Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Melanoma’

The future of cancer research – Part 2

Boston: Fallowing on from yesterday’s post about learnings from the AACR-NCI-EORTC conference in immuno-oncology, today’s post focuses on learnings from non-immune R&D, namely monoclonal antibodies and TKIs.

We know that cancer is a very complex topic and that adaptive resistance is increasingly a huge focus, but where are the new developments in this area and what can we learn from them in order to improve outcomes?

Another key area to consider is therapeutic index, that is are we shutting down enough of an oncogenic target’s activity in order to ensure efficacy? We’ve seen this in the anti-angiogenesis field, for example, where many VEGF inhibitors failed before bevacizumab (Avastin) finally cracked the nut in colorectal cancer and shifted the needle in terms of improving overall survival. We are now seeing this happen in other areas too, which will be covered below.

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The future of cancer research – what I learned from the AACR Targets meeting Part 1

As cancer becomes increasing complex with adaptive responses to therapeutic intervention, so our knowledge and strategies for overcoming it must also adapt and improve. Immunotherapy – in several forms – is probably the hottest topic on the landscape at the moment with both checkpoint inhibitors and chimeric antigen receptor technology (CART) vying for air time and attention but where are these approaches going and how can we harness the immune system more effectively?

One of the things I like most about AACR meetings is that there are nearly always some strategic gems emerging from the scientist-physician thought leaders if only you stop to think about how the field can rapidly change by looking at the early patterns that are emerging.

Here’s the first part of a synopsis of what I learned at the recent Molecular Targets meeting in Boston, some of these findings may well have a major impact on cancer research over the next few years…

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ECCO 2013 Notes from the Road – Day 1

It’s been a long 14+ hours here on the first day of ECCO in Amsterdam and I’m starting to flag a little. The fun part of being in Amsterdam is renting an apartment, living like a local and cycling to/from the conference centre on rickety Dutch bicycles!

That said, having been aghast at the poor wifi and frustrated with nearly not being allowed in a key session over badge confusion, plus scheduling of multiple key sessions at once, we decided to make the best of it and be selective. This morning, for example, I ran from lung to melanoma to breast to the  poster hall and back again to a lung session. Pieter had the luxury of enjoying the prostate cancer session in comparison!  By 6pm the BMS corporate symposia on immunotherapy was out – the brain was dazed and jetlagged, the car needed fuel (preferably of the rocket variety) and also a glass of wine!

We will post some more detailed notes later, but today I wanted to offer some top line thoughts on some of the highlights:

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Translating Cancer Genomics into Personalized Medicine: Challenges & Opportunities

By on April 3, 2011

Today in the plenary session of the 102nd Annual Meeting of the American Association for Cancer Research (AACR), Lynda Chin from Dana-Farber Cancer Institute in Boston provided an excellent overview of the challenges and opportunities of translating insights from cancer genomics into personalized medicine that will benefit patients.

I unequivocally recommend listening to the webcast of the plenary when it is posted on the AACR website.

As Dr Chin stated at the start of her presentation, “cancer is fundamentally a disease of the genome.”  The goal of all cancer research is to make progress with prevention, detection and cure.

In the plenary presentation she highlighted some of the successes that have come from understanding the genome e.g. the knowledge of BRAF mutation in melanoma led to the identification of a target and development of a new drug in 8 years.  In addition to the development of novel therapeutics, genomics research has helped companies reposition drugs and she highlighted crizotinib as an example (move from C-Met to ALK inhibition in NSCLC).

These successes have “motivated researchers” according to Chin.  However, it is transformative new technology such as the next generation of sequencing technology that has heralded “a new era of cancer genomics.”  Massively parallel sequencing enables comprehensive genome characterization.

Not only has innovative new sequencing technology increased the throughput, but it has dramatically decreased the costs.  As Dr Chin noted, some have questioned whether cancer genomics is worth it?  She outlined some of the recent successes, such as BAP1 in ocular melanoma (see my previous post on this) as examples of its value.

Challenges remain such as the management of the vast amount of data that genome sequencing produces.  Data management, processing and storage remain issues, as does the need to develop a reference human genome against which a patient’s tumor profile could be compared.

And even when you find a mutation, the challenge is to separate the “drivers” from the “passengers.” This according to Chin requires a “robust statistical framework”.

Cancer signaling is not linear, but is a highly interconnected and redundant network, so it remains a big task to translate genomics into personalized medicine.  According to Dr Chin using mice as models to bridge the gap between sequencing and man may be the way forward in translating cancer genomics into personalized medicine.

Targeting BAP1 – a future targeted therapy for Uveal Melanoma?

Uveal melanoma is a common cancer of the eye that involves the iris, ciliary body and choroid.  It is a disease that hits 2000 people per year in the United States and is common in those over 50.  Standard treatment involves removal of the eye or radiotherapy. There is an unmet need for systemic drug therapy.

Mutations in the BRAF gene (a member of the Raf family that encodes a serine/threonine protein kinase) have been found in many skin melanomas.  In 80% of the cases, a single point mutation in exon 15 (T1799A) has been shown to occur.  Some new agents in development such as PLX4032, ipilumumab, GSK2118436 have shown promise in advanced skin melanoma, but research suggests that BRAF may not be the key to Uveal melanoma.

Henriquez et al, in a paper published in Investigative Ophthalmology & Visual Science showed that the T1799A BRAF mutation was only present in 9 of 19 iris melanoma tissue samples, but only in one case of uveal melanoma, suggesting differences in the genetic and clinical differences between the two.

Recently, two papers have been published that provide new insight into this intraocular cancer. In the December 2, 2010 issue of the New England Journal of Medicine, Van Raamsdonk et al, found mutations of either the GNAQ or GNA11 gene to be present in 83% of uveal melanomas that were sequenced (n=713).

Harbour et al, in the December 3, 2010 issue of Science reported findings of a frequent mutation of BAP1 in metastasizing uveal melanomas. They found that in 26 of 31 (84%) of uveal melanoma tumors they examined, there was a mutation of BAP1, the gene encoding BRCA1 associated protein 1 (BAP1) on chromose 3p21.1. The results published in Science, “implicate loss of BAP1 in uveal melanoma metastasis and suggest that BAP1 pathway may be a valuable therapeutic target.”

The data suggests that there may be multiple pathways involved in uveal melanoma.  It is promising to see translational medicine in action, with scientists seeking to understand the molecular basis of a disease so that targeted therapies can be developed.  Uveal melanoma only strikes a relatively small number of patients, but if a highly effective drug can be developed, this could be a market opportunity worth pursuing.

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