Next-Generation Novel Noninvasive Cancer Molecular Diagnostics Platforms Beyond Tissues

In recent years, there has been a revolutionary expansion in technologic advances and therapeutic innovations in cancer medicine. Cancer diagnostics has begun to move away from a sole dependence on direct tumor tissue biopsy for cancer detection, diagnosis, and treatment monitoring. The need for improvement in molecular cancer diagnostics has never been more important, with not only the advent of cancer genomics and genomics-guided precision medicine but also the recent arrival of cancer immunotherapies. Owing to the practical limitations and risks associated with tissue-based biopsy diagnostics, novel noninvasive cancer diagnostics platforms have continued to evolve and expand in recent years. Examples of these platforms include the liquid biopsy, which is used to interrogate ctDNA or circulating tumor cells, proteomics, metabolomics, and exosomes; the urine biopsy, which is used to assay ctDNAs; saliva and stool biopsies, which are used for molecular genomics assays; and the breath biopsy, which measures volatile organic compounds. These next-generation noninvasive molecular diagnostics assays beyond tissues fundamentally transform the potential utilities of cancer diagnostics to enable repeat, prospective, and serial longitudinal "biopsies" to monitor disease response resistance and progression on therapies. Moreover, they allow continual interrogation and molecular in-depth analysis of the evolving tumor's pan-canceromics under therapeutic stress. These technological and diagnostic advances have already brought about paradigm-changing next-generation cancer therapeutic strategies to enhance overall treatment efficacies. This article reviews the key noninvasive next-generation molecular diagnostics platforms beyond tissues, with emphasis on clinical utilities and applications.