76 The landscape of precision oncology has seen remarkable growth over the past five years, according to a recent study conducted by researchers at the Memorial Sloan Kettering Cancer Center. The study, published in Cancer Discovery, highlights the significant expansion of clinical actionability, leading to improved treatment outcomes for cancer patients. The study, which was led by Sarah P. Suehnholz and her team, looked at 47,271 solid tumour samples sequenced with the MSK-IMPACT clinical assay to measure the growth of clinical actionability. Researchers looked at two versions of the OncoKB knowledge base from 2017 and 2022 and saw that the percentage of tumours that had biomarkers that could predict how well a treatment would work went from 8.9% to 31.6%. Simultaneously, the proportion of tumours with non-actionable drivers nearly halved, dropping from 44.2% to 22.8%. This expansion is attributed to several FDA approvals of new cancer drugs targeting specific genetic mutations. For instance, alpelisib was approved for PIK3CA-mutant breast cancer, erdafitinib for FGFR3-mutant bladder cancer, and sotorasib for KRAS-G12C-mutant non-small cell lung cancer (NSCLC) . The approvals have made a big difference in the number of people who can get precision oncology treatments. For NSCLC alone, the percentage of tumour samples with a level 1 biomarker that can predict therapy response has gone up by 12 percentage points. Notably, the study shows the effects of tumor-agnostic drug approvals, which have made it easier for people with rare or unknown primary cancer subtypes to get precision therapies. Among the 1,423 cancers of unknown primary origin, 21.4% became eligible for FDA-approved precision oncology therapies for the first time during the five-year period. This includes drugs like larotrectinib for NTRK-fusion-positive tumours, which had a significant impact on salivary gland cancer, increasing the fraction of tumours classified as level 1 by 5.7 percentage points . Despite the advancements, the study highlights ongoing challenges and unmet needs in the field of precision oncology. One big problem is how to treat cancers that are caused by oncogenic drivers that can not be figured out yet, like TP53, KRAS, and CDKN2A. These are the genes that are most often changed in tumours and can not be changed clinically. The researchers emphasise the need for innovative therapeutic strategies to target these alterations and improve patient outcomes further. Additionally, the study points out the disparities in access to precision oncology therapies, particularly in countries outside the United States. While the U.S., France, and Canada have reported higher rates of patients matched to precision oncology trials, countries like Singapore have significantly lower match rates, highlighting the need for global efforts to improve access to these treatments . To deal with these problems, the study calls for the creation of targeted therapies that are more selective and less harmful that can be used together to get the most out of precision oncology-based strategies. Furthermore, novel diagnostic platforms such as whole-genome and whole-transcriptome sequencing, proteomics, and spatial-omics technologies are expected to play a crucial role in the more targeted use of these therapies in the future . The researchers come to the conclusion that even though a lot of progress has been made in making precision oncology-based treatment paradigms more widely available, there is still a need for new therapeutic strategies, especially for cancers that do not have oncogenic drivers that can be found yet. They call for ongoing research and development efforts to address these challenges and ensure that more patients can benefit from the advancements in precision oncology .