Message from the coordinator


Dear LKI member, 

The summer season is fast approaching. ASCO is behind us.... Time for reflection. Reflection on the remarkable progress being made on several fronts, but also reflection on cancers where progress is lacking. Also within the LKI, we should remain aware of all the challenges and opportunities posed by modern cancer research. More than ever, research is multidisciplinary, and if we are to make good progress in translating basic research findings into cures or diagnostics for patients, then we must ensure that all relevant partners find each other regularly in a common forum. That is exactly why LKI is facilitating the set up of novel focus groups, where partners from the entire research chain (ranging from basic over translational to clinical cancer research) can meet each other, discuss problems, generate common ideas, make plans for common projects and grant proposals etc etc.
We are already looking forward to the upcoming academic year, but in the meantime we wish you all the best for a refreshing and revitalising summer season.

Yours sincerely, 


 

Prof Dr Jo Van Lint
Coordinator Translational Cancer Research
& Editor LKI News
Prof. Dr. Johan Swinnen
Chairman
Taskforce Cancer Research
In the spotlight


Single cell analysis platform in the Thierry Voet lab will revolutionise studies on cancer evolution and heterogeneity.
Tumors develop various subpopulations of cancer cells. The extent, nature and biology of this cancer cell diversity remains largely unknown. This also impairs the development of novel effective therapies. With 1.7M € support of the Stichting tegen Kanker, the team of Thierry Voet is currently setting up a platform that can be used for the fast and very detailed analysis of a large number of individual cancer cells in a sample. This analysis system consists of various components, including (i) a droplet-fluidics platform that allows analysis of thens of thousands of individual cells via gene expression analysis by RNA sequencing (ii) a cell sorter for the analysis of individual cells, which in combination with high throughput pipetting robots allows for an integrated analysis of DNA and RNA of the same cell, (iii) an apparatus for the isolation of very rare cells (e.g. tumor cells circulating in the bloodstream of a patient) as well as an apparatus for the detection of very rare mutations. 
Together with sequencing and bioinformatics infrastructure, this platform will allow the investigation of cellular heterogeneity of tumors at an unprecedented level. This platform will certainly deliver novel insights into the biology of cancer evolution (and progression). 

The CRISPR Platform in the Adrian Liston lab: a novel tool for functional genomics and target identification
The Liston lab has set up a CRISPR-based genome editing plaform (headed by Dr Susan Schlenner). This platform will undoubtedly become a big asset for the study of cancer gene function and for unraveling the effect of specific cancer gene mutations (e.g. via the establishment of mouse models harboring particular cancer mutations). 
The platform offers the following possibilities: 
- in silico design of mutant alleles
- vector cloning support
- design and testing of CRISPR constructs
- all-in-one plasmids (GFP/RFP) are used for CRISPR SpCas9/SpCas9HF/CasN/hSaCas9/Cpf1 (offering the advantage that different PAM sites provide a broader choice to place a CRISPR)
- human/mouse cell line mutagenesis
- any cell population/line that can be expanded can be used
- single cells are sorted for clonality
- murine C57Bl/6 ES cell mutagenesis (JM8.A3 ES cells) for the generation of mouse models
It is possible to create knock-out alleles, knock-in alleles and conditional alleles. Future plans of the platform are zygote/pronuclear injection (for knock-out as well as knock-in alleles) and CRISPR screening (e.g. for drug development). The platform will collaborate closely with InfraMouse (Dr Enrico Radaelli).

MoSAIC installs PET/MRI scanner for preclinical research: a new era for the study of your mouse cancer models
The "beast" being hauled into the MoSAIC labs The Bruker Biospec safe and well in place, being prepared for full operation by Oct/Nov 2016

The Molecular Small Animal Imaging Center (MoSAIC) at KU Leuven has received funding for the installation of a Positron Emission Tomography (PET)-Magnetic Resonance Imaging (MRI) scanner for preclinical research. The new instrument will allow for the simultaneous acquisition of PET and MR images by integrating a PET insert into a 30cm bore 7 Tesla MRI scanner. The system will be one of the first worldwide, combining Bruker Biospins large bore Biospec MR scanner with Bruker’s Albira PET hardware. This will not only improve MoSAIC’s capacity for preclinical research in oncology but provides also simultaneous information of dynamic processes like tissue perfusion, metabolism, drug distribution, tissue oxygenation and many more. The new instrumentation will be complementary to the recently installed clinical PET-MRI at UZ Leuven. Funding for the preclinical PET-MRI was provided by the Hercules stichting (7T MRI, promotor Prof. U. Himmelreich) and the stichting tegen kanker (PET insert, promotor Prof. C. Deroose). Installation has recently commenced. It is expected that the system will be fully operationable by October/ November 2016.

Oncoforum 2016 - still going strong after 13 editions
Scientists are not superstitious. At least, so they say... This year we had Oncoforum nr 13. A bad omen? Definitely not. Or maybe yes? Well, except for one last minute cancellation (of Prof. Charlie Swanton), we can certainly say that this year's Oncoforum was a great success. And this for several reasons.
1) because of the truly inspiring talks of the 3 invited keynote speakers: Louis Staudt (NCI, Bethesda) on lymphoma therapy inspired by structural and functional genomics, Carmen Garrido (Université de Bourgogne) on the remarkable role of heat shock proteins in cancer, and Charlotte Ng (University Hospital Basel, bravely replacing Charlie Swanton on only 3 days notice!) on cancer evolution and heterogeneity.
2) because the 2-minute poster blitz presentations gave a kaleidoscopic view of the truly amazingly varied range of cancer research(ers) that we are blessed with in the LKI. A fact that caught the attention of the invited keynote speakers.
3) because of the tech talks that focused on three of the many technical resources available at the LKI. Bart Ghesquière (VRC Research Center, Leuven) quite rightly pointed out the (often forgotten) fact that metabolism is the process that is most closely related to the ultimate phenotype of a cell, and so he presented an overview of the varies ways in which isotopes can be used in mass spec for following the activity of various metabolic pathways. Nadine Ectors (UZ Leuven BioBank) gave an overview of the possibilities (and regulatory aspects) for the use of human body material (clinicians at UZ Leuven are collecting a wealth of tissue material, available for sharing with basic scientists). And Susan Schlenner (Liston Lab) gave an overview of the CRISPR-based genome editing platform, for which we're sure any team can dream up many applications targeting their favorite gene in their favorite mouse model system.

Prof. Louis Staudt (NCI) in a gentle pre-talk chat with Prof. Ignace Vergote (chairman LKI) Prof. Carmen Garrido (Université de Bourgogne) on the wonders of Hsp70 and 90 Prof. Charlotte Ng (University Hospital Basel)
our heroine of the day!
The Oncoforum posters were very well visited:
always a good sign for a meeting!
Dr Adriaan Vanderstichele, preaching the joys of homologous recombination deficiency research  Prof. Jo Van Lint (L) and Prof. Daan Dierickx (R), quietly contemplating some inspiring lectures 


4) because of some precious jewels that came up in the guise of the selected poster talks in all three key fields: basic, translational and clinical research. Roberto Vendramin (of Chris Marine's lab, VIB-CME) presented a wonderful story on Melanoma addiction to the LncRNA SAMMSON. Kevin Hollevoet presented a highly original way to deliver therapeutic antibodies via intramuscular gene transfer. And in the clinical category, Iris Elens (Child Psychiatry, UZ Leuven) reminded us that not only do we need to take care of patients while they're ill, but we also need to remain aware of what's happening after the (often quite toxic) treatment phase. This was nicely illustrated by her study of cerebrospinal fluid toxicity markers during treatment, which she found to correlate with cognitive performance in adult childhood leukemia survivors.
Awards given: the award for best abstract went to Dr Kevin Hollevoet for his work on gene transfer for delivery of therapeutic antibodies, the award for best poster went to Michael Olvedy for his work on melanoma tumor suppressor genes. The awards of the public went to Marlies Vanden Bempt for her work on NUP214-ABL1 fusion cooperation with TLX1 in the development of T-cell acute lymphoblastic leukemia, and to Erminia Romano for her work on BNIP3 as a key modulator of the melanoma-macrophage interface
During the closing reception, participants agreed that this was a strong Oncoforum edition, a stimulating one, and a heart warming one. The latter in view of new therapeutic hope created by various ongoing research lines, but also in view of the pride that we can take in what is happening (and what is possible) in our institute.

LKI booth at Knowledge for Growth convention (Ghent) enjoyed overwhelming interest from biotech and pharma.

It is a well known fact that Flanders harbors a thriving biotech and pharma industry sector, in part certainly explained by a feeding layer of excellent academic biomedical research . As a consequence, it is only appropriate that all relevant players in this field should meet annually for an overview of what's going on in this sector. And that's exactly the purpose of Knowledge for Growth, organised by FlandersBio and the largest regional biotech/pharma event in Europe! Over 1300 participants (from 16 different countries) met on May 26th in Ghent for keynote lectures and breakout sessions. The latter on topics such as: meeting unmet clinical needs, drug discovery & diagnostic technologies, partnering opportunities with pharma, Flanders clinical test region, access to finance & funding, etc etc. 
An important ingredient at Knowledge for Growth are the booths of various companies, as well as scientific institutions. Together these booths literally constitute a kind of forum that is intensively visited by all participants for informal discussions between potential partners . Besides pharma and biotech companies, also VITO, VIB, UGent LifeTec, Imec etc etc exhibited their organisation via a booth. This year, the LKI was present for the first time. We set up our booth with eager anticipation, not knowing exactly what to expect from a meeting so different from classical scientific meetings. The 7 posters of our booth focused on: presentation of the LKI and its objectives, an overview of the broad portfolio of core facilities on which we can rely to support our research, a glimpse at some recent key LKI papers in the fields of basic, translational and clinical cancer research, and a large organigram showing all LKI research teams together with their research lines explained in a nutshell. 
To our pleasant surprise, the interest in our LKI booth was overwhelming. Visitors were clearly impressed by what the LKI has in store along the entire line of basic, translational and clinical research. 

Levensloop (Relay for Life) 2016: LKI scientists join patients and relatives in a relay run festival in support of the Stichting tegen Kanker. 
The Leuven Cancer Institute and the departments of Oncology and Human Genetics have this year joined forces and participated in the Relay for Life on 23 and 24 April in support of the Stichting tegen Kanker. (Cancer Research Foundation) For 24 hours, our 76 person strong team ran laps and walked the grounds of the army barracks in Heverlee. By doing so, they have shown their support for the "fighters", (ex-)cancer patients, in their round the clock struggle. There were performances, good food and drink, games for kids ... The at times very bad weather was the only factor that made it sometimes difficult to make a real family outing of it!
In total, this event has gathered € 191,982. We can be justly proud that the Leuven Cancer Researchers team contributed € 5,649 to this sum!
Prizes, grant awards & honours


Abhishek Garg wins the prize of the KU Leuven Research Council, category Biomedical Sciences

The award was presented to Dr Garg (from the Cell Death Research & Therapy Lab of Prof. Patrizia Agostinis) for his groundbreaking work on damage-associated molecular patterns and immunogenic cancer cell death in cancer immunotherapy. Here is a summary of this fascinating work, by Abhishek himself:

Cancer is occurring like an “epidemic disease” and failure of our immune system in controlling cancer complicates therapeutic efforts. Nurturing a dysfunctional immune response is in fact a cardinal hallmark of cancer. Owing to this, an anticancer therapy that simultaneously kills cancer cells and activates immunity is considered a “holy-grail” in the field of oncology. Over last several years, research from other as well as our lab has found that certain anticancer therapies are able to induce a peculiar form of cancer cell death (so-called immunogenic cell death or ICD) that associates with increased exposure of “danger signals” [1]. Under normal conditions, these danger signals are kept in an “inactivated state” by the cancer cells; however upon ICD they get liberated thereby alerting the immune system about the dangerousness of cancer cells. The immune system thereafter uses the “trail” of danger signals being released from dying cells to track and recognise them, a process that eventually paves way for direct immune-mediated elimination of residual live cancer cells, causing tumour-rejection. Our original research has led to important discoveries relevant for immunology of cancer cell death and ICD as well as their therapeutic application in cancer therapy. Firstly, we characterized the most powerful form of ICD reported thus-far (induced by hypericin-based photodynamic therapy) that exposes danger signals at faster pace and at higher amounts than chemotherapy; and eventually engages a strong dying cells-immune cells interface [2-4]. Next, we translated these findings towards preclinical settings by creating novel, next-generation anticancer vaccines against the highly aggressive brain cancer, glioblastoma [5]. These next-generation vaccines induced highly effective anti-glioblastoma immunity, especially in combination with chemotherapy in a clinically-relevant set-up [5]. In fact, a peculiar immunological-signature generated by these vaccines, when correlatively analysed in human patients of glioblastoma, was found to associate with significantly prolonged survival of these patients [5]. These latter results outlined the importance of robust biomarkers that can predict increased/decreased patient survival and assist in clinical patient management/decision making. Thus we used ICD to retrospectively analyse data of >4000 cancer patients (with lung, breast or ovarian malignancies) and delineated robust ICD-derived biomarkers that can categorise patients into low risk (likely to survive longer) or high risk (likely to survive relatively less) immunological-groups [6]. These observations exposed the dire need to delineate in high-risk cancer patients, mechanisms that could be “de-railing” anti-cancer immunity. To this end, we delineated several mechanisms that can lead to immunotherapy resistance e.g. catabolic suppression of danger signals (via autophagy, a self-degradative process) [7, 8], inactivation of stress responses or signalling pathways that can help in trafficking of danger signals [9] and last but not least, the ability of certain cancer cells to avoid being “eaten” by immune cells thereby inhibiting the proper processing of cancer cells for immune-activation [10]. In fact, we found the latter mechanism to be operating in various cancer patients such that this resistance mechanism predicted patient positive responses to ICD-inducing therapies [10]. These discoveries made in our lab have helped in advancement of the fields of ICD, danger signals and immunotherapy based on dying cancer cells.
Major papers from our lab on this subject:
1. Garg AD, Galluzzi L, Apetoh L, Baert T, Birge RB, Bravo-San Pedro JM, Breckpot K, Brough D, Chaurio R, Cirone M, Coosemans A, Coulie PG, De Ruysscher D, Dini L, de Witte P, Dudek-Peric AM, et al. Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death. Front Immunol. 2015; 6:588.
2.  Garg AD, Krysko DV, Verfaillie T, Kaczmarek A, Ferreira GB, Marysael T, Rubio N, Firczuk M, Mathieu C, Roebroek AJ, Annaert W, Golab J, de Witte P, Vandenabeele P and Agostinis P. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J. 2012; 31(5):1062-1079.
3.  Garg AD, Krysko DV, Vandenabeele P and Agostinis P. Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin. Cancer Immunol Immunother. 2012; 61(2):215-221.
4.  Garg AD, Krysko DV, Vandenabeele P and Agostinis P. Extracellular ATP and P2X7 receptor exert context-specific immunogenic effects after immunogenic cancer cell death. Cell Death Dis. 2016; 7:e2097.
5.  Garg AD, Vandenberk L, Koks C, Verschuere T, Boon L, Van Gool SW and Agostinis P. Dendritic cell vaccines based on immunogenic cell death elicit danger signals and T cell-driven rejection of high-grade glioma. Sci Transl Med. 2016; 8(328):328ra327.
6.   Garg AD, De Ruysscher D and Agostinis P. Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis. Oncoimmunology. 2016; 5(2):e1069938.
7.  Garg AD, Dudek AM, Ferreira GB, Verfaillie T, Vandenabeele P, Krysko DV, Mathieu C and Agostinis P. ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death. Autophagy. 2013; 9(9):1292-1307.
8.  Garg AD, Dudek AM and Agostinis P. Calreticulin surface exposure is abrogated in cells lacking, chaperone-mediated autophagy-essential gene, LAMP2A. Cell Death Dis. 2013; 4:e826.
9.  Dudek-Peric AM, Ferreira GB, Muchowicz A, Wouters J, Prada N, Martin S, Kiviluoto S, Winiarska M, Boon L, Mathieu C, van den Oord J, Stas M, Gougeon ML, Golab J, Garg AD and Agostinis P. Antitumor immunity triggered by melphalan is potentiated by melanoma cell surface-associated calreticulin. Cancer Res. 2015; 75(8):1603-1614.
10.  Garg AD, Elsen S, Krysko DV, Vandenabeele P, de Witte P and Agostinis P. Resistance to anticancer vaccination effect is controlled by a cancer cell-autonomous phenotype that disrupts immunogenic phagocytic removal. Oncotarget. 2015; 6(29):26841-26860.

William J. Fry Memorial Lecture Award for Prof. Dirk Timmerman
The William J. Fry Memorial Lecture Award was established in 1969 to recognize a current or retired AIUM (American Institute of Ultrasound in Medicine) member who has significantly contributed in his or her particular field to the scientific progress of medical ultrasound. The award is presented this year to Prof Dirk Timmerman, head of gynecological ultrasound at the University Hospitals Leuven. Prof. Timmerman is founder and coordinator of the International Ovarian Tumor Analysis Group (IOTA), whose aims include the development of new algorithms to detect ovarian cancer, as well as optimal care of patients with adnexal tumors. There are currently 40+ centers throughout the world that are part of this collaborative effort, which has the potential to have a very positive impact on many women from all strata and from all geographic locations.
Upcoming events
 

Tumor Immunology & Immunotherapy Symposium (Leuven, 12-14 September 2016)
Who?
The LKI (KU & UZ Leuven), together with the universities of Ghent and Antwerp invite you to a three day symposium on Tumor Immunology & Immunotherapy.
What about? Hear about significant breakthroughs in this field by a very nice line up of key national and international speakers! This three day symposium  will bring you up to date on topics such as tumor antigens, vaccine based immunotherapy, immune checkpoint blockade, tumor targeting antibodies, adoptive T-cell therapy, the role of gut microbiota, inflammation, tumor microenvironment, immune escape...
Why? The meeting aims to bring together basic and clinical researchers from Flanders with top international players in this field, to bring the latest developments and to foster novel collaborations. ‘Meet the expert’-sessions will give researchers and students the opportunity to meet keynote speakers.
Where? Auditorium BMW2, Campus Gasthuisberg, O&N2
When? September 12 (noon) till September 14 (noon)
Look here for the full program and registration

VRC International Metabolism Mini Symposium (Leuven, 6 September 2016)
Who? On behalf of Max Mazzone and Sarah-Maria Fendt, you are kindly invited to the 4th VRC International Metabolism Mini Symposium
What about? This year our mini symposium is focused specifically on immune cell metabolism and we are delighted to announce that the following high profile researchers will speak at our mini symposium:
Susan Kaech (Yale School of Medicine, Yale, USA)
Ajay Chawla (UCSF, San Francisco, USA)
Thorsten Cramer (RWTH University Hospital, Aachen, Germany)
Tiffany Horng (Harvard, Cambridge, USA)
As usual, after the mini symposium, we will organize a possibility for PhD students and postdocs to meet our speakers in one-to-one session. 
When? The symposium will take place on the 6th of September 2016 from 9am to 1pm
Where? Auditorium PSI 91.93 - 110-01 PSI Psychologisch Instituut Tiensestraat 102, 3000 Leuven.
You can find more information on the symposium website
 
SAVE THE DATE: Second scientific speed date (Leuven, 19 October 2016)
The first scientific speed date was a success, and many enthusiastic participants asked for a second edition. Hence, a second scientific speed date will be organised on 19 October. This scientific speed date will be organised in connection with the Day against Cancer (which in turn takes place in Flanders on 20 October). We all realise that our struggle against cancer is only going to be won in a multidisciplinary effort. Within the LKI, we are blessed with a truly exceptional range of expertises, ranging from basic to translational to clinical cancer research. To find solutions to the many unsolved riddles, it is mandatory that all persons along this research chain should find each other. The scientific speed date is an excellent occasion to find the expertise you are looking for. But even more importantly (as we have experienced in the first speed date), it provides a forum for the set up of entirely unexpected collaborations! 
 
Committee agenda

Focus group meetings - an excellent way to foster novel collaborations
The LKI strongly emphasises the strategic advantage of focus groups as a means for gathering critical mass for its various research lines. These focus groups bring together researchers with various backgrounds (basic, translational, clinical) around a common focal research topic. 
Some of these groups have a fixed pre-planned meeting schedule, other groups have an ad hoc meeting schedule based on Doodle polls. Below, we give an overview of the current focus groups (additional ones are in the pipeline), together with their chairpersons and (where appropriate) additional management contacts. Any LKI member with an interest in one or more particular focus groups can join such a group. 
In view of the upcoming summer season, there are no focus group meetings to be announced at the moment. However, you can always contact representatives of the focus groups (see table below) to join and to have yourself put on the mailing list for future meetings. 
 
PEARL (prostate cancer)

Chair: Prof. Karin Haustermans
Management: Dr Sophie Isebaert 

Rectal cancer

Chair: Prof. Karin Haustermans
Management: Dr Annelies Debucquoy

Renal/Bladder cancer

Chair: Prof. Steven Joniau
Management: Dr Murat Akand

Head & Neck Cancer Chair: Prof. Vincent Vanderpoorten
Tumor Immunology Chair: Dr An Coosemans
Hematological malignancies Chair: Prof. Kim De Keersmaecker
Cancer epigenetics Chair: Prof. Lode Godderis
Breast Cancer  Chair: Prof. Hans Wildiers
Gynecological malignancies (ovarium, cervix, endometrium) Coordinator: Dr Daniela Annibali
Patient derived cancer models (e.g. PDX) Coordinator: Dr Els Hermans
Cancer and cognition Chair: Dr Sabine Deprez
Soft tissue sarcomas

Chair: Prof. Patrick Schöffski
Management: Dr Agnieszka Wozniak

Cancer drug discovery & therapeutics Chair: Prof Dirk Daelemans

 

 
In the media


Peter Carmeliet named one of the "50 Belgians that will save your life" in De Tijd newspaper and featured with special interview in the De Tijd series "Cancer, the curable disease".
In this interview, Peter shared his idea that blocking angiogenesis cannot be curative and even more: in conditions that block angiogenic signaling, tumor cells will always find other ways to promote angiogenesis. Moreover, starving cancer cells of nutrients can contribute to their invasion and metastasis, since such starved cells will be inclined to migrate towards the most optimal biotope. In that view, blood vessel normalisation may be a much better approach, because it would decrease the incentive for cancer cells to "move out". Peter reminisced about the huge risk he took a few years ago with this revolutionary idea, which now is gathering further momentum. See 50 Belgians..., and "Cancer, the curable disease"

Lode Godderis' research on work related cancer featured in the Tijd and at EU-Conference "Preventing work-related cancer" 
Lode Godderis wrote an op ed in De Tijd about carcinogenic factors at the work place. It is estimated that around 2000 of the 27000 annual cancer deaths in Belgium are work related. This is probably an underestimation, because this is not only a difficult diagnosis, but we also have a limited insight in the carcinogenic properties of substances encountered at work. Linking cancer and work is often difficult, not in the least because of the long delay between exposure and disease. Many workers are exposed daily to compounds for which no data are available about their potential carcinogenicity. Since 1971, only 900 compounds have been evaluated by the IARC, and 179 of these were classified as very likely or certainly carcinogenic and 285 as possibly carcinogenic. For many compounds the data are contradictory. Instead of taking effective measures because of existing suspicion for a compound (a logical decision in view of prevention), there is often a delay before policy makers take decisions. It would be recommendable to establish well defined exposure limits for workers. In this regard, EU Commisioner Marianne Thyssen has taken an important step with her proposal to limit the exposure to 13 carcinogenic chemicals at work. This measure was also discussed at the recent EU conference "Preventing Work-Related Cancer), where Prof. Lode Godderis was one of the key scientific speakers. See also interview video

Marlies Vanden Bempt explains in the TV program "Iedereen Beroemd" (VRT) her PhD research about acute lymphoblastic T-cell leukemia (T-ALL). 
We all know the importance of science communication towards the general lay public. In its section "Poepsimpel" of the "Iedereen Beroemd" program, the VRT television channel offers scientists a forum to explain their research in 2 minutes in simple (but scientifically correct) terms. Marlies Vanden Bempt (from the lab of Jan Cools) took up the challenge, and she did brilliantly! See the video!



 

Funding opportunities


KU Leuven launches call to departments and individual professors to actively scout for external top talents.
The KU Leuven offers long-term academic positions and competitive salaries to promising as well as established internationally recognized top researchers that are successful in obtaining a grant from the European Research Council (ERC), to pursue cutting-edge research in Leuven (dowload pdf version or call brochure). More info. 

Psycho-Social Research projects form Kom Op tegen Kanker (deadline 29/8/2016) 
Funding for research projects or a combination of research and care projects. Aim: contribution to better quality of life for the current or former cancer patient, via targeting of psychosocial, paramedic and/or social needs. Medical-oncological projects are not financed via this channel. More info

Scientific Award Foundation AstraZeneca - Oncology 2016 (deadline 1 Sept 2016)
The Foundation AstraZeneca attaches great importance to promoting research into oncology. On the initiative of the Foundation AstraZeneca, the FWO and F.R.S.-FNRS will in 2016 award a scientific prize in recognition of innovative research in this area. More info.

Pink Ribbon Fund - Improving the outcome of breast cancer treatments in terms of patient quality of life (28/9/2016)
The Pink Ribbon Fund wants to improve the quality of life of breast cancer patients, and more in particular after treatment: consequences of treatment, impact of side effects, and how these can be managed to maintain an optimal quality of life. This year, the Fund intends to support a project aiming to improve quality of life during and after breast cancer chemotherapy. More info

EMBO Women in Science Award 2017 (European Molecular Biology Organization)(deadline 1/10/2016) 
The FEBS | EMBO Women in Science Award highlights major contributions by female scientists to life sciences research. Winners of the award are inspiring role models for future generations of women in science. The award is a joint initiative of EMBO and the Federation of European Biochemical Societies (FEBS) . Each year the exceptional achievements of one woman working in the life sciences in Europe will be rewarded. The winner will receive 10,000 euro, a bronze statue and the opportunity to give a plenary lecture at the FEBS Congress. More info.

Cancer Research Institute - CRI Irvington Postdoctoral Fellowship Program (deadline 3/10/2016). 
The Cancer Research Institute (CRI) is the world's only nonprofit organization dedicated exclusively to harnessing the immune system's power to conquer all cancers. This important work has led to a promising new class of cancer treatments called cancer immunotherapy.CRI awards research grants and fellowships to support scientists at leading research universities and clinics around the world. More info

Fonds Yvonne Smits (King Boudouin Fund) for thyroid disease (deadline 4/10/2016).
The Fund Yvonne Smits was established to support research on thyroid diseases. The call 2016 concerns research aimed at a better understanding of thyroid diseases or at improving the diagnosis and/or the treatment of thyroid diseases. Research can be endocrine-oriented or focused on thyroid cancer.  More info.

IARC Postdoctoral Fellowships for Cancer Research (next call opens in Sept 2016). 
Applications for training Fellowships are invited from junior scientists wishing to complete their training in those aspects of cancer research related to the Agency’s mission: to coordinate and conduct both epidemiological and laboratory research into the causes and prevention of cancer. Disciplines covered are: epidemiology (including genetic and molecular), biostatistics, bioinformatics, and areas related to mechanisms of carcinogenesis including molecular and cell biology, molecular genetics, epigenetics, and molecular pathology. There is an emphasis on interdisciplinary projects. More info. 

Worldwide Cancer Research
Worldwide Cancer Research is a charity which funds research into any type of cancer anywhere in the world. For more information, see here.  

Publications


Loss of Chromosome 8p Governs Tumor Progression and Drug Response by Altering Lipid Metabolism by the team of Anna Sablina in Cancer Cell.
In a typical cancer cell, up to one-quarter of the genome is lost due to large chromosomal deletions, while the concomitant loss of hundreds of genes creates vulnerabilities that are impossible to reveal through the study of individual genes. Prof. Anna Sablina and her team optimized a workflow for the generation of cell lines with targeted chromosomal deletions (corresponding to deletions commonly observed in patients). This approach is in contrast to all other current approaches where only individual genes or non-coding RNAs are studied. To their surprise chromosomal deletions led to phenotypes that are completely different from what was found from the studies of single genes or micro-RNAs, indicating that chromosomal deletions should be considered as distinct mutational events. This  will make it possible to generate a library of human cells that represent the diversity of genomic abnormalities observed in cancer cells. This approach will maximize the efficiency of large-scale functional genomics efforts and accelerate the functional annotation of the human cancer genome. The generated isogenic cells will also represent a useful platform to identify drugs that selectively kill tumor cells harboring a particular chromosomal abnormality.  See their paper in Cancer Cell. 

Melanoma addiction to the long non-coding RNA SAMMSON by the team of Chris Marine in Nature
The known oncogene MITF is found in the 3p13–3p14 region of chromosome 3 that is amplified in melanomas and associated with poor prognosis. This study shows that a long non-coding RNA, SAMMSON, also lies in this region and is co-gained with MITF. SAMMSON interacts with p32 and thereby affects mitochondrial function in a pro-oncogenic manner. Interestingly, SAMMSON is absent in normal melanocytes, but expressed in 90% of all malignant melanoma cases. SAMMSON depletion sensitizes melanoma cells to MAPK-targeting therapeutics in vivo and in patient-derived xenograft models, by disrupting vital mitochondrial functions. These results point to SAMMSON as a potentially useful biomarker for malignancy and as an anti-melanoma therapeutic target. See their paper in Nature. 

Recurrent MALAT1-GLI1 oncogenic fusion and GLI1 upregulation define a subset of plexiform fibromyxoma by the team of Maria Debiec-Rychter in the Journal of Pathology.
Plexiform fibromyxomas are rare and benign mesenchymal gastric tumours. Characteristically, these tumours have a multinodular/plexiform growth pattern and contain areas of myofibroblastic-type spindle cells embedded in an abundant myxoid matrix, rich in capillary-type vessels. Before this study, the molecular/genetic features were unknown. Now, the Debiec-Rychter team describe a recurrent translocation t(11;12)(q11;q13) involving the long noncoding gene MALAT1 (metastasis associated lung adenocarcinoma transcript 1) and the gene GLI1 (glioma-associated oncogene homologue 1) in a subgroup of these tumours. The truncated GLI1 protein is overexpressed and retains its capacity to transcriptionally activate its target genes, giving activation of the Sonic Hedgehog signalling pathway. See their paper in J. Pathol.

The impact of adjuvant chemotherapy in older breast cancer patients on clinical and biological aging parameters by the team of Hans Wildiers in Oncotarget.
The incidence of breast cancer increases with age. While adequate treatment options are available for the elderly, concerns over side effects or the idea of futility result in lower use of adjuvant chemotherapy in the elderly population. Therefore, the team of Hans Wildiers investigated whether these concerns/ideas are justified. They investigated Quality of Life, as well as leukocyte telomere length (a marker of a cell's and by extension a person's biological age) and several inflammatory mediators (reflecting the increasing low grade chronic inflammatory status with increasing age). Importantly, demonstrate that although some biological markers do change during and after chemotherapy, there is no convincing evidence of a clinically relevant acceleration of the aging process. This is an important finding because it emphasizes that chemotherapy should not be denied to older breast cancer patients solely because of their advanced age. See their paper in Oncotarget
 
Gastric cancer by Eric Van Cutsem, Xavier Sagaert, Baki Topal, Karin Haustermans and Hans Prenen, a Seminar article in The Lancet
The Lancet Seminars are prestigious, clinically focused cutting-edge reviews of medical topics, in which key opinion leaders provide up to date and balanced discussion of a disease. In their current seminar, Eric Van Cutsem et al. present an update of the causes, classification, diagnosis, and treatment on gastric cancer, one of the leading causes of cancer-related death worldwide. See their paper in The Lancet
 
Genomic and epigenomic analysis of high-risk prostate cancer reveals changes in hydroxymethylation and TET1 by the team of Frank Claessens (together with the PEARL focus group) in Oncotarget
The clinical heterogeneity of prostate cancer makes it difficult to identify those patients that could benefit from more aggressive treatments. This study aimed to identify changes that are associated with the development of high-risk disease, via exome sequencing and copy number determination of a clinically homogeneous cohort of 47 high-risk prostate cancers. In seven cases, genomic aberrations were discovered in the TET1 (Ten-Eleven Translocation 1) gene which encodes a DNA hydroxymethylase than can modify methylated cytosines in genomic DNA and thus is linked with gene expression changes. TET1 protein levels were reduced in tumor versus non-tumor prostate tissue in 39 of 40 cases. Low TET1 mRNA levels were significantly associated with worse metastasis-free survival. Also, a strong reduction in hydroxymethylated DNA was seen in tumor tissue in 27 of 41 cases. See their paper in Oncotarget
 
Generation of the Fip1l1–Pdgfra fusion gene using CRISPR/Cas genome editing in the journal Leukemia by the team of Jan Cools
Usually, the cellular effects of oncogenic fusion proteins generated by chromosome changes (translocations, deletions) are being studied by overexpression of a plasmid encoding the fusion gene in a cellular system. In this paper, the Cools team demonstrated that the CRISPR/Cas genome editing system can be used to study the effects of fusion genes without the need for ectopic overexpression of such fusion genes. See their paper in Leukemia
 
Antivascular and antitumor properties of the tubulin-binding chalcone TUB091 in Oncotarget by the team of Sandra Liekens (Rega)
This study investigated the microtubule-destabilizing, vascular-targeting, anti-tumor and anti-metastatic activities of a new series of chalcones, whose prototype compound is  TUB091. X-ray crystallography showed that these chalcones bind to the colchicine site of tubulin and block microtubule formation. Accordingly, TUB091 inhibited cancer and endothelial cell growth, induced G2/M phase arrest and apoptosis at 1-10 nM. However, its low aqueous solubility precluded in vivo evaluation.
Therefore, a water-soluble L-Lys-L-Pro prodrug derivative of TUB091 (i.e. TUB099) was synthesized, inspired by the solubility improvement of antiviral drugs by such L-Lys-L-Pro dipeptides (which are removed by endogenous dipeptidases). This compound showed potent antitumor activity in melanoma and breast cancer xenograft models by causing rapid intratumoral vascular shutdown and massive tumor necrosis. TUB099 also displayed anti-metastatic effects. This novel class of chalcones represents interesting lead molecules for the design of vascular disrupting agents (VDAs). Moreover, this prodrug approach may be valuable for the development of other anti-cancer drugs as well. See their paper in Oncotarget
 
Nuclear p16INK4a expression predicts enhanced radiation response in head and neck cancers by the team of Sandra Nuyts in Oncotarget
A previous study by the same team showed that p16INK4a inhibits the DNA repair response independently of its function in the cell cycle, suggesting that p16INK4a subcellular localization should be considered during stratification of HNSCC patients. The rationale being that a nuclear localised p16INK4a would increase the cellular damage caused by radiation. In this study they showed that nuclear p16INK4a, but not cytoplasmic p16INK4a impaired RAD51 foci formation, indicating that nuclear localization of p16INK4a is crucial for its function in DNA repair. In a retrospective cohort of HNSCC paients, only patients expressing nuclear p16INK4a expression showed better outcome, locoregional control and disease free survival, after chemoradiation. Thus, nuclear p16INK4a expression is a potent marker to predict radiation response of HNSCC patients and should be taken into account in intensification or de-escalation studies. See their paper in Oncotarget
 
miR-17-92/p38α dysregulation enhances Wnt signal and selects Lgr6+ cancer stem cell like cells during human lung adenocarcinoma progression by the team of Juan-José Ventura in Cancer Research
Defining the molecular and cellular roots of lung cancer relapse after initial treatment remains an imperative to improve survival. In this paper, the Ventura team reports that the lung stem cell marker Lgr6 becomes enriched in non-small cell lung cancer (NSCLC) cells during malignant progression. Lgr6+ NSCLC cells displayed self-renewal and differentiation properties along with a higher tumorigenic potential. Mechanistic investigations suggested that a defective repression of the miR-17-92 gene cluster was responsible for evolution of a selection for outgrowth of Lgr6+ NSCLC cells. High levels of expression of miR-19 family members were found to target and downregulate levels of p38α kinase, providing a specific survival signal for Lgr6+ cells as mediated by increased Wnt/ß-catenin activity. Our results identify a specific stem-like cell population in NSCLC with increased malignant potential, which could be the subject for the development of novel diagnostic/prognostic tools and for novel targeted treatments. See their paper in Cancer Research
Lectures in Leuven

Aging, immunosenescence and stromal senescence and the development and treatment of breast cancer in elderly by Barbara Brouwers
PhD Defense (Prom. Prof. Hans Wildiers, Co-promotor Prof. Diether Lambrechts)
When: 21.06.2016, 18h00   Language: English   Where: Aula van de Tweede Hoofdwet, 01.02, Kasteelpark Arenberg 41, 3001 Heverlee
More info
 
Acetyl-CoA at the crossroads of cell metabolism, signaling and epigenetics
Kathryn Wellen, PhD Abramson Family Cancer Research Institute, University of Pennsylvania, Philadalphia, USA
When? Thursday, 23 June, 2016 -16:00 to 18:00
Where? O&N4, Auditorium 04.330 - O&N4

Decoding gene regulatory programs of cellular decision making
Stein Aerts (Laboratory of Computational Biology)
When? Friday,  24 June, 2016 - 13:00-14:00
Where? O&N4, Auditorium 04.330 - O&N4

Cancer & Neuro Program Progress seminars
Integrative and comparative genomics indentifies new melanoma tumor suppressor genes by          Michael Olvedy (Chris Marine lab)
Role of B55alpha in endothelial cells: implications for disease and development
by Manuel Ehling (Max Mazzone lab)
When? Tuesday, 28 June, 2016 - 13:00-14:00
Where? O&N4, Auditorium 04.330 - O&N4

Title to be announced
Daniel Peeper,
Division of Molecular Genetics, Netherlands Cancer Institute and VUmc Amsterdam, The Netherlands (host: Chris Marine)
VIB & KU Leuven Distinguished Lecture Series
When? 21 September, 2016, 16:00-17:00
What? Daniel Peeper’s research group develops and uses function-based oncogenomic approaches to ask clinically relevant questions, aiming to dissect cancer-driving genetic networks for drug target and biomarker discovery. For example, we are exploring ways to enhance the activity, or avoid resistance, of currently used targeted clinical compounds. Recently, they have also begun building experimental systems to develop combinatorial targeted and immunotherapeutic therapies.
Where? O&N4, Auditorium 04.330 - O&N4
Conferences

Hallmarks of Cancer
December 11-13, 2016 - Ghent, Belgium
more info here

Job opportunities

PhD position in Bioinformatics
(P. Carmeliet lab). More info
Post-doctoral scientist - Decoding new targets in angiogenesis (M. Santoro Lab) More info
PhD position on pre-clinical intratumoral antibody gene transfer (at the Laboratory for Therapeutic and Diagnostic Antibodies, Prof P. Declerck and Dr K Hollevoet ) More info
Unraveling the genetics of familial schwannomatosis (PhD student position) at Human Genetics, Prof.Legius) More info
Postdoc position: (deep) learning the genomic regulatory code (Prof. Stein Aerts lab, see www.aertslab.org) More info
Quality assurance for online adaptive proton therapy (Prof. Dr. Edmond Sterpin, Laboratory for Experimental Raditherapy) More info
Exploring nuclear-cytoplasmic transport as cancer therapy (Prof Dirk Daelemans, Laboratory of Virology and Chemotherapy at the Rega Institute) More info
Importance of LEDGF for the development of acute leukemia (division of Molecular Medicine , Prof Zeger Debyser and Dr Jan De Rijck) More info
Send us your news!

The LKI is a very large community. Therefore, the efficient spreading of news is of paramount importance. You can help us by sending us your news! This can come in all sorts, such as (non-exhaustive list):
- prizes, grant awards, honours: any news on your well deserved scientific prizes, grants for instrumentation that will be beneficial for many of us, appointments in scientific societies or in associations that promote cancer research fundraising, ...
- upcoming events at LKI: are you organising a workshop, course, social activity... let us know!
- committee meeting agendas: send us your information regarding meetings of your focus group, your task force, ...
- new faces at LKI: we are very keen to announce the arrival of new principal investigators, clinical staff members, administrators etc etc 
- media coverage: let us know if you have news appearing in the media (newspapers, TV. ...)
- funding opportunities: we're always keen to know if you spotted some new pot of gold ;-).
- collaboration partner search: if you are looking for partners for collaboration on a particular topic, please let us know. 
- publications: send us your breakthrough publications!
- lectures: we are interested in any cancer related lectures that you happen to organise!
- conferences & symposia: if you come across conferences and symposia (in Belgium or abroad) that are of potential broader interest to the LKI community, do let us know!
- job opportunities: help us spread the news about job openings in your team by sending us the link to the advert!
- ....

Please send your news to the editor of this newsletter:
Coordinator of Translational Cancer Research
Prof Dr Johan Van Lint
016/330820
johan.vanlint@kuleuven.be