Receptor tyrosine kinase inhibitors in cancer.

Targeted therapy is a new cancer treatment approach, involving drugs that particularly target specific proteins in cancer cells, such as receptor tyrosine kinases (RTKs) which are involved in promoting growth and proliferation, Therefore inhibiting these proteins could impede cancer progression. An understanding of RTKs and the relevant signaling cascades, has enabled the development of many targeted drug therapies employing RTK inhibitors (RTKIs) some of which have entered clinical application. Here we discuss RTK structures, activation mechanisms and functions. Moreover, we cover the potential effects of combination drug therapy (including chemotherapy or immunotherapy agents with one RTKI or multiple RTKIs) especially for drug resistant cancers.

Role of the Wnt and GTPase pathways in breast cancer tumorigenesis and treatment.

Breast cancer (BC) is the most frequently diagnosed cancer among women in all the populations of the world. Although the BC mortality rate has declined, resistance to treatment is still a significant challenge for patient survival. Various cellular signaling pathways, such as Wnt and Rho/GTPase have been linked to the development, migration, and metastasis of BC, and also in treatment resistance mechanisms. Some studies have shown an association between two important cellular pathways, Wnt and Rho/GTPase, in cytoskeleton activation and cancer invasion. However, their involvement in BC has received little attention. This review summarizes the Wnt and Rho/GTPases signaling pathway functions, and also the crosstalk between these pathways in the progression, metastasis, and drug resistance mechanisms in BC. Considering the signaling pathways involved in BC tumorigenesis, future studies will need to investigate possible molecular interventions and new opportunities for the development of personalized strategies for BC treatment in order to improve overall outcomes.

The role of endoplasmic reticulum stress in the regulation of long noncoding RNAs in cancer.

Cancer cells must overcome a variety of external and internal stresses to survive and proliferate. These unfavorable conditions include the accumulation of mutations, nutrient deficiency, oxidative stress, and hypoxia. These stresses can cause aggregation of misfolded proteins inside the endoplasmic reticulum. Under these conditions, the cell undergoes endoplasmic reticulum stress (ER-stress), and consequently initiates the unfolded protein response (UPR). Activation of the UPR triggers transcription factors and regulatory factors, including long noncoding RNAs (lncRNAs), which control the gene expression profile to maintain cellular stability and hemostasis. Recent investigations have shown that cancer cells can ensure their survival under adverse conditions by the UPR affecting the expression of lncRNAs. Therefore, understanding the relationship between lncRNA expression and ER stress could open new avenues, and suggest potential therapies to treat various types of cancer.

The potential application of organoids in breast cancer research and treatment.

Tumor heterogeneity is a major challenge for breast cancer researchers who have struggled to find effective treatments despite recent advances in oncology. Although the use of 2D cell culture methods in breast cancer research has been effective, it cannot model the heterogeneity of breast cancer as found within the body. The development of 3D culture of tumor cells and breast cancer organoids has provided a new approach in breast cancer research, allowing the identification of biomarkers, study of the interaction of tumor cells with the microenvironment, and for drug screening and discovery. In addition, the possibility of gene editing in organoids, especially using the CRISPR/Cas9 system, is convenient, and has allowed a more detailed study of tumor behavior in models closer to the physiological condition. The present review covers the application of organoids in breast cancer research. The recent use of gene-editing systems to provide insights into therapeutic approaches for breast cancer, is highlighted. The study of organoids and the possibility of gene manipulation may be a step towards the personalized treatment of breast cancer, which has so far remained unattainable due to the high heterogeneity of breast cancer.

Development of neoantigens: from identification in cancer cells to application in cancer vaccines.

INTRODUCTION: The discovery of neoantigens as mutated proteins specifically expressed in tumor cells but not in normal cells has led to improved cancer vaccines. Targeting neoantigens can induce anti-tumor T-cell responses to destroy tumors without damaging healthy cells. Extensive advances in genome sequencing technology and bioinformatics analysis have made it possible to discover and design effective neoantigens for use in therapeutic cancer vaccines. Neoantigens-based therapeutic personalized vaccines have shown promising results in cancer immunotherapy. AREAS COVERED: We discuss the types of cancer neoantigens that can be recognized by the immune system in this review. We also summarize the detection, identification, and design of neoantigens and their appliction in developing cancer vaccines. Finally, clinical trials of neoantigen-based vaccines, their advantages, and their limitations are reviewed. From 2015 to 2020, the authors conducted a literature search of controlled randomized trials and laboratory investigations that that focused on neoantigens, their use in the design of various types of cancer vaccines. EXPERT OPINION: Neoantigens are cancer cell-specific antigens, which their expression leads to the immune stimulation against tumor cells. The identification and delivery of specific neoantigens to antigen-presenting cells (APCs) with the help of anti-cancer vaccines promise novel and more effective cancer treatments.