RCC - The sneaky disease

It's no wonder that the problems in dealing with RCC seem so intractable, when you read information like that in the article I've copied below. However, it serves to show the immense effort being made world-wide and the rapid and solid progress now being made. (Another example is the sterling efforts at developing a universal cancer vaccine currently going on in Israel.)

The BBC's Horizon science programme had an episode screened last night entitled "Defeating Cancer". It showed treatment of 3 patients at one of the UK's most notable hospitals for cancer research and pioneering treatment (The Royal Marsden). All three were doing well, one after Cyberknife radiotherapy, one after da Vinci robotic surgery and one on a new targeted therapy (Vemurafenib, marketed as Zelboraf) for advanced metastatic melanoma (the other cases were prostate cancer).

I've been following up on some info emerging from the Horizon programme and it has led me to some interesting material, such as that below. The seeming intransigence of kidney cancer when attacked with the latest cleverly 3D-designed drugs, is explained to a great degree by the following:


Cancer genes differ in different parts of a tumour

15 March 2012

Taking a sample from just one part of a tumour may not give a full picture of its ‘genetic landscape’, according to a landmark study published in the New England Journal of Medicine this month.

The findings could help explain why attempts at using single biopsies to identify biomarkers to which personalised cancer treatments can be targeted have not been more successful. They also point to a way forward.

Cancer Research UK scientists carried out the first ever genome-wide analysis of the genetic variation between different regions of the same tumour using kidney cancer samples. They found that around two-thirds of gene faults were not shared across other biopsies from the same tumour.

The tumour samples analysed in this study were donated by patients with advanced kidney cancer treated at The Royal Marsden under the supervision of Dr James Larkin.

Dr Larkin said: “The idea of personalised medicine is to tailor treatments to suit individual patients. This study in kidney cancer has shown significant molecular changes between different parts of the same tumour. We have also seen differences between primary kidney tumours and cancer cells that have spread to other organs. This may be relevant to how we treat kidney cancer with drugs because the molecular changes that drive the growth of the cancer once it has spread may be different from those that drive the growth of the primary tumour.”

Professor Charles Swanton, based at Cancer Research UK’s London Research Institute and the UCL Cancer Institute, said: “We’ve known for some time that tumours are a ‘patchwork’ of faults but this is the first time we’ve been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumour in such exquisite detail.

“This has revealed an extraordinary amount of diversity, with more differences between biopsies from the same tumour at the genetic level than there are similarities. The next step will be to understand what's driving this diversity in different cancers and identify key driver mutations that are common throughout all parts of a tumour."

The researchers compared the genetic faults in samples taken from different parts of four separate kidney tumours, and also from sites where the cancer had spread to other organs.

This allowed them to identify 118 different mutations.

40 of these were ‘ubiquitous mutations’ found in all biopsies.
53 were ‘shared mutations’ that were present in most but not all biopsies.
25 were ‘private mutations’ that were only detected in a single biopsy.
By analysing the location of shared mutations in relation to the whole tumour, the researchers were able to trace the origins of particular subtypes of cancer cells back to key driver mutations. This allowed the scientists to create a ‘map’ of how the pattern of faults within the tumour might have evolved over time.

Professor Swanton added: “For the first time we’ve been able to use the pattern of genetic faults in a tumour to trace the origins of certain populations of cancers cells, much in the same way as Darwin used his ‘tree of life’ theory to show how different species are related.

“This underscores the importance of targeting common mutations found in the ‘trunk’ of the tree as opposed to those found in the ‘branches’, which may only be present in a relatively small number of cells. It may also explain why surgery to remove the primary kidney tumour can improve survival, by decreasing the likelihood that resistant cells will be present that could go on to re-grow the tumour after treatment.”