malignant properties of the tumour and prevent efficient drug delivery.
• We could – instead of the original destroy the blood vessels intention – develop a number of strategies to normalise blood vessels - improve blood vessel structure, blood flow rate, oxygen levels. See last year’s PNAS paper by Huang et al. on the subject for more on modifying the immune tumour environment.

From Huang et al. 2012: modifying doses of anti-angiogenic drugs to alter the tumour immune environment. Low doses of these drugs, such as VEGF receptor 2 inhibitors, can normalise the vasculature and stimulate both macrophages (TAMs) and T cells to perform anti-tumour immune activities, as well as provide better drug accessibility to tumour cells via improved blood flow. Conversely, high doses can cause a cascade that impedes anti-cancer treatments, such as vaccine therapy.

Further points:

• Single cell diversity may have an effect on tumour heterogeneity – we’ll need more sensitive epigenetic studies.
• Better experimental design – we should co-culture tumour cells and fibroblasts (normal cells in the microenvironment that can turn to assist the tumour) before implanting them to recreate tumour microenvironments in vitro and in vivo.
• Better design of clinical trials – targeting subtypes of cancer patients, small scale phase II trials.

Other talks highlighted by Dr Wong included Professor Robert Vonderheide, who spoke about immune cell involvement (specifically T cells) in pancreatic cancer, and Professor Ronald Evans who discussed the effect of vitamin D on the pancreatic tumour microenvironment; a subject that Dr Fieke Froeling, a previous student in Dr Hemant Kocher’s group, published on in 2009.

Professor Hodivala-Dilke also presented at the meeting about ongoing studies in the Adhesion and Angiogenesis group, led by Dr Tavora, investigating how a protein downstream of integrins called FAK (focal adhesion kinase) appears to be involved in tumour chemoresistance. This abstract will also be presented at the BACR meeting in Bristol next month.

Many thanks to Dr Wong for his CSH images and notes from the meeting.