# From Genomics to AI: Revolutionizing Precision Medicine in Oncology
## 4 Genomics in Cancer Treatment  
### Targeted Therapies  
The rapid progress in genomic technologies has fundamentally transformed cancer treatment by facilitating the development of highly specific therapies that target genetic variants driving tumor growth. These targeted therapies are designed to interfere with specific molecular targets involved in cancer development, offering the advantage of precision over traditional treatments, like chemotherapy, which affects both healthy and malignant cells indiscriminately [45].  
One of the key advances in the field is the ability to map tumor pathogenic variants through genomic profiling by identifying specific alterations that can be targeted by drugs. For example, _EGFR_ pathogenic variants are commonly found in non-small cell lung cancer (NSCLC) and led to the development of EGFR inhibitors, such as erlotinib and osimer-tinib, which directly target and block the mutated EGFR receptor, preventing cancer cell growth and survival [46]. This approach has shown significant improvements in patient outcomes, particularly for those with these specific mutations, compared to traditional chemotherapy (Figure 2).  
Similarly, PARP inhibitors, such as olaparib, represent a promising class of drugs for treating cancers with _BRCA1/2_ variants, notably in breast and ovarian cancers [36; 37]. These variants impair the DNA repair mechanism in cancer cells, and PARP inhibitors exploit this vulnerability by preventing further DNA repair, leading to cancer cell death.  
The use of NGS has also allowed for the identification of other pathogenic variants in cancers, such as _ALK_ and _ROS1_ variants in lung cancer, which can be targeted by drugs like crizotinib and alectinib [47]. These variants typically involve gene fusions that result in the constitutive activation of the ALK kinase domain, leading to uncontrolled cell signaling, proliferation, and survival in cancer cells. These findings underscore the importance of  
Figure 2: Erlotinib mechanism of action in non-small cell lung cancer (NSCLC). **(A)** Untreated cancer cell: In NSCLC, activating _EGFR_ mutations (e.g., Exon 19 deletion or Exon 21 L858R point mutation) leads to constitutively active EGFR, driving uncontrolled downstream signaling through pathways like PI3K/AKT/mTOR. This promotes increased cell proliferation, survival, angiogenesis, and tumorigenesis. **(B)** Treated cancer cell: Erlotinib, a tyrosine kinase inhibitor, specifically binds to and inhibits the mutated EGFR. This blocks downstream signaling, resulting in reduced cell proliferation and increased apoptosis, offering a personalized treatment for patients with these specific alterations.  
genomics in personalizing treatment, as therapies can now be tailored to specific genetic alterations within a tumor.  
By identifying and targeting driver variants within the cancer genome, targeted therapies allow for more effective treatments with fewer side effects compared to traditional therapies, improving the overall quality of life of cancer patients. Table 3 summarizes key oncogenes, their associated cancer types, the functional consequence of their mutations, and currently available targeted therapies.