In this review we aim to summarize studies investigating the impact of a molecular profiling (MP)-guided treatment approach in heavily pretreated cancer patients. In summary, many independent single- and multicenter studies showed a significant benefit of MP-guided treatment regarding response rates and survival. However, in the only randomized trial conducted so far, no benefit of MP-guided targeted therapy was observed. Notably, various profiling approaches were conducted in the respective studies: some studies used a single analytic approach (i.e. next-generation sequencing), others applied multiple analytic methods to perform comprehensive molecular profiling. It seems that multiplatform profiling analyses, detected an increased number of druggable molecular targets or signaling pathway alterations and that a higher proportion of patients was treated according to the molecular cancer profile. Even though no randomized study has shown a benefit of molecular profiling so far, many studies indicate that MP-guided treatment can be beneficial in patients with relapsed and/or refractory cancer. Currently ongoing large randomized trials (i.e. NCI-MATCH, TAPUR) will add evidence to the role of profiling-guided cancer treatment.
Keywords: ASCO, American Society of Clinical Oncology; Abl, Abelson murine leukemia viral oncogene homolog 1; Bcr, Breakpoint cluster region; CGH, Comparative genomic hybridization; CISH, Chromogenic in-situ hybridization; CR, Complete response; DNA, Deoxyribonucleic acid; FDA, Food and Drug Administration; FGFR, Fibroblast growth factor receptor; FISH, Fluorescence in-situ hybridization; HER2, Human epidermal growth factor receptor 2; HR, Hazard Ratio; IHC, Immunohistochemistry; MEK, Mitogen-activated protein kinase; MP, Molecular profile; MSI, Microsatellite Instability; Metastatic cancer; Molecular profiling; NCI, National Cancer Institute; NGS, Next generation sequencing; ORR, Overall response rate; OS, Overall Survival; PCR, Polymerase chain reaction; PFS, Progression-free survival; PIK3CA, Phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit alpha; PR, Partial Response; PTEN, Phosphatase and tensin homolog; Personalized medicine; Precision oncology; R/R, Refractory/Relapsed; RAF, Rapidly growing fibrosarcoma - protein; RNA, Ribonucleic acid; SD, Stable Disease; TTF, Time to treatment failure; WES, Whole-exome sequencing; mTOR, Mammalian target of Rapamycin.