In the field of oncology, biomarkers are used to calculate the prognosis of a malignancy, predict suitable treatments, monitor disease progression, and evaluate treatment impact. The range of used biomarkers is extremely wide. Morphological or histological characteristics but also molecular markers on the protein and RNA and DNA level are frequently used. Whereas good markers for the majority of targeted therapies exist, for most tumor entities there is a lack of markers that can be used to predict the response for systemic therapies like chemotherapy. In breast cancer, chemotherapy is predominately used for stage 2–4 disease, being particularly beneficial in estrogen receptor-negative (ER-) disease. Usually, several drugs are given in combinations, and one of the most common treatments is cyclophosphamide plus doxorubicin (Adriamycin®), known as A/C. In general, chemotherapy works by unspecifically destroying fast-growing/fast-replicating cells. In the case of A/C cell death is induced by causing DNA damage during replication. Due to the general mechanism of action for the majority of chemotherapy agents, these drugs next to targeting tumor cells also damage fast-growing normal cells where they cause serious side effects like hair loss or liver and gastrointestinal complications. Although less than 25% of breast cancer patients benefit from chemotherapeutic treatment, this systemic approach is still used as standard care. Because of the severe side effects, it would be highly beneficial to identify markers which can be used to predict the response to chemotherapy preventing treatment of de-novo resistant tumors. In the present invention, we identify SSEA4 (stage-specific embryonic antigen-4), a sialyl-glycolipid, and ST3GAL2, the synthesizing enzyme of SSEA4, as diagnostic and drug response biomarkers in cancer. Expression of SSEA4 and/or ST3GAL2 on/in cancerous cells predicts the outcome for chemotherapeutic treatment of these cells. SSEA4 and/or ST3GAL2 can be used as biomarkers in a method to predict resistance to chemotherapy in an individual with cancer.
SSEA4 AND ST3GAL2 AS CHEMOTHERAPEUTIC DRUG RESPONSE BIOMARKERS
CAIRO, Stefano Enrico;
2015
Abstract
In the field of oncology, biomarkers are used to calculate the prognosis of a malignancy, predict suitable treatments, monitor disease progression, and evaluate treatment impact. The range of used biomarkers is extremely wide. Morphological or histological characteristics but also molecular markers on the protein and RNA and DNA level are frequently used. Whereas good markers for the majority of targeted therapies exist, for most tumor entities there is a lack of markers that can be used to predict the response for systemic therapies like chemotherapy. In breast cancer, chemotherapy is predominately used for stage 2–4 disease, being particularly beneficial in estrogen receptor-negative (ER-) disease. Usually, several drugs are given in combinations, and one of the most common treatments is cyclophosphamide plus doxorubicin (Adriamycin®), known as A/C. In general, chemotherapy works by unspecifically destroying fast-growing/fast-replicating cells. In the case of A/C cell death is induced by causing DNA damage during replication. Due to the general mechanism of action for the majority of chemotherapy agents, these drugs next to targeting tumor cells also damage fast-growing normal cells where they cause serious side effects like hair loss or liver and gastrointestinal complications. Although less than 25% of breast cancer patients benefit from chemotherapeutic treatment, this systemic approach is still used as standard care. Because of the severe side effects, it would be highly beneficial to identify markers which can be used to predict the response to chemotherapy preventing treatment of de-novo resistant tumors. In the present invention, we identify SSEA4 (stage-specific embryonic antigen-4), a sialyl-glycolipid, and ST3GAL2, the synthesizing enzyme of SSEA4, as diagnostic and drug response biomarkers in cancer. Expression of SSEA4 and/or ST3GAL2 on/in cancerous cells predicts the outcome for chemotherapeutic treatment of these cells. SSEA4 and/or ST3GAL2 can be used as biomarkers in a method to predict resistance to chemotherapy in an individual with cancer.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
