Biotech Strategy Blog

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

Posts tagged ‘MYC’

On the interaction between transcription factors and the immune system

We’re continuing our mini-series on the MYC oncogene and associated super-enhancers and transcription factors, with a look at some of the molecular mechanisms driving epigenetic accessibility and how they interact with the immune system. It turns out that the two appear to be inextricably linked.

Dr Jay Bradner (NIBR)

It’s an exciting and emerging area in oncology R&D as companies and researchers begin to leverage basic science with a convergence between scientific fields to drive new opportunities for therapeutic intervention in cancer.

Included in this post are excerpts from an interview with Dr Jay Bradner from the Novartis Institutes of Biomedical Research. He’s most well known for his academic research on chromatin and bromodomain fields. As Dr Bradner told me during our discussion:

“MYC has so many target genes that I would imagine one might find any number of immune factors as augmented in their expression by MYC.”

As always, we covered a lot of ground and dived into more detail. There’s also been a number of recent research papers published since our discussion that have shed more light on the topic.

This is the second post in our latest mini-series. If you’d liked to read this and our coverage from the forthcoming ESMO, SITC and ASH annual meetings, do sign up to keep up to date…

To learn more from our latest expert interview and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Through the window on the MYC oncogene

Through the window of aiming at tough to hit targets – with new approaches will we soon see more than before?

One of my big dislikes in oncology is the tendency to describe certain areas of R&D with the characterisation around the popular media epithet, “Drugging the undruggable.”

When we think of ‘undruggable’ in oncology R&D the first three targets that many people think of are MYC, RAS and TP53.

Quite aside from the issue that implies we can do little or nothing for those patients unfortunately affected is that it results in a more closed mind, a bit like half empty versus half full; it’s only undruggable in the context of what has gone before us and offers little in the way of future possibilities that lie ahead of us.

The RAS pathway is a great example of this phenomenon.

For years it was considered undruggable and yet despite that we now we have several selective BRAF mutation inhibitors, plus some nice approaches now emerging against KRAS mutations such as G12C (e.g. Amgen, Mirati, Araxes/J&J) and G12D, plus let’s not forget the potential for tipifarnib against HRAS mutant squamous cell carcinoma of the head and neck (SCCHN). All of these have shown some nice preclinical promise with some (BRAFV600E) already approved by Health Authorities.

There are other tough targets to think about too, including MYC and TP53, but rather than consider them undruggable, I’d rather think it just takes a little bit of time (and a lot research) before we understand the underlying biology better in order to figure what we can optimally target.

With that thought in mind, we have a new five part mini-series to share focusing on MYC. It’s actually been three or four years in the making ever since I heard a wonderful talk on the topic about improved mouse models that allow us to interrogate the biology more profoundly in order to understand how things work.

Not all of the interviews were theoretical in nature – we also talked to a leading scientist in this area involved in a largely unheard of start-up/spinoff with the goal of developing new therapeutic approaches against hard to target oncogenic drivers.

Before we go there on our journey, however, we need to begin with some basic understanding to set the scene…

To learn more and get a heads up on our latest oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

The Future of Multiple Myeloma

Happy New Year!

Immunotherapy treatment for multiple myeloma has been around for several decades, first in the form of stem cell transplantation, then augmented by the addition of IMiD immune modulation drugs such as thalidomide, lenalidomide or pomalidomide. In due course, along came immune checkpoint blockade in solid tumours and it was only a matter of time before they would be evaluated in hematologic malignancies, albeit with mixed results.

The proteasome inhibitors and IMiDs are unlikely to go away any time soon, but other targets have also emerged including CD38, SLAMF7/CS1, BCMA/APRIL, PD–1/L1 and a few others that are being currently investigated in the clinic.

Where does this leave us and what looks really promising?

In our latest thought leader interview undertaken at the recent American Society of Hematology (ASH) meeting in Atlanta, we asked a global expert for his candid views and were not surprised at some of the hard hitting comments that emerged from the in-depth discussion of several key issues…

To learn more and get a heads up on our latest KOL insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Commentary on ASH17 Day 2 in Atlanta

Snow at GWCCAtlanta – it’s day 2 of the annual meeting of the American Society of Hematology (ASH) meeting here in a chilly and snowy Atlanta.

I have to confess snow is not something we normally associate with southern States such as Georgia, but a cold snap has taken it’s toll on the ASH meeting, with many presentations cancelled as a result of travel delays.

Sunday at ASH is well known for the plenary session that takes place in the afternoon, but what else is hot at the meeting today? We’ve been talking to thought leaders, spending time in the vast poster hall and hearing some oral abstracts. There’s been been a surprising amount going on today at ASH in Atlanta.

If you are at ASH then you’ll know that all the sessions end at the same time, resulting in a massive movement of people as they go to the next session, as we saw today:

 

To get a heads up and further insights from ASH, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Key Highlights from Day 3 at AACR-NCI-EORTC TARGETS17

Philadelphia – Day 3 of the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics meeting continues to deliver on high quality talks with excellent data to discuss and parse.

Dr Jay Bradner (NIBR) at #Targets17

The session on epigenetics and transcription factors is always one of my favourites and this year didn’t disappoint.

There were also sessions on imaging, non-mutated genes, the tumour microenvironment and of course, a long poster session to browse.  Thankfully the poster halls weren’t as mobbed as they were at ASCO earlier in the year, but they were still pretty busy and well attended.

To learn more insights from this cancer conference, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Highlights from Day 2 AACR-NCI-EORTC #TARGETS17

Suburban Station, Philadelphia

Philadelphia – the second day of the AACR-NCI-EORTC molecular targets and cancer therapeutics meeting brought some new data to ponder.

I have to say it’s been the best molecular targets I’ve been to in may ways since 2009.

There were quite a few interesting elements here that cropped up during the day, which are well worth discussing and considering further implications.

To learn more insights on this intriguing topic, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Targeting MYC – the undruggable protein – or is it?

Have you ever sat in a freezing cold scientific session and been so engrossed in the compelling presentations that followed, you simply forgot to take notes? Not one. That actually happened to me at the American Association for Cancer Research (AACR) in Philadelphia this year in one of the many fringe sessions that I attended.

Reading Terminal Clock

Reading Terminal Clock, Philadelphia

Granted, the hot topic of the conference was undoubtedly checkpoint inhibition, but I was anxious to escape to the comfort of some meaty and familiar basic and translational science, namely MYC.  MYC is largely thought to be a difficult to target, even undruggable protein, and along with RAS and p53, represents a formidable challenge for cancer researchers.  These three oncogenic proteins alone are probably responsible for more drug resistance developing and even death from cancer than any other proteins in a patient with advanced disease.

For cancer patients with advanced disease, the clock is ticking on time they have left.

Solve these three problems (MYC, RAS and p53) and we may have a shot at dramatically improving outcomes. As Dr Gerard Evan (Cambridge) noted:

“I think it’s fair to say that we don’t really know why interruption of any oncogenic signal actually kills cancer cells, but one of the reasons that we’re interested in MYC is because it seems to be a common downstream effector of many, maybe all cancers.”

Sure, the road to success is paved with an enormous graveyard of failures, just as metastatic melanoma was before checkpoint blockade came along, ironically.  What I heard at AACR both inspired and filled me with greater confidence… we’re finally getting somewhere.

Subscribers can log-in to read our latest insights or you can purchase access to BSB Premium Content. 

This content is restricted to subscribers

How Syros are changing biotech R&D

We have written about small biotechs and big pharma a lot on this blog, particularly when they have exciting new developments in their pipeline to review and consider.  Increasingly, we have also begun to look at the early phase companies because often, that is where some fresh ideas and approaches are being developed and tested.

They’re also not beholden to the norm in terms of thinking that’s non-linear and many are academic start-ups that began life as thought leaders doing their own research and eventually VCs get interested, enabling financing to be raised.  The downside of this for some of our readers is that they’re usually not investable as a private company (sorry about that), but we have a broad church here on BSB and instead these small companies attract the interest of enlightened pharma companies who want to license early compounds in areas they are interested in or gain knowledge about a new field of research before buying elsewhere.  In other cases, the approach pays off in clinical trials and we see the IPOs emerge from companies such as Juno Therapeutics.

Syros Pharma LogoOne company that neatly fits this bill is Syros Pharmaceuticals, an academic spin-off from the Whitehead Institute of MIT and Dana Farber Cancer Institute in Boston based on the pioneering work of Drs Richard Young, Jay Bradner and Nathanael Gray.

Regular readers will remember our original article their the scientific work on gene transcription factors at AACR last year, which included a fascinating interview with Dr Young.  That was probably one of my favourite interviews of 2014 – I was inspired!

NancyHS201303wsdIt’s now time to look at the company and entertain some strategic thinking about where they’re coming from and where they’re going with clinical development.  The CEO, Dr Nancy Simonian, kindly agreed to an interview and be put in the ‘hot seat,’ so to speak.

This screenshot from the Syros website sums up their philosophy: Better medicines through gene control.

Syros Website Screenshot

To learn more insights on this intriguing topic, subscribers can log-in or you can purchase access to BSB Premium Content. 

This content is restricted to subscribers

Super Enhancers – what are they and why do they matter in cancer research?

Sometimes you get lucky before a conference and catch an interview with a thought leader ahead of time when it’s more relaxed and less fraught with all the demands of meetings etc while there.

rick young

Dr R Young, Source: WI

That good fortune happened to me on the Friday before the recent AACR conference in San Diego, when I recorded an interview with Dr Richard Young, (Whitehead Institute & MIT and scientific co-founder of Syros), who was giving a plenary talk on the Sunday at AACR entitled, “Transcriptional and Epigenetic Control of Tumor Cells.”

Epigenetics and transcriptional changes are fascinating concepts to me because they get right to the heart of what’s going on deep in the oncogenes and how they control processes in cancer. Clearly, in simplistic terms, if we can understand how things change and evolve, then we can potentially devise better strategies to overcome them. Instead of targeting a protein kinase with a small molecule or a cell surface antigen with a monocloncal antibody, this is an altogether different approach. Protein-protein interactions such as MYC, RUNX1, p53/TP53 etc have long been the bugbear and frustration of many good researchers, precisely because they are challenging to target with conventional approaches.

So what’s new and why am I really excited about these new developments?

Subscribers can log-in to read our latest insights or you can purchase access to BSB Premium Content. 

This content is restricted to subscribers

error: Content is protected !!