Personalized Medicine: Recent Progress in Cancer Therapy

Abstract

Translational research has revolutionized how we develop new treatments for cancer patients. The change from an organ-centric concept guiding treatment choice towards deep molecular analysis, driving a personalized approach, is one of the most important advances of modern oncology. Several tools such as next generation sequencing and RNA sequencing have greatly improved the capacity to detect predictive and prognostic molecular alterations. Detection of gene mutations, amplifications, and fusions has therefore altered the history of several diseases in both a localized and metastatic setting. This shift in perspective, in which attention is focused on the specific molecular alterations of the tumor, has opened the door to personalized treatment. This situation is reflected in the increasing number of basket trials selecting specific molecular targets. Nonetheless, some weaknesses need to be addressed. The complexity of cancer cells enriched with concomitant molecular alterations complicates identification of the driver. Moreover, tumor heterogeneity could be responsible for the lack of benefit when targeted agents are used. In light of this, there is growing interest in the role of multidisciplinary committees or molecular tumor boards to try to enhance selection. The aim of this review is to critically analyze the evolution of cancer treatment towards a precision approach, underlining some recent successes and unexpected failures.

Three-Dimensional Culture Systems in Gastric Cancer Research

“…Treatment with lapatinib, a tyrosine kinase inhibitor that targets the EGFR and HER2 tyrosine kinases, was effective against ErbB2-amplified PDTO compared to wild-type PDTO [ 138 ]. The evolution of translational research, through its applications with PDTO models, makes it emerge as a crucial strategy in personalized medicine programs [ 131 , 158 ]. New clinical trials are required to further validate the benefits of GC PDTO in personalized medicine, i.e., assessing the correlation between the in vivo primary tumor response and the ex vivo drug-mediated cytotoxicity.…”

Precision Medicine to Treat Advanced Gastroesophageal Adenocarcinoma: A Work in Progress

“…All these receptors are activated by FGF, and participate in cell survival and proliferation [ 78 , 79 ]. Multiple trials studying diverse solid tumors have proposed the aberrant FGFR signaling pathway as a potential therapeutic target, and several inhibitors are under development ( Table 4 ) [ 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ]. The FGFR2 splice variant FGFR2b [ 89 ] is overexpressed in 2.5–31.1% of GEA [ 10 ].…”

Next Generation Sequencing in Cytopathology: Focus on Non-Small Cell Lung Cancer

“…In the current era of precision medicine, the validation of several predictive biomarkers has dramatically improved the clinical outcomes of advanced cancer patients. For instance, unlike conventional radio-chemotherapeutic agents, tyrosine kinase inhibitors (TKIs) are therapeutically advantageous not only in improving overall patients' survival but also in reducing treatment-associated toxicities ( 1 ). However, the molecular heterogeneity of many tumors oftentimes renders some patients unresponsive to these types of treatments.…”