From single gene analysis to single cell profiling: a new era for precision medicine

Abstract

Molecular profiling of DNA and RNA has provided valuable new insights into the genetic basis of non-malignant and malignant disorders, as well as an increased understanding of basic mechanisms that regulate human disease. Recent technological advances have enabled the analyses of alterations in gene-based structure or function in a comprehensive, high-throughput fashion showing that each tumor type typically exhibits distinct constellations of genetic alterations targeting one or more key cellular pathways that regulate cell growth and proliferation, evasion of the immune system, and other aspects of cancer behavior. These advances have important implications for future research and clinical practice in areas as molecular diagnostics, the implementation of gene or pathwaydirected targeted therapy, and the use of such information to drive drug discovery. The 1st international and 32nd Annual Conference of Italian Association of Cell Cultures (AICC) conference wanted to offer the opportunity to match technological solutions and clinical needs in the era of precision medicine.

KRAS wild-type pancreatic ductal adenocarcinoma: molecular pathology and therapeutic opportunities

“…The genetic hallmarks in this category are represented by the presence of an activated MAPK, of MSI/dMMR, and of kinase-fusion genes in variable proportions. Differently from conventional PDAC, if appropriately selected based on their individual genomic and molecular features, these special PDAC subtypes can be treated with specific therapeutic strategies (see Table 1 for a list of selected ongoing trials with agents targeting molecular aberrations that are enriched in KRAS wild type PDAC), representing an important step towards the establishment of precision oncology for patients with pancreatic cancer [ 71 ]. As exemplified by the recently reported “Know Your Tumor” initiative experience in PDAC [ 72 ], only a minority of patients might currently benefit from extended molecular profiling (46 out of 1223–4% - profiled patients received matched therapy in their experience).…”

Advancing personalized medicine for tuberculosis through the application of immune profiling

“…Each omics discipline has different values different clinical settings. Considering the nature of this infectious disease, which needs the optimal treatment at the earliest timing, immune profiling may be a game-changer in personalized medicine for TB (Di Martino et al, 2020;Wicha et al, 2021). The current approach to confirming TB diagnosis needs drug-susceptibility testing in the form of bacterial culture, and it has a long turnover time for results (Organization, 2020).…”

Association of the OPRM1 A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence

“…The correlational nature of the analyses only allows speculation about causal relationships and needs to be further validated in a longitudinal design. Even though candidate genes as opposed to large-scale GWAS studies have come into disrepute, we believe that there is still a high relevance in connecting single genes and their respective pathways to specific neurocognitive processes and thus providing the opportunity for more specific interventions in precision medicine ( Deb et al, 2010 ; Di Martino et al, 2020 ). Another limitation of our design is that the procedure used here to indicate Pavlovian learning (task phase 4) was not designed to detect between-group effects but instead served to identify subjects who did not learn the Pavlovian contingencies ( Supplemental Information 8 ).…”