By 2040, the global burden will have grown to 3.2 million new cases per year – a rise of 68% – and is projected to increasingly affect young adults. Approximately 25% of all cases are diagnosed as Stage IV metastatic colorectal carcinoma (mCRC). While there is considerable progress in understanding the diverse biology of cancer and in identifying biomarkers towards some targeted therapies3,4,5, the fact is that, to a high degree, cancer phenotypes are driven by non-genetic mechanisms that present a challenge when deciding the best systemic chemotherapy for an individual patient. 5FU-based combination therapies remain the therapeutic backbone of systemic antineoplastic therapy, but these have not changed much in over 60 years. The majority of mCRC patients are treated with combinations of 5FU, leucovorin and oxaliplatin (FOLFOX), irinotecan (FOLFIRI), the combination of both (FOLFOXIRI), or regorafenib and trifluridine-tipiracil. Colorectal cancer (CRC) is the third most-deadly and fourth most-diagnosed cancer in the world1,2. In 2020, more than 1.9 million new cases and over 930,000 deaths were estimated to have occurred worldwide. Decisive innovation in therapy selection for stage IV mCRC Stage I Stage II Stage III Stage IV 18% 33% 24% approx. 25%
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