Molecular diagnostics tailoring personalized cancer therapy—an oncologist’s view

Abstract

Medical oncology is rapidly evolving with the implementation of personalized, targeted therapies. Advances in molecular diagnostics and the biologic understanding of cancer pathophysiology led to the identification of specific genetic alterations as drivers of cancer progression. Further, improvements in drug development enable the direct interference with these pathways, which allow tailoring personalized treatments based on a distinct molecular characterization of tumors. Thereby, we are currently experiencing a paradigm-shift in the treatment of cancers towards cancer-type agnostic, molecularly targeted, personalized therapies. However, this concept has several important hurdles and limitations to overcome to ultimately increase the proportion of patients benefitting from the precision oncology approach. These include the assessment of clinical relevancy of identified alterations, capturing and interpreting levels of heterogeneity based on intra-tumoral or time-dependent molecular evolution, and challenges in the practical implementation of precision oncology in routine clinical care. In the present review, we summarize the current state of cancer-agnostic precision oncology, discuss the concept of molecular tumor boards, and consider current limitations of personalized cancer therapy. Further, we provide an outlook towards potential future developments including the implementation of functionality assessments of identified genetic alterations and the broader use of liquid biopsies in order to obtain more comprehensive and longitudinal genetic information that might guide personalized cancer therapy in the future.

Imaging Molecular Targets and Metabolic Pathways in Breast Cancer for Improved Clinical Management: Current Practice and Future Perspectives

“…In the era of precision medicine, the individualization of investigations/therapy by considering clinicopathological and immunohistochemical factors is of utmost importance in treatment decision-making [45]. The NCCN and ESMO guidelines acknowledge that [ 18 F]FDG PET/CT is useful in equivocal cases as well as in identifying unsuspected regional or distant metastases.…”

“…The guidelines are not one-size-fits-all; they should be interpreted in the context of a riskstratified/pre-test probability approach by considering other patient factors. This may reduce the incidence of patients undergoing suboptimal or futile invasive therapies which may result in less-than-ideal results [45]. Although [ 18 F]FDG PET/CT is not advised in stage II breast cancers, unsuspected metastases have been detected on [ 18 F]FDG PET/CT.…”

Chordoma Genetic Aberrations and Targeted Therapies Panorama: A Systematic Literature Review

“…Forrest et al [45] identified INI1 deficiency in pediatric cancers, offering a comprehensive understanding of the genomic and immunologic landscape of INI1-deficient chordomas. This revelation is paramount for tailoring targeted interventions to the unique molecular profiles of individual patients, ushering in an era of precision medicine for chordoma therapy [46]. The study by Forrest et al [45] delves into the intricate genomic and immunologic characterization of INI1-deficient pediatric cancers, unraveling the complexities of this specific subset of chordomas.…”

Cancer Stem Cells from Definition to Detection and Targeted Drugs

“…The insufficient treatment response may be due to the heterogeneity of cancers, which is also associated with CSC biology [2,13]. Thus, the main purpose of stratified medicine is to translate the molecular status of tumour cells into predictive and prognostic indexes that can be applied to personalise treatments leading to longer survival and reduced toxicity [10,14]. In this line, patients who are stratified as high risk for relapse could be treated with adjuvant mode, while patients without detectable CSCs after neoadjuvant treatment and surgery might be adequate for less intensive follow-up procedures.…”