Cancer Biomarker Discovery and Therapeutic Targeting

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Breast cancer (BC) is the most common cancer type in females worldwide. Despite numerous advances made in the field, BC remains the most common cancer among women, accounting for the highest number of cancer-related mortalities in women. The molecular mechanisms involved in BC pathogenesis have been thoroughly studied, leading to BC classification into three major subtypes. Among those, triple-negative breast cancer (TNBC) represents 15% to 20% of invasive breast cancers and is characterized by the lack of expression of estrogen receptors (ER), progesterone receptors (PR), and lack of amplification of human epidermal growth factor receptor 2 (HER2). TNBC has been shown to particularly affect women younger in age, and tumors tend to be larger in size, with higher metastasis, relapse frequencies, poorer prognosis, and relatively worse outcome in patients. With the lack of available known targets in TNBC, patients generally do not benefit from endocrine therapy; therefore, surgery, radiotherapy, and chemotherapy remain the primary mode of treatment. Cumulative evidence suggests added benefit for neoadjuvant chemotherapy (NAC) in a subset of triple negative breast cancer (TNBC) patients, however, the exact molecular signature predictive of response to NAC remains to be elucidated.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been identified in recent years to be important players in multiple biological systems, mainly through gene regulation. Differential expression of some miRNAs and lncRNAs have been associated with several types of disease, including cancer. The team’s recent work has identified the lncRNA transcriptional landscape and classified BC into different molecular subtypes, employing lncRNA transcriptome data. The current focus of this research group is to better understand TNBC at the molecular and cellular levels and to identify novel diagnostics and prognostic biomarkers associated with TNBC resistance to cancer chemotherapy, with main emphasis on microRNA (miRNA) and lncRNA employing CRISPR-Cas9 and other state-of-the-art technologies.

Latest Publications

  • Shaath H, Vishnubalaji R, Elkord E, Alajez NM. Cells. Single-Cell Transcriptome Analysis Highlights a Role for Neutrophils and Inflammatory Macrophages in the Pathogenesis of Severe COVID-19. Cells. 2020 Oct 29;9(11):E2374.
  • Elango R, Alsaleh KA, Vishnubalaji R, Manikandan M, Ali AM, Abd El-Aziz N, Altheyab A, Al-Rikabi A, Alfayez M, Aldahmash A, Alajez NM. MicroRNA Expression Profiling on Paired Primary and Lymph Node Metastatic Breast Cancer Revealed Distinct microRNA Profile Associated With LNM. Front Oncol. 2020 May 19;10:756.
  • Vishnubalaji R, Shaath H, Elango R, Alajez NM. Noncoding RNAs as potential mediators of resistance to cancer immunotherapy. Semin Cancer Biol. 2020 Oct;65:65-79.
  • 4. Vishnubalaji R, Shaath H, Elkord E, Alajez NM. Long non-coding RNA (lncRNA) transcriptional landscape in breast cancer identifies LINC01614 as non-favorable prognostic biomarker regulated by TGFβ and focal adhesion kinase (FAK) signaling. Cell Death Discov. 2019 Jun 24;5:109.
  • Hamam R, Ali AM, Alsaleh KA, Kassem M, Alfayez M, Aldahmash A, Alajez NM. MicroRNA expression profiling on individual breast cancer patients identifies novel panel of circulating microRNA for early detection. Sci Rep. 2016 May 16;6:25997.
  • Alajez NM, Schmielau J, Alter MD, Cascio M, Finn OJ. Therapeutic potential of a tumor-specific, MHC-unrestricted T-cell receptor expressed on effector cells of the innate and the adaptive immune system through bone marrow transduction and immune reconstitution. Blood. 2005 Jun 15;105(12):4583-9.