Projects / Programmes
Prognostic and predictive factors for response in treatment of different types of cancer
January 1, 2020
- December 31, 2027
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B007 |
Biomedical sciences |
Medicine (human and vertebrates) |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
sequencing of the new generation, liquide biopsy, predictive and prognostic factors, predictive response factor for treatment, different types of cancer
Data for the last 5 years (citations for the last 10 years) on
June 25, 2024;
A3 for period
2018-2022
| Database |
Linked records |
Citations |
Pure citations |
Average pure citations |
| WoS |
677 |
17,881 |
17,323 |
25.59 |
| Scopus |
563 |
20,513 |
19,926 |
35.39 |
Researchers (25)
Organisations (3)
Abstract
At the Institute of Oncology Ljubljana are treated patients with different types of tumors, using also the new treatment modalities, including targeted drugs and immunotherapy. This research program will continue to explore already established and develop new prognostic and predictive factors that can predict the response to the treatment. This will help us in finding the best personalized approach to every patient and offer the optimal treatment to each individual cancer patient. Knowing the biomarkers status in patients with various cancers can give us information about the course of the disease and the response to the treatment. Early discovery of a disease recidive or progression enables oncologists for early treatment and therapeutic strategy change when we can catch the disease while in a smaller scale and the patient in a better condition. Consequently a longer survival of the patient will be achieved.
For this aim, genetic analyzes of cancerous tissue and / or body liquids assessed with next generation sequencing will be incorporated. Sequencing of target genes can determine various genetic changes or mutations, and change of the molecular profile of the disease in the course of the treatment or in the case of disease progression. Different gene mutations are more typical for certain cancers and their treatment, and they also show the different organic affinity of cancer cells for breeding. The next generation sequencing is a new tool, already validated and highly sensitive to detect the changes in the dynamics of the disease or changes in the molecular profile of the disease very early and can provide data for the simultaneous detection and identification of fusions, point mutations, and the expression level of more than hundred genes specific to different cancers. Here we will develop some new potential biomarkers that can predict the affinity of the cancer cells for breading, like the presence of gene mutations for Tropomyosin receptor kinase (NTRK1, NTRK2, NTRK3) that indicate affinity for the brain, with a poor prognosis or high expression of interferon alpha (IFN) genes, assessed by Interferon Gamma Messenger RNA Signature, that can be a predictive factor for a better response to immunotherapy (PD1 / PDL1 inhibitors).
New knowledge and new tumor biomarkers will be eventually implemented in treatment of cancer patients in Slovenia.
Significance for science
Due to better understanding of the biology of cancer many new effective anticancer agents were approved in recent years. In oncology we strive for the personalized approach. With this approach we aim to treat every individual cancer patient with the most effective and at the same time the least toxic therapy. To reach this goal it is important to know prognostic factors and predictive factors for response to a particular anticancer therapy. Furthermore, it is also important to understand predictive factors for for the development of early and late toxic effects related to anticancer treatment.
The biggest advancement in treatment of cancer are targeted agents and the immunotherapy. These drugs are the most effective in cancers with dominant signalling pathways, which are crucial for growth of tumor (e.g. cetuximab targeting EGFR in EGFR positive metastatic colorectal cancer, trastuzumab targeting HER-2 in HER-2 positive breast cancer, imatinib targeting Bcr-Abl fusion protein in chronic myeloic leukemia or gefitinib targeting the activating mutation of EGFR in non-small cell lung cancer). In these cancers biomarkers are available, which predict response to these agents. Unfortunatelly, not all targeted agents are like this. Although they are called targeted agents for many of them actually we do not know the corresponding targets within cancer cells or they are targeting pathways which are not dominant. Consequently, there are no predictive biomarkers available for them. An examplele of such drugs are mTOR inhibitors, which are used for treatment of patients with advanced renal cell carcinoma or VEGF inhibitors used in advanced colorectal cancer. Before the start of therapy with mTOR or VEGF inhibitors we cannot predict which patients will benefit from these drugs. However, most of the patients who receive these drugs develop toxic effects, some life-threatening side effects.Therefore, it is of paramount importance to identify predictive biomarkers for response to these and other similar drugs.
We also need to identify new prognostic biomarkers (e.g. NTRK1, NTRK2, NTRK3 ), which could potentially serve as targets for the development of new and more effective therapies, and in the same time can predict the cancer cells breeding afinity for different organs, esspecially for the CNS. Interferon Gamma Messenger RNA Signature is a predictive factor for a better response to immunotherapy (PD1 / PDL1 inhibitors). Increased intensity of interferon alpha (IFN) genes can be determined by IFN signature - Interferon Gamma Messenger RNA Signature.
Early discovery of a disease recidive or progression enables oncologists for early treatment and therapeutic strategy change when we can catch the disease while in a smaller scale and the patient in a better condition. Consequently a longer survival of the patient should be acchieved. Genetic analyzes of cancerous tissue and / or body liquids with the next generation sequencing, can predict changes in the dynamics of the disease or changes in the molecular profile of the disease very early. The burden of circulating tumor DNA (cDNA) is an early negative predictive factor. Sequencing of target genes can determine various genetic changes or mutations, and change of the molecular profile of the disease in the course of treatment or in the case of disease progression. Different gene mutations are more typical for certain cancers and their treatment, and they also show the different organic affinity of cancer cells for breeding.
Significance for the country
The goal of the contemporary oncologic treatment is thepersonalized approach, which allows every individual patient the most effective and at the same time the least toxic treatment. With better understanding of prognostic and predictive factors we can further improve currently available personalized approach. In an individual patient we aim to improve a chance of cure and to minimize acute and chronic toxic effects of therapy. A higher proportion of cured patients who experience minimal late side effects of treatment could contribute to increased power of our State.
Not only an individual but the whole community can benefit by this approach. The average monthly cost of new anticancer systemic therapies for an individual patient is several thousand of euros. However, many patients who are treated with these new agents do not benefit from them. In current situation of the economic crisis costs of anticancer treatment are becoming unsustainable. With better tailored personalized treatment approach we could substantially decrease the costs of oncologic treatment.
Results of our studies will be published in international journals and presented at interanational scientific meetings, which can increase the visibility of Slovenia around the world. Our research studies will enable even more intensive integration of Slovenian researchers into the interantional scientific community. In Slovenia, our research program will contribute fo a faster introduction of modern methods in routine practice and to improved professional quality. During program implementation we will ensure education and training of students and other people in training.
