Projektinformation
Beskrivning
The proposed project is based on years of successful breast cancer research at Lund University utilizing the unique prospective SCAN-B observational study (PMID:29341157). To date, the SCAN-B study has enrolled >18000 women with primary breast cancer in South Sweden and Uppsala. Through several years of dedicated work we have created truly multi-omic breast cancer cohorts comprising several hundreds of enrolled SCAN-B patients that are population representative and (importantly) has complete clinical data and patient outcome history.
Breast cancer is the most common malignancy in women (approx. 9000 patients/year in Sweden) and a heterogeneous disease at the molecular level. This heterogeneity translates into differences in clinical manifestation, patient therapies, and patient survival. Despite treatment, many women with seemingly less aggressive tumors still relapse, often after several years since the original diagnosis. Similarly, relapse despite aggressive systemic therapy and several years of endocrine therapy (when applicable) is frequent also in women with high-risk disease. Together, this stresses that there is a substantial need for better precision medicine in primary breast cancer, i.e., who and how to treat.
Besides conventional treatment, immune checkpoint inhibition is increasingly being considered in breast cancer, however we are still lacking predictive markers to identify patients that will benefit. With the introduction of neoadjuvant immune checkpoint inhibition in routine management of triple negative breast cancer (TNBC, an aggressive clinical subgroup representing 9% of patients in Sweden today) the importance of the tumor microenvironment (TME) has gained considerable focus (again) in breast cancer, which is often considered as a generally immune cold disease. Whether immune checkpoint inhibition can be used in other subgroups of aggressive breast cancer is now being investigated in ongoing clinical trials (besides other therapeutics like ADCs, CDK4/6 inhibitors etc.). The interaction of tumor cells (based on their somatic alterations) with the host immune system represents a key focus of this proposal.
The proposed project aims to connect already performed massive multi-omics genomic characterization of SCAN-B patients reported as single studies by the main supervisor (e.g. PMID: 31570822, 32719340,33568222,35974007) with ongoing matched in situ characterization of the breast cancer TME using single-plex and multiplex immunohistochemistry (IHC) as well as spatial transcriptomics. The key ambition is to focus on the TME readout of somatic alterations in the tumor cells by linking the “tumor genotype” to the “tissue phenotype” (genotype-phenotype). To achieve this, we need to connect multi-omics data with image data (both representing large scale data types) and ultimately also patient outcome data, requiring new methods and type of analyses – representing a computational challenge.
Breast cancer is the most common malignancy in women (approx. 9000 patients/year in Sweden) and a heterogeneous disease at the molecular level. This heterogeneity translates into differences in clinical manifestation, patient therapies, and patient survival. Despite treatment, many women with seemingly less aggressive tumors still relapse, often after several years since the original diagnosis. Similarly, relapse despite aggressive systemic therapy and several years of endocrine therapy (when applicable) is frequent also in women with high-risk disease. Together, this stresses that there is a substantial need for better precision medicine in primary breast cancer, i.e., who and how to treat.
Besides conventional treatment, immune checkpoint inhibition is increasingly being considered in breast cancer, however we are still lacking predictive markers to identify patients that will benefit. With the introduction of neoadjuvant immune checkpoint inhibition in routine management of triple negative breast cancer (TNBC, an aggressive clinical subgroup representing 9% of patients in Sweden today) the importance of the tumor microenvironment (TME) has gained considerable focus (again) in breast cancer, which is often considered as a generally immune cold disease. Whether immune checkpoint inhibition can be used in other subgroups of aggressive breast cancer is now being investigated in ongoing clinical trials (besides other therapeutics like ADCs, CDK4/6 inhibitors etc.). The interaction of tumor cells (based on their somatic alterations) with the host immune system represents a key focus of this proposal.
The proposed project aims to connect already performed massive multi-omics genomic characterization of SCAN-B patients reported as single studies by the main supervisor (e.g. PMID: 31570822, 32719340,33568222,35974007) with ongoing matched in situ characterization of the breast cancer TME using single-plex and multiplex immunohistochemistry (IHC) as well as spatial transcriptomics. The key ambition is to focus on the TME readout of somatic alterations in the tumor cells by linking the “tumor genotype” to the “tissue phenotype” (genotype-phenotype). To achieve this, we need to connect multi-omics data with image data (both representing large scale data types) and ultimately also patient outcome data, requiring new methods and type of analyses – representing a computational challenge.
| Status | Pågående |
|---|---|
| Gällande start-/slutdatum | 2024/07/01 → 2028/06/30 |
Ämnesklassifikation (UKÄ)
- Bioinformatik och beräkningsbiologi
- Cancer och onkologi