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TARgeted Gynaecologic ONcology (TARGON)

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​​​​​​​​​​The University Medical Center Groningen (UMCG) is the tertiary referral center for the North-east of the Netherlands (catchment area ca. 3.5 million people). Within the UMCG longstanding bilateral collaborations have been established on improving prevention, early diagnosis and treatment strategies in patients with premalignant and malignant gynecologic neoplasia. In the TARGON program of the Cancer Research Center Groningen, these collaborations have been broadened and intensified by bringing together gynecologic oncologists, medical oncologists, radiotherapists, clinical geneticists, epidemiologists, psychologists, sexologists, pathologists, biologists, pharmacists, nuclear medicine specialists and immunologists.

The main focus of TARGON is the translation of basic and preclinical research to clinically relevant settings by taking advantage of our large number of referrals of patients with pre-malignant and malignant gynecologic neoplasia and our unique databases consisting of clinical, genetic and pathological characteristics of the majority of patients treated at the UMCG. The gained knowledge within the program not only stimulates basic research but also translational and clinical research, thus enabling research from bed-to-bench and the reverse.

Mission  

The mission of the programme TARGON is to promote, integrate and optimize excellent basic, translational and clinical research that has an impact on overall survival and quality of life in patients with (pre)malignant gynecologic neoplasia.

Programme Leaders   Principal Investigators   Description of the Programme  

The main focus of TARGON is the translation of basic and preclinical research to clinically relevant settings by taking advantage of our large number of referrals of patients with pre-malignant and malignant gynecologic neoplasia and our unique databases consisting of clinical, genetic and pathological characteristics of the majority of patients treated at the UMCG. The gained knowledge within the programme not only stimulates basic research but also translational and clinical research, thus enabling research from bed-to-bench and the reverse.

To intensify these collaborations while maintaining the scope of the research, specific areas are emphasized in existing collaborations regarding the various patient categories and tumor (sub)types:

1. Regarding hereditary cancers the primary focus is on ovarian and breast cancer (BRCA1 & BRCA2 mutation carriers) and endometrial cancers in women with Lynch syndrome. Research includes establishing preclinical disease models, identification of risk modifiers and targets for treatment, and the development of strategies to target and prevent hereditary tumors. Research findings can be immediately applied in genetic counseling and for prevention and treatment strategies in the large population that is referred to and screened in the participating departments at the UMCG.

2. Cervical cancer is the primary focus for research on (i) prevention and early diagnosis (e.g. using DNA methylation markers) and development new treatment strategies including (ii) therapeutic vaccination strategies. Additional to (i): specific and sensitive methylation markers are investigated by means of several genome-wide approaches, resulting in the identification of a methylation panel of genes; these could improve population-based cervical cancer screening. The role of these genes in cervical carcinogenesis is also analyzed to identify novel targets for treatment. Additional to (ii): innovative immunization strategies are being developed against HPV-induced neoplasia (e.g. cervical intraepithelial neoplasia (CIN) and cervical cancer). Several approaches related to the activation of the innate and adaptive immune system are being pursued, including genetic immunization with recombinant suicide viral vectors based on Semliki Forest virus and protein/virosome-based immunization strategies. For valorization of this strategy, a company (VICINIVAX - vicinivax.com) has been founded, a spin-off from the University Medical Center Groningen.

3. Multimodality treatments are being explored to improve anti-cancer treatment, e.g. in ovarian cancer histological-subtypes. The multimodality treatments are based on tumor characteristics of chemo-resistant ovarian cancer, derived from transcriptome, kinome, methylome and immune profiles to target pathways related to apoptosis, survival, oncogene activation and DNA methylation, as well as enhancing anti-tumor activity of the immune cells. Efficacy of treatments is tested in cell lines and xenograft models, ex-vivo patient living explants, and in-vivo patient derived xenotransplants in mice. These patient-derived models are essential to study the interactions between tumor cells and microenvironment, including immune cells.

4. Clinical research focus on exploring novel anticancer therapies and surgeon assisting technologies for sensitive detection of local and distant metastases in cervical, endometrial, ovarian and vulvar cancer. Imaging guided development of novel anticancer therapies and the detection of sentinel nodes (e.g. vulvar cancer) or metastases (e.g. ovarian cancer) are extensively explored. Therapeutic cancer vaccination clinical trials are in development and will be added to the multimodality treatment strategies.

Relevance to Healthy Ageing  

Healthy Ageing is the focal theme of both the UMCG and University of Groningen. In recent years strong initiatives have been undertaken by the UMCG organization to profile and implement this theme. For the CRCG, Healthy Ageing can be formulated as “healthier and longer lives of cancer patients through improved care”.

Cancer is the most important cause of death in the Netherlands. Improved prevention and early detection of gynecologic cancers will have a major impact on healthy ageing of women. With the development of preventive and novel treatment strategies using innovative preclinical models, the TARGON program will reduce overall cancer-related mortality and short-term and long-term morbidity induced by the current treatments. TARGON focuses on extensive collaborations with the ERIBA and OncoLifeS programs to further contribute to the healthy aging programme.

Finally, the Healthy Ageing program of the CRCG is consistent with the recent decision of the UMCG to establish a Comprehensive Cancer Center (CCC). The CCC will offer cancer patients a fully integrated care package in which patient care will be embedded in a streamlined care program. The management of the CCC will be responsible for the total care program. Among the PIs of TARGON, several medical oncologists, gynecologic oncologists, and pathologists are clinically involved in the CCC. This will ensure close collaboration between CCC and CRCG in order to implement a stronger interaction between patient care and TARGON.

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