Fighting Cancer on All Front LinesCREATE Health, a Strategic Centrefor Translational Cancer Researchin Lund, creates a substantialsocial impact for patients,through direct application ofresearch for selection of optimal,individually-based, cancer diagno-ses and treatments.

CREATE Health (Strategic Center for Cli-nical Cancer Research using EmergingAdvanced Technologies for Health) is amulti-disciplinary strategic research centreat Lund University started almost ten yearsago. The centre, today mainly located atMedicon Village, integrates clinicianswith researchers from the Faculties of Me-dicine, Natural Sciences and Engineeringat Lund University, using a superbly equ-ipped and integrated ’omics’ platform.”All competencies are needed to fight

cancer,” says Research Coordinator, DrUlrika Andréasson.The centre uses an integrative approach

to develop novel diagnostics and therapeu-tics, based on identified markers and mo-lecular signatures.

Early DiagnosisOne of the centre's main focus areas is ear-ly diagnosis. There’s a lot to be gainedfrom an early discovery of cancer sinceearly diagnosis is a key to the outcome of acancer treatment. For example, pancreaticcancer is generally detected at a very latestage and the five-year survival rate is only3-4%. The late detection is due to unspeci-fic symptoms and lack of markers for ear-ly diagnosis. One of CREATE Health’smost important achievements during lastyears is the discovery of a serum biomar-ker signature that identifies pancreaticcancer in a blood sample, forming the ba-sis for an early diagnostic test. ”The biomarker signatures consist of

18-20 proteins, which give us a muchmore precise indication than individualproteins do. The biomarker signature accu-rately distinguishes between pancreaticcancer patients and healthy controls andhas also the capacity to distinguish cancerfrom inflammation in the pancreas,” Ulri-ka Andréasson comments.The project is led by the centre’s direc-

tor Professor Carl Borrebaeck, who haspublished articles and reviews in the rese-arch fields of antibodyengineering, immunothe-rapy, and affinity proteo-mics.

The SCAN-BInitiativeA project that was initia-ted and is led by anotherof the centre’s principleinvestigators, ProfessorÅke Borg, is the breastcancer project SCAN-B.It’s a multi-centre colla-boration that started in2010, today between hos-pitals in Malmö, Lund,Helsingborg, Växjö,Halmstad, Kristianstad,Karlskrona and Uppsala,and continues to includemore hospitals. The long-term goals of

the project are to developnew diagnostic, prognos-tic, and treatment-predic-tive clinical tests for bre-ast cancer. These goals

will be accomplished using the latest ad-vanced genomic technologies to study themolecular profiles of breast tumour sam-ples from patients on a prospective basis.

All patients with suspected or diagnosedprimary breast cancer, in the southern he-althcare region of Sweden, are eligible andmay be enrolled in the study, following in-formed consent. Participation means that ablood sample is drawn prior to surgery;then following surgical removal of the can-cer, a small piece of the patient's tumour issent for genomic analysis. ”Today, samples from nearly 5,000 pati-

ents have been collected. RNA and DNAsequencing give the molecular profile ofthe tumour. Cancer is really a collectiveterm for hundreds of diseases, breast can-cer alone can be divided into several sub-groups,” states Ulrika Andréasson.Due to the large heterogeneity of the

disease, analysis of thousands of molecu-lar profiles of individual patient tumoursare needed to be able to develop the mosteffective and beneficial treatments and di-agnostic tests to improve patient survival

and quality of life. ”In the first phase, we have commenced

whole-transcriptome gene expression pro-filing using massively parallel sequencingof tumour RNA (RNA-seq). The aim is todevelop new valuable biomarkers and pro-vide them to the clinic on a routine basis,”tells Prof. Åke Borg.As an example, patients with HER2-po-

sitive breast cancer, one of the most ag-gressive forms, are treated with targeteddrugs towards HER2. Some patients bene-fit from these drugs, others need more orother treatment. By identifying the diffe-rent subgroups physicians can optimisethe clinical handling and researchers candevelop targeted treatments that are moreeffective. ”Cancer treatment is expensive, so gi-

ving the right treatment to the right patientwill save a lot of public spending and, evenas important, save patients from unneces-sary suffering,” Åke Borg adds.The SCAN-B project is made possible

by funding provided by the Berta KampradFoundation, Swedish Cancer Society andCREATE Health.

Database of Breast TumourProteinsIn the SCAN-B project, the cancer geno-me is analysed. However, the researchersat CREATE Health are also about to pu-blish the first version of their Breast Can-cer Index. It’s a database of all the proteinsfound in the breast tumour tissues. Thedata is collected by mass spectrometry andthe aim is to understand the proteins’ func-tions, signal pathways and why the tu-mours respond differently to the same tre-atment.

Principal investigator of the Breast Can-cer Index is Professor Peter James, whoholds several patents in proteomics metho-dologies and is engaged in the research fi-eld of protein analysis with a focus on pro-tein-protein interaction, non-gel proteo-mics, membrane proteins and methods de-velopment for clinical proteomics.

ConclusionThe research teams at CREATE Healthhave made several significant achieve-ments. Future work with a diagnostic testfor pancreatic cancer will now be perfor-med by Immunovia AB, a spin-out compa-ny, potentially having a test on the marketwithin a couple of years. The mapping ofbreast cancer, both the genes (SCAN-B)and the proteins (Breast Cancer Index), iscrucial for improving diagnosis and treat-ment of breast cancer patients in the futu-re.In addition, Ass. Professor Sara Ek at

CREATE Health has identified the proteinSOX11 as a potential tumour suppressor inmantle cell lymphoma and ovarian cancer.SOX11 shows a great potential to be usedas a clinical relevant biomarker especiallyto diagnose and stratify mantle cell lym-phoma patients. Professor Sven Påhlman, one of CREA-

TE Health’s PIs, has identified the proteinHIF-2α as a marker of and therapeutic tar-get for neuroblastoma stem cells.”The goal is to target HIF-2α to fight

neuroblastoma as well as the related tu-mours paraganglioma and pheochromocy-toma,” says Sven Påhlman.

MAD for CancerCancer research is not a one man’s job andone recent and larger initiative is the MAD(Make A Difference) for Cancer program-me, a unique concept bringing several dif-ferent faces of cancer biology from fourdifferent faculties at Lund University to-gether in a multifocal approach to fightcancer.MAD for Cancer is based on the insight

that a tumour cannot be regarded as mere-ly a collection of cancer cells, but that itconstitutes an organ in itself. Hence, thestrategy to fight cancer is to combineknow-how from areas involving all partsof the tumour environment; such as,genomics, proteomics, chemical biology,cancer stem cells, and stromal biology.

Website: www.createhealth.lth.se

14 MEDICON VALLEY 2020 AFFÄRSTIDNINGEN NÄRINGSLIV

Blood samples divided into healthy controls and cancer patients based on the expression ofdifferent proteins in the blood sample. Red colour equals a large amount of the protein andygreen colour equals a small amount of the protein

Dr. Ulrika Andreasson, Research Coordinator.

Prof. Carl Borrebaeck, Director of CREATE Health.

Facts:CREATE Health wasestablished in 2006after a grant from theSwedish Foundationfor Strategic Research(SSF). CREATE Healthwas able to continuethe work after thefive initial years aftera grant from VINNO-VA.