Technological advances in sequencing and molecular imaging are enabling researchers to decode the heterogeneous nature of tumors at the single cell level. As one example, an analysis of transcriptomes of 1,163 tumor samples across 24 cancer types identified 41 different types of mRNA expression patterns that were common among the cancer types tested. Although there were common genes involved in cancer development across different cancer types, researchers found that individual cells within a tumor were highly heterogeneous in terms of the types of mutations they carried (98), which can yield both underlying resistance to therapy as well as distinct vulnerabilities. Understanding and therapeutically targeting tumor heterogeneity is the next frontier in cancer science and medicine. Epithelial-to-mesenchymal Transition Epithelial cells are the cells that tightly connect with each other to form the covering of all body surfaces, line body cavities and hollow organs, and are the major tissue in glands. Roughly 90 percent of cancers develop in epithelial cells (99). Cancers that develop in epithelial cells acquire properties of another type of cells, called mesenchymal cells, which form the connective tissue, blood vessels, and lymphatic tissue, and have the ability to migrate within the body. Cancer cells acquire the mesenchymal characteristic of moving within the body by hijacking pathways fundamental for epithelial-to-mesenchymal cell transition, or EMT, which is an essential process for the formation of organs during normal embryonic development (100). Hijacking of EMT pathways by cancer cells is one of the hallmarks of cancer. Research has established that EMT is regulated by several proteins that promote cancer cell division, survival, and mobility, and enable metastasis (101,102). Recent studies have found that EMT also plays a critical role in the ability of cancer cells to evade the immune system (103). Ongoing research is exploring whether therapeutically targeting EMT could improve clinical outcomes. Tumor Microenvironment Cancer cells interact with and modify surrounding cells and tissues to sustain their ability to multiply unchecked and accumulate in the primary tissue of origin. The cells, molecules, and blood vessels that surround and sustain cancer cells collectively form the tumor microenvironment. The tumor microenvironment can affect how a tumor grows and spreads, and cancer cells can reciprocally influence the tumor microenvironment (see Sidebar 8, p. 33). For instance, cancer cells can release molecules that shape their surrounding environment to provide them with nutrients, oxygen, and a supportive structure. The tumor microenvironment, in turn, can adapt to make it difficult for the immune cells or anticancer drugs to reach and eliminate tumor cells (104,105). The vital role of tumor microenvironment in cancer initiation, progression, and metastasis has made it a key target for therapeutic development. For example, researchers are working to modify certain types of immune cells such that these cells can infiltrate the tumor microenvironment and destroy cancer cells (106) (see Immunotherapy: Pushing the Frontier of Cancer Medicine, p. 99). Blocking the supply of oxygen and nutrients with anticancer therapeutics that inhibit tumor angiogenesis has also shown great promise in therapeutically targeting the tumor microenvironment (106). Cancer Development: Integrating Knowledge We are making remarkable strides toward understanding how cancer develops, grows, and spreads, thanks to contributions of countless researchers across the spectrum of cancer science and medicine. Knowledge gleaned from medical research has already enabled the development of effective anticancer therapies that offer hope to many patients with cancer (see Advancing the Frontiers of Cancer Science and Medicine, p. 68). In parallel, technological advances in our ability to investigate characteristics of cancer cells at single cell and single molecule levels are providing an in-depth knowledge of the complexities of cancer. One of the most important insights gleaned from this knowledge is that each patient’s cancer is unique at the molecular level. Together, these insights have provided the basis for precision medicine, also called personalized medicine. Precision medicine is broadly defined as treating patients based on characteristics that distinguish them from other individuals with the same disease (see Figure 6, p. 36). In cancer, precision medicine means using specific information about a patient’s tumor, such as the genome sequence of cancer cells, to help make a diagnosis, plan treatment, evaluate whether treatment is working, and/ or predict prognosis. In recent years, FDA has approved an increasing number of anticancer therapeutics that are developed on the basis of genomic characteristics, and many molecularly targeted drugs are being used to treat cancers that originate from different organs but share similar genomic characteristics (see Advancing the Frontiers of Cancer Science and Medicine, p. 68) (107,108). The next frontier of precision medicine is to integrate our ever-growing knowledge of the genome, epigenome, proteome, transcriptome, microbiome (see Targeting the Microbiome in Cancer Treatment, p. 150), immune system and other Understanding the Path to Cancer Development AACR Cancer Progress Report 2023 35
RkJQdWJsaXNoZXIy NTkzMzk=