RNA plays a pivotal role in cancer biology, providing valuable insights into the molecular mechanisms underlying cancer development, progression, and treatment. By deciphering the complex interplay between RNA molecules and cancer etiology, researchers can identify novel biomarkers, therapeutic targets, and strategies for improving cancer diagnosis, prognosis, and therapy. RNA found in blood can provide crucial information about the presence and progression of diseases, which has paved the way for utilizing RNA as a biomarker across different cancer stages, from early diagnosis to monitoring treatment responses. All these factors contribute to RNA emerging as a powerful tool in the fight against cancer, offering diagnostic insights and serving as a therapeutic target for innovative therapies.

A remarkable characteristic of RNA as a biomarker is its versatility and specificity to reflect molecular alterations in cancer. Gene expression and regulation aberrate expressions of RNA subtypes, including messenger RNA (mRNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (ciRNA), which can promote or suppress the development of cancer. By evaluating the patterns and levels of specific RNA molecules, researchers, physicians, and clinicians can gain insight into the underlying genetic and molecular tumorigenesis factors, aiding in personalized treatment strategies and informed therapeutic decisions for patients.

How can we exploit mRNA to detect and monitor cancer? mRNA is the primary template used in protein synthesis post gene transcription. mRNA versatility during protein synthesis has revealed distinctive properties for predicting cancer making it an ideal biomarker for different types of cancer. Analyzing the levels of specific mRNA in tumor samples or body fluids (urine and blood) of patients can reveal the characteristics of cancer cells. This is done by comparing the expression of the mRNA between cancerous and non-cancerous tissues or between the stages of cancer, which can provide diagnostic information about cancer.

A variety of mRNA tests has become routinely used for the diagnosis and prognosis of breast cancer. For example, a common hormone receptor (HR+) and human epidermal growth factor receptor positive (HER2+) prognostic test for post-menopausal patients in the early stage of breast cancer is the Prosigna Breast Cancer Assay. It is routinely used in breast cancer diagnosis to assess the activity of 50-gene signatures known as PAM50, based on the four major types of breast cancer. This test has been facilitated by understanding the dynamic nature of mRNA. Other uses of mRNA profiles in cancer diagnosis is in predicting a patient’s response to therapy by continuously monitoring the expression of specific genes related to drug resistance or sensitivity. This will help identify patients who can benefit from available targeted therapies or chemotherapies. For example, mRNA expression patterns in HER2/neu in breast cancer can help predict response to HER2-targeted therapies such as trastuzumab (Herceptin).

Other RNA molecules also provide useful insights in disease progression. A good example is non-coding RNAs (ncRNA), which include miRNAs, lncRNAs, and circRNAs, usually referred to as the dark matter of the genome because their functions are widely unknown. In cancer, ncRNAs have been found to regulate many genes. In some cases, a single ncRNA can regulate several genes while in other cases multiple ncRNAs can regulate a single gene. This complexity of ncRNAs is due to their heterogeneity and limited understanding of their functions in cancer. Ongoing discoveries show that ncRNAs can have both tumor-promoting and tumor-suppressing roles. Besides these capabilities, they can be used in diagnosis, prognosis, as therapy targets, and in monitoring treatment outcomes in cancer patients.

This indicates that discovery and functional investigation of these ncRNAs present a multifaceted role in defining cancer hallmarks by regulating gene expression, signalling pathways, and cellular mechanisms. Therefore, an understanding of the intricate network of ncRNA-mediated interactions is significant in the development of targeted therapies and in improving cancer diagnostics and treatment outcomes.