Research

Research groups

Stem cells and regeneration

Stem cells are responsible for regeneration in various organs. For example, blood stem cells, which are found in the bone marrow, provide all blood cells throughout life. These blood stem cells are already created during embryonic development. Despite various protective mechanisms, stem cells can suffer damage over time - especially after exposure to certain toxic substances or with increasing age - for example in the form of so-called "genetic changes" or "mutations" that alter their genetic material. In unfavorable cases, such damage confers growth advantages and allows damaged cells to spread in the bone marrow, while existing healthy cells are displaced. If further mutations are added or the bone marrow environment is damaged by the altered cells, leukemia can develop. Similar mechanisms probably take place during tumor development in other stem cell-containing organs, but are generally less well studied here.

Our research group focuses on the study of stem cells in regeneration and tumor biology. We study how stem cells arise during development, survive later in the bone marrow and - in the case of cancer - interact with the bone marrow and the cancer cells. We are particularly interested in leukemia diseases and in certain gene alterations that indicate an unfavorable clinical course in patients with leukemia (e.g. concerning the stem cell gene EVI1). Using various research models, we are analyzing the effects of these genetic changes on the leukemia cells themselves and on their interaction with healthy stem cells and the environment. In leukemias, but also in other cancers (e.g. breast and ovarian cancer), we investigate how tumor cells use stem cell properties to induce cancer and protect themselves from conventional chemo- or radiotherapies and the body's own immune surveillance.

By gaining a deeper understanding of these processes, our aim is to develop novel therapies that are also effective against resistant tumor cells with stem cell properties.

Immunotherapy

Our immune system not only keeps a number of microbial pathogens in check, it is also constantly working to identify and eliminate degenerated body cells, so-called cancer cells. But like some bacteria and viruses, which are able to outwit our immune system as part of their survival strategy, tumors also develop mechanisms to subvert the function of the immune system and avoid being detected by it. If immune cells have nevertheless invaded the area surrounding a tumor or even the tumor itself, a tumor can "disarm" the once aggressive killer cells so that they can no longer attack it. And this is precisely where modern immunotherapy comes in. So-called therapeutic monoclonal antibodies are able to "arm" such killer cells again. These antibodies bind to inhibitory receptors on a killer cell and thus prevent them from transmitting "negative" signals that are responsible for the loss of function of the killer cells. At best, the killer cells can then trigger the cell death of the cancer cell again.

We can offer our patients the latest active substances from the field of immunotherapy as part of clinical programs. Patients with a wide variety of cancers can be enrolled in clinical trials at our tumor center to give them access to cutting-edge agents. As part of our Phase I unit, we offer our patients access to drugs that are still in clinical development and are not available as part of a "standard treatment".

According to the latest scientific findings, the success of such immunotherapy depends on how many and, above all, which immune cells are present in the tumor. We are therefore developing test systems in the laboratory that enable us to better predict the effectiveness of new immunotherapies and thus facilitate the search for the optimal therapy or combination of therapies. In the spirit of personalized medicine, it will be possible in the future to use the immune cells in the tumour and additional biomarkers to estimate which immunotherapy will work best for each individual patient and what their chances of success are. This is because what happens in the tumor microenvironment between the tumor and immune cells has a dramatic influence on tumor growth and the success of the therapy.

Another important branch of research is concerned with how immunotherapy can be optimally integrated into existing oncological treatments. It is hoped that immunotherapy will be even more effective if it is used in conjunction with other therapies. Our research has shown that acquired resistance to individual drugs can be avoided if immunotherapies with different mechanisms of action are administered simultaneously. The tumor can thus be pushed back more effectively. Immunotherapy can also be given in combination with conventional chemotherapy or radiotherapy. We were able to show that certain chemotherapies stimulate the immune system and can therefore be ideally combined with immunotherapy. Another important combination is the simultaneous administration of immunotherapies with so-called anti-angiogenic substances, i.e. drugs that inhibit the excessive formation of blood vessels in the tumor triggered by the tumor. These tumor's own blood vessels supply the tumor with nutrients and oxygen, but differ from "normal blood vessels" in that they only allow immune system defense cells limited access to the tumor. Initial results show that immunotherapy, when administered simultaneously with these anti-angiogenic substances, achieves significantly better therapeutic success. The immune cells can now reach the tumor cells more easily and destroy them.

Prof. Alfred Zippelius

Co-Chefarzt

Medizinische Onkologie FMH, Mitglied Tumorzentrum, Leiter Labor Tumorimmunologie

Hauttumore, Thoraxtumore, Immuntherapie

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Ovarian cancer

Our research interests focus on gynecological cancers in general and ovarian cancer in particular. (Epithelial) ovarian carcinoma has the highest mortality rate of all gynecological malignancies, as 75 percent of patients are only diagnosed at an advanced stage due to the lack of symptoms. Our research aims to find methods and means to detect this disease as early and reliably as possible and to find the best therapy for each patient in terms of personalized medicine, to better identify risk groups and, last but not least, to find new, more effective and cost-effective forms of therapy. Our research ranges from basic research to transnational and patient-oriented research, including the conduct of clinical trials.

The focus of patient-oriented research is on the evaluation of new therapeutic options and research projects to optimize diagnosis, therapies and surgical processes and to improve the quality management and cost-effectiveness of interventions and treatments: so that each patient can be offered the therapy and treatment that benefits her the most and has a balanced cost-benefit ratio. This research is carried out within the framework of retrospective and prospective multi-center clinical studies, i.e. in collaboration with local, national and international research institutions and hospitals.

One of our focal points is research into the molecular cause(s) of this disease. Although it is now recognized that this is a heterogeneous disease, patients are usually treated with "the standard therapies". Identifying the molecular causes (signatures) of this heterogeneity will help us to find the most optimal, i.e. "tailor-made" therapy or treatment for each patient or group of patients in the future. This also includes finding new and, above all, more reliable methods and indicators, e.g. so-called tumor or biomarkers, for the early detection of this disease. For this research, we benefit from our extensive biobanks with blood and tissue samples from national and international cohorts.

One of our focal points is glycobiology, i.e. we use our specially developed array platforms to investigate the role and function of glycans (sugar molecules) in the development and progression of ovarian cancer and their functions in the immune response, first in cell line models and then in small animal models. These glycans occur in diverse structural variants on practically all proteins and lipids in all cells and perform essential biological functions for the cells. Interestingly, certain glycan structures are only found in carcinoma cells, suggesting that they have a carcinoma-specific function. There is also some evidence that the concentration of antibodies against certain glycan structures, so-called antiglycan antibodies, differs in the blood serum of patients and healthy women: which could mean that certain glycans have tumor or biomarker properties and could even serve as target molecules for immunotherapies, for example. Such antiglycan antibodies are also found in the breast milk of breastfeeding mothers and in urine: the biological function of these antibodies is largely unknown and is also the subject of our research.

Prof. Viola Heinzelmann-Schwarz

Co-Leiterin Frauenklinik

Chefärztin Gynäkologie/Gyn. Onkologie

Further information

Group members
Publications

Studies

Participation in studies

Clinical trials aim to improve the detection and treatment of cancer. They make an important contribution to progress in many very different areas - from early detection and the latest new treatment methods to support measures for patients and relatives (stress management, exercise, etc.).

As a study participant, you can be sure that you will be treated according to the latest scientific findings and under strict, multi-stage quality control. All studies have been reviewed and approved by the Basel Ethics Committee. Participation in studies is generally voluntary.

The University Hospital offers the opportunity to actively participate in clinical trials. If you are interested in participating in a study, please ask your attending physician whether a study is open for your specific disease.

Answers to frequently asked questions regarding participation in clinical trials can be found at the Oncology Department.

For all types of cancer

GO42144 - A Phase Ia/Ib Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-6036 as a Single Agent and in Combination With Other Anti-cancer Therapies in Patients With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation
VARIA / BASKET, Advanced Solid Tumor

TAPISTRY- Tumor-Agnostic Precision Immuno-Oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study.
VARIA / BASKET

Principal Investigator
Raphaël Delaloye
Contact: Raphael.Delaloye@usb.ch

MK-3475-587 - A Multicenter, Open-label, Phase III Extension Trial to Study the Long-term Safety and Efficacy in Participants with Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab Trial
VARIA / BASKET

Principal Investigator
Alfred Zippelius
Contact: Alfred.Zippelius@usb.ch

ANV419-001 - ANV419 Single Agent (Parts A-C) or Combination (Part D) First in Human Study Phase 1/2: Open-label, Dose Escalation and Expansion Study in Patients with Relapsed/Refractory Advanced Solid Tumors
VARIA / BASKET, Advanced Solid Tumor

Principal Investigator
Heinz Läubli
Contact: heinz.laeubli@usb.ch

ON-TRK - Prospective Non-interventional study in patients with locally advanced or metastatic TRK fusion cancer treated with larotrectinib
VARIA / BASKET

DOSe-intensified Image-guidedfractionated stereotactic body radiation therapy for painful spinalmetastases versus conventional radiotherapy: a Randomized Controlled Trial(DOSIS RCT)
VARIA / BASKET, Advanced Solid Tumor, Radiotherapy

Principal Investigator
Prof. Frank Zimmermann
Contact: frank.zimmermann@usb.ch

IOSI-RTO-001 - Stereotactic Radiosurgery or Hypofractionated Image-Guided Radiotherapy to the Surgical Cavity After Resection of Brain Metastases: a Multicenter, Single Arm, Open-label, Phase II Trial
VARIA / BASKET, Radiotherapy, BRAIN TUMORS, Brain Metastases

Principal Investigator
PD Dr. med. Markus Gross
Contact: markus.gross@usb.ch

CA209-8TT - Pan Tumor Nivolumab Rollover Study
VARIA / BASKET, Advanced Solid Tumor

Principal Investigator
Alfred Zippelius
Contact: Alfred.Zippelius@usb.ch

CUPISCO (MX39795) - A phase II, randomized, active-controlled, multi-center study comparing the efficacy and safety of targeted therapy or cancer immunotherapy guided by genomic profiling versus platinum-based chemotherapy in patients with cancer of unknown primary site who have received three cycles of platinum doublet chemotherapy
VARIA / BASKET, CARCINOMA OF UNKNOWN PRIMARY (CUP)

Principal Investigator
Ilker Acemoglu
Contact: IlkerResat.Acemoglu@usb.ch

IOV-COM 202 - A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN-144 or LN-145) in Patients with Solid Tumors
VARIA / BASKET, Advanced Solid Tumor

Principal Investigator
Frank Stenner
Contact: Frank.Stenner@usb.ch

Breast (Breast Center)

POLAR - A phase III open-label, multicenter, randomized trial of adjuvant palbociclib in combination with endocrine therapy versus endocrine therapy alone for patients with hormone receptor positive / HER2-negative resected isolated locoregional recurrence of breast cancer
BREAST CANCER, HR-positive, HER2-negative, 2nd line

Principal Investigator
David Thorn
Contact: praxis.langegasse78@hin.ch

JPCW - eMonarcHER: A Randomized, Double Blind, Placebo-Controlled Phase 3 Study of Abemaciclib Plus Standard Adjuvant Endocrine Therapy in Participants With High-Risk, Node-Positive, HR+, HER2+ Early Breast Cancer Who Have Completed Adjuvant HER2-Targeted Therapy
BREAST CANCER, HR-positive, HER2-positive, ≥ 2nd line

Principal Investigator
Marcus Vetter
Contact: marcus.vetter@usb.ch

DESTINY-Breast12: An Open-Label, Multinational, Multicenter, Phase 3b/4 Study of Trastuzumab Deruxtecan in Patients With or Without Baseline Brain Metastasis With Previously-Treated Advanced/Metastatic HER2-Positive Breast Cancer

Principal Investigator
Christian Kurzeder
Contact: christian.kurzeder@usb.ch

SAKK 23/16: TAXIS - Multicenter phase III study, determination of optimal axillary therapy (surgery vs. radiotherapy) for regional, lymphonodular metastatic breast cancer

Principal Investigator
Walter Weber
Contact: walter.weber@usb.ch

SAKK 96/12 - (REDUSE) - Prevention of Symptomatic Skeletal Events with Denosumab Administered every 4 Weeks versus every 12 Weeks - A Non-Inferiority Phase III Trial
BREAST CANCER, HR-negative, HR-positive, Bone metastases, GENITOURINARY TUMORS, Prostate Cancer, castration resistant

Principal Investigator
Frank Stenner
Contact person: Frank.Stenner@usb.ch

Gastrointestinal (abdominal tumor center)

CA 209-859: A phase 3, randomized, double-blind clinical study of pembro plus chemo vs placebo plus chemo as 1st line treatment in participants with HER2 neg, previously untreated, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma