Towards clinical trials

The overarching objective of the theme is to advance the field of clinical research by integrating molecular profiling data into trial design and patient selection. By leveraging these molecular insights, researchers aim to identify more effective treatment strategies, optimize patient outcomes, and develop personalized therapeutic approaches. This theme also emphasizes the importance of early detection and understanding germline predisposition to provide comprehensive and tailored care for individuals at risk of cancer.

Coordinating PI: Sirpa Leppä

Liquid biopsy (LB) is a minimally invasive approach, which involves examining cancer-related material, such as circulating tumor DNA (ctDNA) from a blood sample. We have recently demonstrated that 1) pretreatment ctDNA burden is associated with survival in lymphoma patients, and 2) lymphoma-derived ctDNA fragments differ from the other cell-free DNA molecules in their length, which can be utilized to measure minimal residual disease (Fig.1). In some solid cancers, ctDNA analysis can also be used instead of invasive tissue biopsies to inform targeted therapy selection. Along with ctDNA, LBs can be applied to study serum protein profile, which provides additional insights to the crosstalk between the host and tumor.

We will conduct a LB-guided trial, which includes patients with aggressive lymphomas to compare ctDNA guided treatment with standard of care (SOC). Other activities include comprehensive characterization of lymphomas and advanced solid tumors from the LB (both ctDNA and proteome) and tumor tissue, and establishment of LB-based platform for follow-up. Patients’ well-being during therapy is followed using electronic patient reported outcome (ePRO) based follow-up program. We expect to translate our findings into clinical benefit of the patients and better quality of life.

Coordinating PI: Andrea Ganna

Several studies have shown that early signs of cancer can be detected in the blood (“a liquid biopsy”) by studying so-called “cell-free DNA” (cfDNA). The most successful approaches have used methylation information to identify the tissue from which the cancer is originating. In this project, we leverage the power of Helsinki biobank, which has collected plasma samples for >100,000 individuals who broadly consented to scientific research. Because of the large sample size, just by chance, some samples have been collected before a cancer diagnosis. This allows exploring the potential of cfDNA for early cancer detection. We will evaluate if these samples contain sufficient cfDNA.

Coordinating PI: Toni Seppälä

Metastatic colorectal cancer (mCRC) has an extremely poor prognosis if not amenable to surgical management. Every sixth patient presents with synchronously metastatic disease at diagnosis, and another 15% experience metachronous metastatic spread over 2 years after surgery of the primary tumor. The first part of the project focuses our iCAN tissue acquisition efforts to the patients with primarily operable cancer but at the highest risk of metastatic spread, to be ready to guide their oncological management at the time of recurrence. We will ensure that the iCAN basic profiling data of the patients’ primary tumors are ready to be utilized, when needed, and provide an iCAN report of the exomic, transcriptomic, immunologic and pharmacological findings to the multidisciplinary CRC teams (MDT) responsible for the care at the time of oncological decision-making in a practical observational study design. Secondly, a parallel randomized controlled trial of 142 mCRC patients will test the benefits and clinical impact of heavy molecular profiling provided to responsible MDTs or molecular tumor boards. Metastases before and after oncological therapy are tested for tumor evolution, cancer subclone eradication, drug sensitivity and option-modifying genomic vulnerabilities to open alternative lines of therapy

Coordinating PI: Caroline Heckman

Blood diseases such as myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and multiple myeloma (MM) primarily affect older adults and result from acquired genetic changes in blood cells as we age. Several new drugs have been developed, but these are rarely curative and only transiently effective as initially responding patients often relapse. In addition, new drug development is primarily based on information from samples collected at diagnosis, prior to the patient receiving treatment. We hypothesize that tumor cells and the surrounding cells are different when the patient relapses after treatment from cells present when the disease was diagnosed. In this project, we aim to gain new knowledge from blood cancer patient samples taken at different stages of the patient’s disease including before, during and after treatment. The information will help us identify factors within the cancer cell and details about the surrounding cells, especially immune cells, that may affect the response to treatment and that can be leveraged to develop future therapies and treatment strategies. Focusing on relapsed disease, we can identify new targets for drug development and develop methods to predict patient response, which can help guide the next treatment selection.

Coordinating PI: Nina Mars

Much of prognosis research in cancers has focused on tumor-related factors and single high-impact germline variants. As cancer prognostication still remains a major clinical challenge, new avenues of research are warranted. Genome-wide association studies have identified hundreds of germline genetic risk factors impacting the risk of developing cancer, but there is little research on the impact of these factors on cancer prognosis. Building on our prior research on genetic risk factors of common cancers, we will study the impact of common and rare germline genetic variation on cancer prognosis and long-term outcomes. For distinct cancers and across cancers, we explore known and new genetic risk factors alongside previously identified prognostic factors. We study the impact of germline genetic factors on developing multiple primary malignancies, and the interplay between germline genetic factors and tumor-related characteristics and cancer treatments, which are important for understanding long-term health of cancer patients. Providing insight on whether individual-level genetic factors impact cancer outcomes, our results can identify new disease etiology and therapeutic targets, with clinical implications for follow-up of cancer patients and management of long-term risks.

Coordinating PI: Päivi Ojala

Immunotherapy consisting of patient-derived T cells genetically modified to express a tumour-targeting chimeric antigen receptor (CAR) is an innovative and one of the most promising modern approaches for the treatment of cancer. In the CAR-T cell therapy T cells from a patient’s blood are engineered to express tumour specific CARs, followed by cell expansion in culture and re-infusion back into the patient where they mount a tumour-directed immune response upon tumour-associated antigen interaction. CAR-T cell therapy has revolutionized the treatment of blood cancers with remarkable efficacy; however, its application in solid tumours is still limited and faces critical challenges such as cancer heterogeneity, CAR T-cell trafficking into the tumour and immunosuppression in the tumour microenvironment.
The goal of this subproject is to significantly improve the quality of life of patients with cancer. We aim to develop efficient and safe cell therapies to complement the high quality cancer care in Finland. We believe that our research will contribute to shaping the next generation of personalised therapies and thereby to have a significant impact on patient care.