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Home , Oncology

Photo: H. Flank

WELCOME TO THE DEPARTMENT OF ONCOLOGY-

Photo: S. Ceder

Photo: Erik Cronberg

Photo: H. Flank Photo: E. H. Cheteh & S. Ceder

t. Solnat. JohanOlofWallins väg

SKALA

Solregnsvägen 0255075 100 125 m

Solna kyrkväg Solnavägen

Prostvägen

1 Prostvägen DEPARTMENT OF Fogdevreten

ONCOLOGY-PATHOLOGY Prostvägen Granits väg Science for Life Laboratory We are a part of Karolinska Institutet, where we work with research and offer Solna kyrkväg educational programs at undergraduate, Master and doctoral levels. Uniting more Tomtebodavägen than 30 research groups, the department´s broad focus on cancer combines basic, translational and clinical research, ranging from mechanisms of cancer development and biomarkers to development of new technologies for precision cancer . Spårområde Karolinska vägen

Thus, our goals are, based on fundamental discoveries, to identify and implement Nobels väg Tomtebodavägen cancer biomarkers supporting early diagnosis and improved personalized , Widerströmska building and to drive drug discovery via innovative clinical trials. Further, we engage in edu-Tomtebodavägen cation of next generation scientist and healthcare professionals in these areas.P Our research teams are mainly located at two research buildings, Bioclinicum and Science for Life Laboratories (SciLifeLab), Solna, and at buildings including

Pathology unit and New Karolinska Hospital (NKS), Stockholm. In addition, few Scheeles väg Theorells väg research groups form satellites in Södersjukhuset, Karolinska hospital in Huddinge 3 and at Cancercentrum Karolinska, Solna. Karolinska vägen

Scheeles väg

Retzius väg

Nobels väg Biomedicum Solnavägen

Science for Life laboratories Individual research groups are part of both

the department of Oncology-Pathology and Tomtebodavägen the SciLifeLabs national infrastructure. Karolinska vägen Bioclinicum Berzelius Laboratory Bioclinicum Aula Medica We are located on floors 5 and 6 with Karolinska vägen skyways connecting us to NKS, Karolinska Institutet campus Solna and Biomedicum. Akademiska stråket Berzelius v äg Nanna Svartz väg Pathology and NKS

We combine our responsibilities Nobels väg Karolinska with education at doctoral and postdoctoral University Hospital levels, clinical research and clinical trials. von Eulers väg

Nobels väg Berzelius väg Berzelius Photos: H. Flank

von Eulers väg

Ryssmuren

Berzelius väg

t. Stockholm

Norra Länken At SciLifeLab, we develop novel technologies and high OUR RESEARCH AREAS throughput platforms in the areas of proteomics, drug discovery and drug development. We use these platforms for discovery of novel anti-cancer drugs and of biomarkers At Bioclinicum, we focus on basic molecular mechanisms for precision medicine in cancer. We work in teams com- that underlie cellular and physiological functions under bining experts in engineering, chemistry and data science normal conditions and during development and progression with oncologists, nurses and as part of precision of cancer. Specifically, we study types and processes cancer medicine program across several different cancer involved in cancer development and progression, including types including , , lung, , ovarian, cancer cells and cancer initiating cells, cancer-associated and . stroma cells, such as fibroblasts, endothelial cells and angio- genesis, immune cells and inflammation, cell migration and . We conduct pre-clinical and translational studies to validate basic findings in in vivo models and in tissues, and implement our discoveries in clinical trials. Bioclinicum

SciLifeLab

NKS and Pathology

Photos: H. Flank At NKS and Pathology, we conduct clinical research and clinical trials for better and early cancer diagnosis, and to discover novel predictive biomarkers for more efficient and personalized anti- cancer treatments. Combining our clinical expertise with research allows fast introduction of novel findings for the benefit of cancer patient. Our clinical studies result in discoveries of novel diagnos- tic and prognostic measurements and their implementation into clinical practice. Oncologists and pathologists develop and evalu- ate novel targeted and collect tumor tissues and samples into Biobanks for both on-going and future translational research projects. OUR GOALS AND STRENGTHS

WHAT WE WANT TO DO OUR STRENGTHS Our MISSION is to improve diagnostics, treat- • Translating basic knowledge and discoveries ment and quality of life for patients with cancer Clinical Novel drug into practice through basic, translational and clinical research • Improved and personalized cancer diagnostics and education in the field of cancer. development and clinical and • Ex vivo drug screenings for precision medicine • Immune and therapy trials treatments HOW WE WANT TO DO IT Improved • Clinical trials validating novel drugs and drug Our GOALS are to achieve excellence in research combinations and education, to foster clinical research and to diagnostics • Novel treatment regimen for improved quality create high technological platforms for research and precision of life support and innovation. medicine • New drug development and therapies Strong Basic • High quality courses and educational programs • Nurturing junior scientists for future leadership Our VALUES are based and on ethics, high diversity Translational and equality. We culti- vate openness, networ- research Lars Holmgren, king and collaborations New the Head of our Department, says: to consolidate national and international forces technologies and to cure cancer. big data-driven research

We share skills, knowledge and resources through national and international networks, collaborations, OUR NETWORKS ARE: conferences, courses and seminars and Photo: H. Flank Cancer Research KI – network at Karolinska institutet by building strong and ki.se/en/cancerresearchki/cancer-research-ki advanced modern technological platforms.” Cancer Core Europé – European Cancer Association cancercoreeurope.eu/karolinska SOME OF OUR DISCOVERIES AND ACHIEVMENTS

Theo Foukakis, CLINICAL CANCER RESEARCH MD and a Team leader in J. Bergh group, says:

THE PANTHER TRIAL AND BEYOND PHASE 1 TRIAL WITH TUMOR FOR HIGH-RISK INFILTRATING LYMPHOCYTES Our mission is that all women with breast cancer Cancer clinical trials are conducted at the AND DENDRITIC CELLS Department in collaboration with the will be cured with minimal negative of cancer has achieved HRQoL effects from the treatment. Karolinska University hospital. One aspect substantial progress, particularly when the We therefore continue our clinical research in these trials is the patients’ health-related Immune Checkpoint Inhibition, ICI, was quality-of-life (HRQoL). It is a very important introduced. This prolongs the survival of that includes novel therapeutic regimens parameter as it is a combination of the tre- some patients with advanced . and a careful follow-up of the combined atment outcome and the patient’s subjective For those who fail, we are developing a new disease and quality of life parameters to experience of the disease and the treatment combination of two types of immuno-the- improve the clinical management that helps to inform patients in the treat- rapies. First, T-cells are extracted from the of breast cancer.” ment decision. The Panther trial in women patient’s tumor. These “Tumor Infiltrating with high-risk early breast cancer showed a Lymphocytes”, TILs, an important part of better event-free survival in a group recei- the body’s immune defense against cancer, ving tailored dose-dense as are multiplied up to 50 billion cells and compared to standard adjuvant chemothe- administered back to the patient in combi- 1 rapy , but a lower HRQoL level during the nation with Interleukin-2. What makes this treatment1. However, a long-term follow up study unique compared to other clinical Stina Wickström, revealed that HRQoL levels recovered once TIL trials is that the patients are at the same head of TIL production and immune monitoring, comments: 2 treatment was terminated . A meta-analysis time treated with several doses of a tumor further showed that increasing the dose vaccine consisting of dendritic cells, DC, density of adjuvant chemotherapy was safe which activate the immune system and give and resulted in fewer disease recurrences the injected TILs an extra boost. Of the four 3 and fewer deaths from breast cancer and severely ill patients with malignant me- Our clinical may therefore be more frequently used. lanoma that failed to respond to any other study has shown that Cell therapy For women offered this treatment it will be treatment, three have responded with a with T-cells and DC vaccine has reassuring to know that although HRQoL complete or near complete remission while remarkable strong clinical effects on decreases during the treatment, an impro- patients treated with TILs mono-therapy metastatic advanced malignant melanoma. vement and recovery is expected after the did not have the same favorable response. treatment. We hope that the same approach will be The method is a part of Karolinska Univer- efficient in other solid tumors, such as 1. Foukakis T, et al. Effect of tailored dose-dense chemotherapy sity Hospital’s efforts in cell-based therapy, gynecological cancer. This demonstrates vs standard 3-weekly adjuvant chemotherapy on recurrence- and Rolf Kiessling, head of the study, has free survival among women with high-risk early breast cancer: applied to the Swedish Medical Products the strength of interdisciplinary A randomized clinical trial. JAMA 2016; 316: 1888-96. collaborations between basic scientists 2. Brandberg Y, et al. Long-term (up to 16 months) health-rela- Agency for approval to test the method on ted quality of life after adjuvant tailored dose-dense chemothe- other types of metastatic cancer. and clinicians at Karolinska hospital rapy vs. standard three-weekly chemotherapy in women with in Solna and Huddinge.” high-risk early breast cancer. Breast Cancer Res Treat 2020; 181: 87-96. 3. Early Breast Cancer Trialists’ Collaborative Group Lövgren T, Wolodarski M, Wickström S et al., Complete and (EBCTCG). Increasing the dose intensity of chemotherapy long-lasting clinical responses in immune checkpoint inhibi- by more frequent administration or sequential scheduling: a tor-resistant, metastasized melanoma treated with adoptive patient-level meta-analysis of 37 298 women with early breast T cell transfer combined with DC vaccination. OncoImmu- cancer in 26 randomised trials. Lancet 2019: 393;1440–52. nology 2020, VOL. 9, NO. 1, 1–11 SOME OF OUR DISCOVERIES AND ACHIEVMENTS

Ulrika Warpman Berglund, NOVEL DRUG DISCOVERIES: Deputy group leader of Helleday lab, says: FROM BENCH TO BEDSIDE A collaborative work of multidisciplinary teams is the key to successfully TARGETING MTH1 TARGETING MUTANT P53 develop novel drugs BY KARONUDIB BY APR-246 in Academia” Developing novel therapies requires not The TP53 is only a unique idea, but also medicinal mutated in around 50% of all human chemistry, pharmacology and pharmacok- tumors. Can we exploit mutant p53 as inetic expertise. We work in multidiscipli- a therapeutic target in cancer? We in nary teams to combine our groundbre- Wiman group have developed a novel aking and strong basic understanding of therapeutic strategy based on pharma- cancer pathology with novel technologies cological reactivation of mutant p53. and expertise in drug discovery to perform We identified and subsequently develo- translational research and identify and ped a clinical candidate, APR-246. The develop novel anti-cancer treatments. compound is converted to the Michael acceptor, MQ, promotes p53 refolding In 2014 the Helleday team demonstrated and also causes oxidative stress, resulting that targeting the enzyme MTH1 (NUDT1) in robust death. was a promising potential anti-cancer the- rapy with very limited general toxicity. Th- We founded the company Aprea Thera- ree years later, we had developed a clinical peutics in 2003 with the aim of taking candidate, Karonudib (Karolinska NUDT1 APR-246 to clinical trials. A first-in-man inhibitor), designed clinical trial protocol phase I clinical study was initiated 2009. and obtained approvals from Medical Currently APR-246 is tested in a phase III Product Agency and Ethical Committee to clinical trial in combination with azaciti- initiate clinical trials. Presently two phase dine (AZA) in patients with TP53-mutant Klas G. Wiman, I trials are on-going at Karolinska Univer- MDS (). APR- group leader, says: sity Hospital, MASTIFF and MAATEO, with 246 has received Fast Track and Break- the primary goal to investigate safety and through Therapy designation from the of Karonudib in patients with FDA (www.aprea.com). advanced solid or hematolo- gical . Our attempts to 1. Gad et al., MTH1 Inhibition Eradicates Cancer by Preven- 1. Bykov VJ, et al., Restoration of the tumor suppressor func- reactivate mutant p53 ting Sanitation of the dNTP Pool, Nature 2014, 508:215-21 tion to mutant p53 by a low molecular weight compound. 2. Warpman Berglund et al., Validation and Develop- Nature Med 2002; 8, 282-8. led to a successful drug ment of MTH1 Inhibitors for , 2. Lambert JMR, et al., PRIMA-1 reactivates mutant p53 by candidate in advanced Ann Oncol 2016, 12:2275-2283 covalent binding to the core domain. Cancer Cell 2009; 15, 376-88. clinical development” 3. Lehmann S, et al. Targeting p53 in vivo: A first-in-man study with the p53-targeting compound APR-246 in refractory hematological malignancies and . J Photos: H. Flank Clin Oncol 2012; 30, 3633-9. 4. Bykov VJN, et al., Targeting mutant p53 for efficient cancer therapy. Nat Rev Cancer 2018; 18(2):89-102. SOME OF OUR DISCOVERIES AND ACHIEVMENTS

Päivi Östling, TOWARDS PRECISION co-PI of O. Kallioniemi group at SciLifeLab, says: MEDICINE IN ANTI-CANCER

TREATMENT We have established an efficient network and We are building a strong Precision cancer medicine (PCM) tight coordination between clinical and scientific teams, and put in place platform in collaboration with SciLifeLab, KTH, Uppsala the technical solutions to screen the tumor cells University and Karolinska University Hospital. The combi- from patients for sensitivity to a broad range of nation of molecular profiling and drug resistance testing drugs and drug combinations. can help to individualize care of patients, but can also be This is tricky but very rewarding applied to optimize drug discovery and development as when in the future the patients can well as help design clinical trials to the most promising benefit from the fine-tuned drugs in the cancer subtypes most likely to be responsive. personalized treatment”

Longitudinal -Omics Molecular pathology sample collection proteomics genomics diagnosis check-up check-upcheck-uprelapse check-up check-up transcriptomics

pleural Blood and immune cell Functional models effusion characterization Photos: H. Flank Treatment monitoring blood ctDNA tumoroids, spheroids CTCs organoids, monolayers

Ex Vivo functional testing Individualized tissue viability data integration toxicity drug-target enagagement single-cell resolution

tissue Identification of response biomarkers SOME OF OUR DISCOVERIES AND ACHIEVMENTS

Christofer Juhlin, THE WAY IN SCIENCE: MD, PhD, says: FUTURE GROUP LEADERS

Educating and supporting young scientists for a continuous future strong translational In my research, cancer research is an important goal for the department. Ambitious researchers that I am striving to uncover novel genetic become Team leaders within a research group get the support before taking the next mechanisms in endocrine tumors which step to an independent group leader. could aid in our daily work as surgical pathologists with the end goal to modernize CHRISTOFER JUHLIN NINA GUSTAFSSON endocrine pathology and implement MD, PhD, TEAM LEADER IN C. PhD, TEAM LEADER IN T. HELLEDAY comprehensive, genome-wide analyses LARSSON GROUP AT BIOCLINICUM GROUP AT SCILIFELABS of these tumors into clinical practice.” “I am an attending endocrine patholo- “I went to Stockholm University, where I gist at the Karolinska University Hospital majored in Molecular Biology. After that I responsible for diagnosing patients with continued with PhD studies in Medical Sci- tumors in endocrine (hormone-producing) ence at KI followed by postdoctoral studies in organs, such as the thyroid, parathyroid Computational Medicine, Cancer Metabolism and adrenal glands. Besides my clinical and Chemical Biology. In 2018 we discove- duties, I am also a research team leader red that the glycolytic enzyme PFKFB3 also at OncPat. My team recently discovered functions as an essential regulator of DNA that mutations of the TERT promoter repair and genomic stability. This unexpected Nina Gustafsson, are not only significantly associated with discovery resulted in a patent, and I could PhD, says: malignant thyroid tumors but can also form, with support from the Swedish Child- predict the transition from histologically hood Cancer Foundation, my research team ”benign” tumors to malignant tumors, in 2019, and I hope in the future to start my and therefore this biomarker was rapidly own independent group. introduced into clinical setting for the Most anti-cancer therapies exert We will further unravel how PFKFB3 network right diagnosis and treatment algorithms their toxicity by introducing contributes to DNA repair and provide novel for this patient category.” DNA damage. and ground-breaking biological insights into These cytotoxic effects can be the largely unexplored connection between greatly potentiated by simultaneously the DNA damage response and cancer meta- bolism beyond nucleotide metabolism.” targeting DNA repair mechanisms. This is our strategy for developing novel anti-cancer therapies” Paulsson JO, et al., Whole-genome sequencing of Gustafsson N et al. Targeting PFKFB3 radiosensitizes cancer synchronous thyroid identifies aberrant DNA cells and suppresses homologous recombination. Nature repair in dedifferentiation. J Pathol. 2020 Communications 2018; 9: 3872 Feb;250(2):183-194. Hysek M, et al., Clinical Routine TERT Promoter Mutational of Follicular Thyroid Tumors of Uncertain Malignant Potential (FT-UMPs): A Useful Predictor of Metastatic Disease. Cancers (Basel). 2019 Sep 26;11(10):1443 Photos: H. Flank Juhlin CC, et al., Parafibromin immunostainings of parathyroid tumors in clinical routine: a near-decade experience from a tertiary center. Mod Pathol. 2019 Jul;32(8):1082-1094. Mimmi Shoshan, WE TEACH CANCER Director of Undergraduate Studies, says: BIOLOGY AND ONCOLOGY

We at The Department of Oncology-Pathology are enthusiastic teachers! We are proud of Our main goal is to give the most comprehensive and state-of-the-art knowledge on mechanisms of cancer development, on cancer diagnostics and treatment the high-quality learning environment as well as technical developments in these fields. the Department offers. We have expert preclinical as well as UNDERGRADUATE EDUCATION GRADUATE EDUCATION clinical teachers who can demonstrate the links between • Courses in Tumor Biology, Medical • Courses in Oncology, Tumor Biology, basic and clinical research and clinical reality. and , advanced Tumor , Molecular They keep updating the learning and palliative treatment, and Pathology Methods, Omics, Bioinformatics. Target materials they present, and and Forensic medicine. Target groups: group: M. Sc., PhD students with full- they strive to help students KI students in Medicine and Biomedi- time research at KI be active learners.” cine and Master students at KI • National research school (NatiOn) • Commissioned courses in Tumor Bio- in clinical and translational cancer logy-related subjects. Target groups: research. Target group: M.D. PhD health care providers, pharmaceutical students with a clinical or translational research companies. project in cancer research field, M.D. Svetlana Bajalica Lagercrantz, and future clinical researchers in the Chairman of NATION, says: cancer field. • Courses for physicians in specialist training. We created this school more than 10 years ago as a unique package of courses to provide the mandatory research education for NATIONAL RESEARCH SCHOOL (NATION) IN CLINICAL medical doctors who want to combine AND TRANSLATIONAL CANCER RESEARCH clinical work and doctoral studies. With today´s rapid advances in The program offers a tailored package of courses primarily in molecular oncology and molecular oncology, doctors need to learn more research methods for MDs clinically active in the cancer field. During a total of 20 weeks about research tools in order to actively divided into blocks during three years, a solid and advanced foundation for clinical cancer participate in and lead clinical trials and studies. research is provided. Completion of this program meets the requirements of KI and most other Swedish medical universities for tuition in doctoral (Ph.D.) studies. Only research can radically improve cancer treatment based on novel discoveries and drug development, leading to a more personalized treatment of each cancer patient!” The monthly “breakfast gatherings” Once a year the Department gathers at a WORKING AT DEPARTMENT bring out the news from the Department Kick-off: a 1-day retreat full with scientific Chair and brief individual presentations presentations from the groups followed by a with the latest breakthrough research. delicious dinner. Coffee combined with poster OF ONCOLOGY-PATHOLOGY presentations and fruitful discussions inspires collaborations As a part of KI, we strive for the highest level of research combined with educational activities. At Bioclinicum, we are conveniently located between Karolinska hospital and SciLifeLabs to foster our close connec- tion with the and our urge to use state-of-art technologies. Some of the regular events that drive our people together through scientific exchange are the weekly seminars, our annual conference, and not to forget the popular monthly breakfast gatherings in the relaxed environ- ment. Our members come from different countries and an annual International party brings us together and invites to taste the home- made food from all the corners of the world. Our goal is that every- Breakfast Kick-off body is equally treated and have opportunities to pursue their ambitions in research and personal growth. gatherings International Annual Party Conference Seminars

Photos: S. Ceder

Our Annual Conference of Seminars. Friday seminars the Department, “Frontiers with both Swedish and in Cancer Research and international speakers are Therapy”, is being held for organized weekly, as well as 17 years. We invite speakers PhD students’ seminars that from Sweden and abroad. are included in PhD educa- The prizes are distributed International Party. As we tion at KI. TRAP (Translational for the best poster at the are more than 30 nationalities Research Activity Program) conference, the best Teacher united at the Department, we seminars held monthly are and the best Scientific Paper gather every year to taste the specifically devoted to clinical of the year as well as the Dan best food from all the corners and translational research. Grandér prize for the best of the world followed by games PhD thesis of the year in the and dancing Photo: H. Flank field of cancer. CONTACT Karolinska Institutet is one of the world’s leading medical universities. Our vision is to advance knowledge about life and strive towards better Have questions or interested to learn more about our research and activities? health for all. Karolinska Institutet accounts for the single largest share Contact the Head of the Department, Prof. Lars Holmgren, [email protected] of all academic medical research conducted in Sweden and offers the Want to get more information about the structure and function of our country’s broadest range of education in medicine and health sciences. department or about financial questions? Contact the Head of our Administration, The Nobel Assembly at Karolinska Institutet selects the Nobel laureates Maria Von Witting, [email protected] in Physiology or Medicine. For donations, use KI’s SWISH 123 202 32 08 or the bank account 5310-6217 and write K7 (the code of our Department) and the name of the group leader whose research you want to support. Questions? Contact [email protected] Want to enquire about the possibilities to do internship or Master at our Department, look for ads at KI home page or contact the group leaders directly. For questions about PhD education at Department of Oncology- Pathology, contact our Director of doctoral education Associate Professor Andreas Lundqvist, [email protected] or Administrator Erika Rindsjö, [email protected]

Photo: H. Flank