Simple SummaryAlternative pre-mRNA splicing is a process that allows for the generation of an extremely diverse proteome from a much smaller number of genes. In this process, non-coding introns are excised from primary mRNA and coding exons are joined together. Different combinations of exons give rise to alternative versions of a protein. Scientists use RNA sequencing methods to study how alternative splicing is deregulated in tumors. Aberrant splicing affects all features of cancer cells: unlimited growth, avoidance of cell death, invasiveness, angiogenesis, and metabolism. Some tumor driving genes, namely, oncogenes, change alternative splicing by influencing molecular pathways that control it. Alternative splicing can also activate genes and pathways that drive tumor growth. Growing knowledge about deregulation of splicing in cancer helps to design better methods of diagnosis and treatment.AbstractThe development of RNA sequencing methods has allowed us to study and better understand the landscape of aberrant pre-mRNA splicing in tumors. Altered splicing patterns are observed in many different tumors and affect all hallmarks of cancer: growth signal independence, avoidance of apoptosis, unlimited proliferation, invasiveness, angiogenesis, and metabolism. In this review, we focus on the interplay between driver oncogenes and alternative splicing in cancer. On one hand, oncogenic proteins—mutant p53, CMYC, KRAS, or PI3K—modify the alternative splicing landscape by regulating expression, phosphorylation, and interaction of splicing factors with spliceosome components. Some splicing factors—SRSF1 and hnRNPA1—are also driver oncogenes. At the same time, aberrant splicing activates key oncogenes and oncogenic pathways: p53 oncogenic isoforms, the RAS-RAF-MAPK pathway, the PI3K-mTOR pathway, the EGF and FGF receptor families, and SRSF1 splicing factor. The ultimate goal of cancer research is a better diagnosis and treatment of cancer patients. In the final part of this review, we discuss present therapeutic opportunities and possible directions of further studies aiming to design therapies targeting alternative splicing mechanisms in the context of driver oncogenes.