Projects / Programmes
Prognostic and predictive factors for response in treatment of breast cancer and other cancers
January 1, 2015
- December 31, 2019
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
prognostic factor, predictive factor for response to therapy, breast cancer, renal cell carcinoma, colorectal cancer, diffuse large cell B-cell lymphoma
Researchers (20)
Organisations (3)
Abstract
Current research in oncology is focused primarily on the identification of various prognostic and predictive factors. Prognostic and predictive factors increase the likelihood of personalized management, where each individual cancer patient could receive optimal treatment. Prognostic factors can identify subsets of patients, which need better treatment or management. Furthermore, some molecular prognostic factors can represent potential targets for new anticancer therapies. Predictive factors predict response to a particular type of anticancer therapy.
We aim to study the prognostic role of the tumor-infiltrating lymphocytes (TIL) in women with triple-negative breast cancer (TNBC). Furthermore, its predictive role for the response to chemotherapy will also be studied. Findings of our research might lead to improvement of treatment in women with early TNBC.
Breast cancer in young (( 35 let) women is prognostically less favourable as compared to breast cancer in older patients. Therefore, young women with breast cancer usually undergo more intensive and complex treatment. In this group of patient we aim to study various clinical, histo-pathologic and molecular prognostic factors. We also aim to identify factors, which are associated with infertility after cancer treatment in this vulnerable population of patients.
We oberve that locally-advanced breast cancer (LABC) is quite common among Slovenian women. Due to the advanced stage of the disease the outcome of breast cancer in these women is substantially compromised despite available effective therapies. We aim to identify causative factors, which are associated with the occurence of LABC in Slovenia. Causes for the occurence of LABC in Slobenian women might be in the ineffective diagnostic procedures (in the health system) and/or in women themselves.
In patients with advanced renal cell carcinoma several clinical prognostic factors are available, but currently there are no predictive factors for response to targeted agents available. In patients with advanced renal cell carcinoma we aim to identify predictive molecular factors for response to therapy with mTOR inhibitors.
Although different targeted agents agents are available for treatment of patients with advanced colorectal cancer, most od the patients still succumb to their illness. We aim to determine prognostic role of established and candidate molecular prognostic factors in patients with advanced colorectal cancer.
Rituximab in combination with chemotherapy improves outcome of patients with diffuse large cell B-cell lymphom (DLCBL). We aim to determine whether established prognostic factors retain their prognostic role in patients with DLCBL, who are treated with rituximab. Furthermore, we aim to identify predictive factors for response to rituximab in this group of patients.
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.
Chemotherapy still represents the only option of systemic therapy in women with triple-negative breast cancer (TNBC). Currently, there are no targeted therapies available in this disease. In early TNBC we aim to prevent recurrence of cancer and to cure patients. Unfortunatelly, it is not known which type of chemotherapy (anthracyclines, taxanes, both or platinum agents) and what intensity of chemotherapy (standard treatment or dose-dense treatment) is optimal for an individual patient. Tumor-infiltrating lymphocytes (TIL) can be important prognostic and predictive factor for response to chemotherapy in women with TNBC. For example, women who have strong TIL may have a favourable prognosis and therefore need less intensive or no treatment with chemotherapy. In contrast, those who have weak TIL may have less favourable prognosis and need more intensive treatment with chemotherapy. Furthermore, some cytotoxic agents may be more effective than the others in this group of patients. Personalized approach is also important from the perspective of toxicity as we do not want to cause acute and chronic toxic treatment effects of chemotherapy (toxic damage of heart, secondary leukemia, neuropathy) if not necessary.
Young women with early breast cancer usually need combined therapy as breast cancer is less favourable in this group of patients. However, not all young patients with breast may need intensive treatment. Better understanding of the disese and identification of new prognostic factors may help to identify a subset od patients who need less intensive treatment. Treatment of early breast cancer can cause various long-term toxic effects, icluding impairement of fertility. Treatment-related and other factors, which may be related to impaired fertility after treatment of early breast cancer in Slovenian young patients with breast cancer are not known.
Locally-advanced breast cancer represents an importan burden for health system. Irrespective of treatment that these women receive their outcome is compromised due to the higher stage of the disease. Factors, which are associated with the ocurrence of locally-advanced breast cancer may be specific for Slovenia.
The biggest advancement in treatment of cancer are targeted agents. These drugs are the most effective in cancers with dominant signalling pathways, which are crucial for growth of tumor (e.g. 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. Before the start of therapy with mTOR inhibitors we cannot predict which patients will benefit from these drugs. However, most of patients who receive these drugs develop toxic effects, some life-threatening side effects. Therefore, it is of paramount importance to identify
Significance for the country
Goal of the contemporary oncologic treatment is personalized 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.
Most important scientific results
Annual report
2015,
interim report,
final report
Most important socioeconomically and culturally relevant results
Annual report
2015,
interim report,
final report
