Proteomic analysis identifies signatures associated w/ survival in breast cancer patients

The cover for issue 17 of @Oncotarget features Figure 8, "Survival probability according to the expression of IGF1R mRNA and an additional gene," by Sinai-Livne, et al.

READ MORE: While this paradigm is based on well-established biological facts, including the potent anti-apoptotic and cell survival capabilities of the receptor, most Phase III clinical trials designed to target the IGF1R led to disappointing results.

Of clinical relevance, these analyses indicate that high IGF1R baseline expression may serve as a predictive biomarker for IGF1R targeted therapy.

Dr. Haim Werner from The Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine as well as The Yoran Institute for Human Genome Research at Tel Aviv University said, "Breast cancer is the most frequently diagnosed cancer worldwide."

"Breast cancer is the most frequently diagnosed cancer worldwide."

- Dr. Haim Werner, The Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine & The Yoran Institute for Human Genome Research at Tel Aviv University

According to the World Health Organization, breast cancer accounts for 25% of all female cancers and 12% of all cancers.

The IGF system has an important role in the development and maturation of the mammary gland as well as in breast cancer initiation and progression.

Extensive molecular profiling revealed that a number of components of the IGF signaling pathway, including insulin receptor substrate-2 and IGF-binding protein-5 among others, play key roles in determining the sensitivity of cancer cells to a humanized IGF1R antibody.

The present study was aimed at:

1. Evaluating the efficacy of IGF1R inhibition as monotherapy in comparison to combination treatment with chemotherapy in breast cancer cells;
2. Assessing the potential synergism achieved by combination therapy; and,
3. Characterizing this combined approach from a proteomic/bioinformatics perspective.

Figure 8: Survival probability according to the expression of IGF1R mRNA and an additional gene. Patients expressing low (LOW1) or high (HIGH1) levels of IGF1R and FBLN1 (A), TACC3 (B), PDCD4 (C), or SART1 (D). Patients with high levels of the second gene are denoted HIGH2 and patients with low levels of the second gene are denoted LOW2.

In addition, public databases of breast cancer patients were analyzed in order to address the impact of IGF1R expression on survival and to identify potential signatures associated with improved survival.

The Werner Research Team concluded in their Oncotarget Research Paper, "our study provides evidence that co-treatment of IGF1R inhibitor along with chemotherapeutic drugs greatly improves the treatment efficiency in breast cancer cells expressing a high level of IGF1R. Data suggest that high IGF1R baseline expression may serve as a predictive biomarker for IGF1R targeted therapy. While many clinical trials conducted in recent years have shown that IGF1R-directed monotherapy is a poor therapeutic approach, we show that combining this therapy with chemotherapy leads to a potent synergistic effect. Bioinformatics analyses shed light on some of the biological pathways that might be responsible for this synergy. Finally, corroborating the results in the clinical setting may be a step towards personalized oncological treatments."

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DOI - https://doi.org/10.18632/oncotarget.27566

Full text - https://www.oncotarget.com/article/27566/text/

Correspondence to - Haim Werner - hwerner@post.tau.ac.il

Keywords - insulin-like growth factor-1 (IGF1), IGF1 receptor (IGF1R), targeted therapy, breast cancer, proteomic analysis

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