Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘cancer’

International Society of GastroIntestinal Oncology (ISGIO) meeting

By on September 22, 2010

IMG_0130It’s been quite a busy week with new projects, proposals and contracts on the go plus we’re heading off to the International Society of GastroIntestinal Oncology (ISGIO) meeting in Philadelphia tomorrow.

Jaffer Ajani does a really nice job of organising this educational conference. It includes the latest updates in the field from a esteemed panel of experts, as well as practical case studies, to help teach a diverse international and US audience how to manage complex or unusual cases.

There’s not a lot of science, but there is serious emphasis is on practical learning and questions from the attendees are encouraged, which I really like. They also have proffered papers on clinical issues, which encourages young up and coming clinicians or researchers to present their work and gain some feedback.

The thought leaders are generally relaxed, approachable and chatty during the breaks, so this makes networking much more fun. John Marshall from DC, for example, is nearly always guaranteed to make the audience (and sometimes his fellow panel members) sit up and pay attention by asking provocative questions or creating a controversy to challenge people’s thinking. A good debate usually follows as a result.

If anyone is going to the meeting or is in Philly and wants to meet up, do let me know and schedule permitting, I do try to accomodate requests. My email link is in the right margin and the phone link in the About page under the blog header – just click on the Google Voice widget to leave a message.

Finally, I would really like to thank all the readers who share papers, suggest topics either in person at conferences or by email or through their thoughts and observations as a result of interacting with this blog. It is much appreciated and I learn from others too. Science, cancer research, drug development and commercialisation were not meant for lonely activity by the nudist on the late shift, but as an interactive learning environment where we can all benefit. That’s what makes it all much more fun.

Please keep the correspondence and suggestions for new blog topics coming. I may not get round to them all in the week they are sent, but do try to research and schedule them at some point.

PIK3CA, MEK and mutant KRAS in cancer

By on September 10, 2010

One of the current challenges with developing new targeted agents in oncology is the tendency to rush various agents, whether monoclonal antibodies (mAB) or tyrosine kinase inhibitors (TKIs) into the clinic before we know how they might best work or in what potential combinations based on the precise underlying biology.

Another challenge I see is old school chemotherapy approaches permeating new development thinking. By this, I mean the traditional concept of testing therapies in advanced, metastatic and highly refractory disease where the tumour burden is high and the chances of getting a decent response is low.

This is one reason I love the I-SPY neoadjuvant concept in breast cancer. Testing a range of compounds prior to surgery based on the potential drivers of the cancer will let us know very early which agents are working or not and which could potentially be selected for subsequent adjuvant treatment after surgery.

Background

Recently, I reading a couple of papers (see references below) on phase I and II trials with a MEK inhibitor (PD-0325901), but it was a little bit with a sinking feeling because the trial design was rather old fashioned and traditional, ie take a bunch of solid tumours in phase I, see what (mixed) signals you get:

"PD-0325901 showed preliminary clinical activity. The maximum tolerated dose, based on first cycle dose-limiting toxicities, was 15 mg BID continuously. However, 10 and 15 mg BID continuous dosing and 10 mg BID 5 days on/2 days off schedules were associated with delayed development of RVO; thus, further enrollment to this trial was stopped."

Where RVO was retinal vein occlusion.

Next, do a phase II in a big (ie large potential patient numbers), advanced, metastatic and highly refractory cancer.  Predictably, the results were unsurprising:

"PD-0325901 did not meet its primary efficacy end point."

If we looked at those results in isolation, we might be tempted to dismiss the idea that the MEK inhibitor doesn't work and abandon it.

A different way of thinking

That said, I was much more encouraged by another article from another group that looked at the problem completely differently with exactly the same MEK agent.  If you think about it, a focused sniper rifle strategy is often going to be more effective than a bludgeoning blunderbuss.

They looked at the basic evidence that:

"Mutational activation of PIK3CA, which commonly co-occurs with KRAS mutation, provides resistance to MEK inhibition through reactivation of AKT signaling"

And then set out to look at this relationship more clearly in animal models:

"to determine the MEK dependence of tumors with mutational activation of the pathway. These studies indicate that many KRAS mutant tumor cell lines are, contrary to the prevailing view, sensitive to the MEK inhibitor PD0325901, and hence, dependent on the RAF/MEK/ERK signaling arm.

Resistance to MEK inhibitors in the relevant cell lines is not an intrinsic feature of KRAS oncogenic function but instead mutational activation of PIK3CA is present in most, but not all, MEK resistant KRAS mutant cancers."

It's hard to argue with that logical approach.

Findings

The article is well worth reading and nicely put together, but here are the main findings of the research:

  1. A subset of KRAS mutant cells depends on MEK/ERK signaling
  2. Coexistent KRAS and PIK3CA mutations prevent cyclin D degradation and sensitivity to MEK inhibition
  3. Selective knockout of mutant PIK3CA allele confers MEK/ERK dependence
  4. Sustained cyclin D expression and bypass of MEK inhibitor–induced G1 arrest correlates with MEK antagonist efficacy
  5. Combined inhibition of both MEK/ERK and PI3K/AKT pathways suppresses the growth of tumors with coexisting KRAS and PIK3CA mutations

 

Implications for the future

The thoughtful approach behind Halilovic et al's data is particularly interesting:

"Mutational activation of KRAS is a common event in human tumors. Identification of the key signaling pathways downstream of mutant KRAS is essential for our understanding of how to pharmacologically target these cancers in patients.

We show that PD0325901, a small-molecule MEK inhibitor, decreases MEK/ERK pathway signaling and destabilizes cyclin D1, resulting in significant anticancer activity in a subset of KRAS mutant tumors in vitro and in vivo."

KRAS mutant tumours are particularly relevant to colorectal cancer.  Recently, we have seen that patients with colorectal cancer who have wild type, but not mutant, KRAS are more much more likely to respond to treatment with EGFR therapy ie Erbitux and Vectibix, allowing for careful patient selection and exposure.

What about melanoma where mutant RAS may stop the activity of RAS inhibitor such as PLX4032? Could adding a MEK inhibitor help overcome the problem in some cases, or perhaps that would be too simple? We don't know, but I'd love to see some research data in appropriate xenograft models in this area.

The problem is that there is currently no therapeutic agent that directly inhibits KRAS function, so the Halilovi data have very important implications for tumours driven by mutant RAS.

What the new data tells us:

"These data suggest that tumors with both KRAS and phosphoinositide 3-kinase mutations are unlikely to respond to the inhibition of the MEK pathway alone but will require effective inhibition of both MEK and phosphoinositide 3-kinase/AKT pathway signaling."

Bingo!  Now that's a much more elegant approach to defining which patient populations are most likely to respond based on preclinical research before attempting clinical trials and randomly exposing patients who had no hope of responding to the systemic side effects of a treatment.  

Personally, I would dearly love to see more clinical trial selection based on logical, well researched preclinical data rather than a scattergun let's hope and see approach.

We need to get smarter and faster at well designed research that points us in the right direction to increase the chances of better success and improved outcomes.  It will also conserve precious R&D dollars and focus it where it's needed most.

 

References

ResearchBlogging.org Halilovic, E., She, Q., Ye, Q., Pagliarini, R., Sellers, W., Solit, D., & Rosen, N. (2010). PIK3CA Mutation Uncouples Tumor Growth and Cyclin D1 Regulation from MEK/ERK and Mutant KRAS Signaling Cancer Research, 70 (17), 6804-6814 DOI: 10.1158/0008-5472.CAN-10-0409

Haura, E., Ricart, A., Larson, T., Stella, P., Bazhenova, L., Miller, V., Cohen, R., Eisenberg, P., Selaru, P., Wilner, K., & Gadgeel, S. (2010). A Phase II Study of PD-0325901, an Oral MEK Inhibitor, in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer Clinical Cancer Research, 16 (8), 2450-2457 DOI: 10.1158/1078-0432.CCR-09-1920

LoRusso, P., Krishnamurthi, S., Rinehart, J., Nabell, L., Malburg, L., Chapman, P., DePrimo, S., Bentivegna, S., Wilner, K., Tan, W., & Ricart, A. (2010). Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral MAPK/ERK Kinase Inhibitor PD-0325901 in Patients with Advanced Cancers Clinical Cancer Research, 16 (6), 1924-1937 DOI: 10.1158/1078-0432.CCR-09-1883

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Selective cell death mediated by small conditional RNAs

By on September 9, 2010

Cancer cells are characterized by genetic mutations that deregulate cell proliferation and suppress cell death. To arrest the uncontrolled replication of malignant cells, conventional chemotherapies systemically disrupt cell division, causing diverse and often severe side effects as a result of collateral damage to normal cells. Seeking to address this shortcoming, we pursue therapeutic regulation that is conditional, activating selectively in cancer cells.

via www.pnas.org

This was an interesting paper that caught my eye in PNAS last night.  Further reading demonstrated that the process uses small RNA molecules. The idea behind this approach was that the small RNA molecules can be programmed to attack only specific cancer cells; then, by changing shape, those molecules cause the cancer cells to self-destruct.

Normal cells die after a period of time and are replaced by new ones, a process called programmed cell death or apoptosis.  In a tumour, the cells continue to proliferate and form a mass, growing new blood vessels to feed the structure via angiogenesis.  

One of the things that has absorbed researchers for years is how to stop that process and induce cell death in cancer cells without killing a lot of normal cells at the same time.  To do this, we need to find ways of distinguishing cancerous from normal cells, thereby inducing a more targeted and selective approach to destruction and reducing unwanted side effects.  ]

This is not as easy as it sounds though!

In the PNAS study, the researchers took small conditional RNAs, which are less than 30 base pairs in length and are hairpin shaped molecules as shown in the photo below.

Picture 7

The press release from Caltech described the concept as thus:

"The researchers' method involves the use of two different varieties of small conditional RNA. One is designed to be complementary to, and thus to bind to, an RNA sequence unique to a particular cancer cell—say, the cells of a glioblastoma, an aggressive brain tumor.

In order to bind to that cancer mutation, the RNA hairpin must open—changing the molecule from one form into another—which, in turn, exposes a sequence that can spontaneously bind to the second type of RNA hairpin. The opening of the second hairpin then reveals a sequence that binds to the first type of hairpin, and so on. 

In this way, detection of the RNA cancer marker triggers the self-assembly of a long double-stranded RNA polymer."

Essentially, this is a clever way to use small conditional RNAs to the trick cancer cells into self-destructing by selectively forming long double-stranded RNA polymers that mimic viral RNA.

The researchers tested the RNA concept in the lab in xenograft models derived from three types of cancers: glioblastoma, prostate carcinoma, and Ewing's sarcoma so far, with some success:

"The molecules caused a 20- to 100-fold drop in the numbers of cancer cells containing the targeted RNA cancer markers, but no measurable reduction in cells lacking the markers."

Now clearly this approach has a long way to go before we see it in clinical trials, but there's nothing like starting off your day with exciting new technology approaches that may have application in the near future.

We need more creative research like this in oncology!

 

Photo Credit: Caltech

 

ResearchBlogging.org Venkataraman, S., Dirks, R., Ueda, C., & Pierce, N. (2010). Selective cell death mediated by small conditional RNAs Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1006377107

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LKB1 is a master kinase in cancer

By on September 1, 2010

"LKB1 is a master kinase"

What a great subheader in a paper last year by Reuben Shaw (journal link below).

Liver kinase B1 (LKB1) first got my attention at the AACR lung cancer meeting in San Diego earlier this year, when a couple of translational researchers mentioned it during informal discussions about how it might play a critical but subtle role in lung cancer and potentially other cancers.

Looking at the literature, LKB1 was first identified as a tumor suppressor gene on human chromosome 19p13, responsible for the inherited cancer disorder Peutz-Jeghers Syndrome (PJS).  However, the interest at the AACR meeting centred around it being one of the most commonly mutated genes in sporadic human lung cancer, including some subtypes of non-small cell lung carcinoma (NSCLC).

Of course, being very interested in potential druggable targets, I was trying to get my head around this particular kinase.  Several scientists and researchers explained to me patiently that LKB1 is involved in energy levels and metabolism, rather than cell signalling per se, so it kind of went by the wayside as other interesting targets came up lately, associated with small molecule tyrosine kinase inhibitors (TKIs) or monoclonal antibodies.

Still, the fact that LKB1 and AMPK control cell growth in response to environmental nutrient changes stuck in the back of my mind while I quietly wondered whether it would eventually have it's day.

Fast forward to an AACR press conference this morning about the role of metformin, a biguanide therapy for managing hyperglycemia and diabetes, in the role of chemoprevention.  I'm going to write more about that meaty topic in another more detailed post tomorrow, but what fasinated me was the mention by Dr Michael Pollak about metformin altering cell energy levels, ie a control system that senses cell energy supplies and low reserves.  

It was also mentioned that the activation of the LKB1-AMPK pathway downregulates gluconeogenesis.  This process represents the export of energy from hepatocytes to the organism in the form of glucose.  In turn, this reduces blood glucose concentration, which results in a secondary decrease in insulin level.  

Essentially, the inhibition of hepatic gluconeogenesis is now felt to be a key process underlying the utility of biguanides in the therapy of type II diabetes.

What is interesting on several levels is:

  • Studies showing raised levels of free or circulating IGF1 may be associated with an increased risk of developing cancer
  • Epidemiology studies amongst people with diabetes taking metformin who may have a lower risk of developing cancer

Of course, when we look at the broader picture, we can see the interactions across several pathways, which makes the whole situation highly complex:

Picture 9
Source: University of Dundee

Clearly, there is now enough evidence to warrant researching the effects of metformin in cancer prevention, especially given that it is orally available, has had no long term safety issues and is now generically available.  These factors, coupled with a greater understanding of the biology of the involved pathways may make a productive new area of cancer research.

Tomorrow, I will cover the latest research involving metformin for chemoprevention in colorectal and lung cancers in more detail.

 

ResearchBlogging.org Shaw RJ (2009). LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta physiologica (Oxford, England), 196 (1), 65-80 PMID: 19245654

Shackelford DB, & Shaw RJ (2009). The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nature reviews. Cancer, 9 (8), 563-75 PMID: 19629071

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Is the cancer research paradigm changing?

By on August 18, 2010

Over the weekend, a reader (a scientist in translational medicine) kindly sent me the link to a paper on PARP inhibition and asked:

"Is this a sign of the new wave of oncology drug development? Rather than basing treatment on cancer tissue type (eg. breast, prostate, colorectal), the underlying genetic mutation regardless of tissue of origin will be used for targeted agents. Imagine a randomized Ph2 trial of all BRCA1/2 deficient patients vs. non-mutated patients. Of course, this same rationale would have not worked for K-ras mutation patients with EGFR inhibitors in NSLCLC vs. Colorectal."

My short answer is basically, yes.

It may, however, take a while for this to evolve fully clinically, but you can already see the movement starting at AACR meetings, where they organise topics around pathways.

Unfortunately, at ASCO and ASH things are still discussed in cancer specific sessions, which I increasingly find more difficult to follow and plan for.  For example, suppose I'm interested in pipeline PI3-kinase inhibitors.  There might be something at 8.45am in North Hall A on one tumour type, but another at 9.00am on the other side of the convention centre in Room 330A in the East Building on a different cancer.  Ugh, no wonder we all joke about the #blisterwalks and increasingly lack of time for networking at conferences – we're all too busy dashing between sessions in highly frazzled, rather than leisurely fashion!

I do believe the translational medicine and scientists are right in the pathway over tumour approach though and have been advocating for a pathway driven approach for some time on this blog.  If you haven't read it yet, the short four part series on pathways and treatment in lung cancer earlier this year may be useful (see posts here, here, here and here) for examples of how lung cancer specialists (translational scientists and clinicians together) are leading the way in pioneering this concept.

In the example my correspondent gave, PARP inhibitors are being tested in BRCA1 and 2 positive tumours for olaparib (AstraZeneca), i.e. breast and ovarian cancers, whereas looking at the clinical trials database, Sanofi-Aventis are taking a more traditional approach with iniparib (BSI-201) and looking at different tumour types without the BRCA mutation.

Meanwhile, Abbott are also taking a very creative approach with their PARPi, veliparib (ABT-888), by not only looking at BRCA-positive cancers but also getting involved in the I-SPY2 neoadjuvant trial in breast cancer, which was a very smart move in my opinion.  You can read more about the agents in that groundbreaking study protocol from the interview with Dr Sue Desmond-Hellmann.  It's a great example of seeking to treat women diagnosed with early breast cancer with different therapies based on their underlying biology of their tumour, thereby enabling us to see what works and what doesn't earlier than we would normally.

It's going to be interesting to see how all these different R&D strategies work out commercially.  For the record, I think olaparib may well be the first targeted agent to show benefit in patients with cancers that result from BRCA1 or BRCA2 gene mutations.  That's quite exciting in itself, and hopefully, AZ have also learned considerably from the mistakes made with gefitinib (Iressa).  Whether the specific targeted and scientific approach will win over a more commercial strategy, we'll have to wait and see.

The advantage of a specific targeted strategy is that if you get the biomarker right, the people who are most likely to respond to a therapy will more likely receive it plus the response rates and outcomes, in theory, should be better.  Those who are less likely to respond are spared of the systemic exposure and false hope.

Some marketers will also argue that it may also, however, limit your market commercially, but my argument is that a highly targeted agent will actually get more prescriptions in the long run because it will be easier for an oncologist to choose therapy accordingly and good results reinforce usage and loyalty. Standing out from the crowd with superior efficacy in a well defined population is a much more elegant approach to this marketer 🙂

In a catch-all strategy, you may believe that by targeting a bigger market you will win more commercially, but the risk is that the response rates will be lower in a heterogeneous population (the wins and losses will cancel out to some extent). Thus if a competitors more targeted approach actually works, they win and you have no biomarker to answer with to allow oncologists to choose between the agents. Increasingly, they are reluctant to treat everyone willy nilly because of high costs, whether in terms of patient co-pays for oral therapies or more draconian restrictions for iv therapies from insurers.

Developing targeted agents is very different from traditional chemotherapy. Oncologists now want to know who is most likely to respond to a given therapy and treat those subsets accordingly rather than randomly treat and expose everyone to not insignificant systemic side effects of therapy.  One of the best concepts we have right now is to have multi-functional research and clinical practice that marries identifying the key pathways and mutations with targeted therapies designed to knock out or shutdown the aberrant cell signalling.

We have a ways to go, but the tide is already turning.

 

ResearchBlogging.org Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, & Carmichael J (2010). Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet, 376 (9737), 235-44 PMID: 20609467

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Fall cancer conference schedule

By on August 9, 2010

The dog days of summer are now here and looking ahead at my conference schedule over the next couple of months, things look quite busy already.

Here's a list of some of the meetings and events I plan to attend based on my public Plancast schedule:

Whew!

Come December there will also be ASH in Orlando and the San Antonio Breast Cancer Symposium back to back, so a busy season ahead awaits already.

If you would like to meet up at any of the meetings for coffee, a chat or networking, please let me know.  You can email me here or comment below.

 

Somatic mutations and pathway alterations in cancer

By on August 5, 2010

"The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics."

So began today's journal article from a letter to Nature (link below) from scientists at Genentech.  They went on to state that they have looked at:

"The identification of 2,576 somatic mutations across 1,800 megabases of DNA representing 1,507 coding genes from 441 tumours comprising breast, lung, ovarian and prostate cancer types and subtypes. We found that mutation rates and the sets of mutated genes varied substantially across tumour types and subtypes.

Statistical analysis identified 77 significantly mutated genes including protein kinases, G-protein-coupled receptors such as GRM8, BAI3, AGTRL1 (also called APLNR) and LPHN3, and other druggable targets.

Integrated analysis of somatic mutations and copy number alterations identified another 35 significantly altered genes including GNAS, indicating an expanded role for Ga subunits in multiple cancer types."

The goal of this type of analysis is to look for patterns and alterations associated with disease and try to figure out which are potentially druggable targets for drug development.  The researchers went on to note:

"Our study represents a substantial expansion of the knowledge base of cancer somatic mutations. Of the 845 genes with proteinaltering mutations identified in this study, 361 (43%), including 13 significantly mutated genes like TLR4, SPOP and NRG3, have not previously been reported."

image from www.flickr.com That's great news. Of course, it should be noticed that theory is one thing, but until a pipeline compound enters into clinical trials and we see the results of extensive studies, we won't know whether the target is truly a relevant one in human cancers or not.

Not all mutations may occur in every person though, as we have seen in lung cancer where some people might have an EGFR mutation, some an ALK mutation and so on. The secret to this approach is to start documenting the likely targets and go looking to see how many exist, which ones might be a critical driver and which ones are merely passengers.

Clearly though, it does help to have an idea of what the needles in the haystack might look light before going hunting for them to increase the chances of success.

Photo Credit: Yellow Book

 

ResearchBlogging.orgKan, Z., Jaiswal, B., Stinson, J., Janakiraman, V., Bhatt, D., Stern, H., Yue, P., Haverty, P., Bourgon, R., Zheng, J., Moorhead, M., Chaudhuri, S., Tomsho, L., Peters, B., Pujara, K., Cordes, S., Davis, D., Carlton, V., Yuan, W., Li, L., Wang, W., Eigenbrot, C., Kaminker, J., Eberhard, D., Waring, P., Schuster, S., Modrusan, Z., Zhang, Z., Stokoe, D., de Sauvage, F., Faham, M., & Seshagiri, S. (2010). Diverse somatic mutation patterns and pathway alterations in human cancers Nature DOI: 10.1038/nature09208

Hedgehog (Hh) signaling in cancer: a new pipeline emerges

By on August 4, 2010

The other day I came across an interesting journal article on Hedgehog signalling, how it might be implicated in some cancers, and the potential issues associated with targeting the pathway:

“… several issues surrounding the basic biology of the Hh pathway in human cancers remain unclear. These include the influence of specific oncogenic events on Hh signal transduction, the precise mode of Hh signaling (i.e., autocrine or paracrine) that occurs within human tumors, and the best means to inhibit aberrant pathway activity in the clinical setting.

The cancer stem cell (CSC) hypothesis may explain a number of clinical phenomena, such as unchecked self-renewal and the development of metastatic disease, and to some extent, the Hh signaling pathway has been implicated in all of these processes.

Therefore, Hh pathway inhibitors may also represent some of the first agents to formally examine the CSC hypothesis in the clinical setting.”

3657524851_b1936f3830_mWe’ve covered a little about the basics on Hedgehog and Smoothened in the past on this blog (see here and here for examples), but the latest journal article covers some new topics of discussion. In particular, I loved Fig 4 but cannot reproduce it here for copyright reasons, but you can check it out through the Research Blogging for peer reviewed science articles link below.

In the past, it was thought that Hedgehog signalling was associated with basal cell carcinoma and medulloblastoma, both fairly rare cancers.

The new review provides some useful references for involvement in other cancers including:

  • Multiple myeloma
  • Pancreatic
  • Ewings sarcoma
  • Melanoma
  • Breast cancer
  • Ovarian cancer
  • Prostate cancer

And a few others as well.  Of course, it is still unclear whether Hedgehog is a critical driving aberration in these tumours, but as early clinical trials expand into new indications with pipeline drugs, so we will learn more.  It is possible that multiple combinations with a cocktail of therapies each aimed at different targets may be the way to go, but most likely an incremental and conservative approach will be reflective of the initial offerings.

In terms of agents targeting Hedgehog, a number of companies are active in this space:

  • Roche Genentech/Curis have GDC-0449, a small molecule inhibitor.
  • Curis have Debio-0932, a heat shock protein inhibitor, which they are developing with Debiopharm.
  • Another Hsp90 inhibitor that is in very early development for solid tumours and pancreatic cancer is IPI-926 from Infinity.
  • Novartis have LDE225, which targets Hedgehog and Smoothened.
  • Exelixis/BMS are testing XL139, which also targets Smoothened, in gastric and small cell lung cancers and multiple myeloma.

There are probably a few others, both those are the ones that jumped to mind just now.  If you know of any I’ve missed, please do add them in the comments section below.

The Pharma pipeline in this field is obviously burgeoning, but most are in fairly early trials having not long moved out of preclinical, so it will be a while before we know whether this is a useful target for therapeutic intervention or not.

 

Photo Credit: Dave-F

ResearchBlogging.orgMerchant, A., & Matsui, W. (2010). Targeting Hedgehog — a Cancer Stem Cell Pathway Clinical Cancer Research, 16 (12), 3130-3140 DOI: 10.1158/1078-0432.CCR-09-2846

 

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The ravages of smoking and cancer…

By on July 26, 2010

We all know that long term exposure to chemical insults and carcinogens from smoking and alcohol can act as irritants, leading to biochemical changes that can induce the development of hyperplasia, and potentially, carcinomas.

Over the weekend I was shocked to learn that Alex "Hurricane" Higgins, former World Snooker Champion, had passed away aged 61 from throat cancer.  He was an incredible talent who will be sadly missed and remembered for many years to come.

I wrote a bit more about it here: be warned though, the before and after photos are rather distressing 🙁

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