Targeted approaches for HER2 breast cancer therapy: News from nanomedicine?

About 30% of human breast cancers are human epidermal growth factor receptor 2 （HER2）＋. This particular biological portrait is characterized by the overexpression of HER2 receptor with the subsequent deregulation of downstream pathways, which control cellular survival and proliferation. The most effective treatment for HER2＋ cancer is represented by therapy with HER2-targeted agents. Anti-HER2 therapy dramatically improves clini-cal outcomes, although it shows some limitations in achieving a proper treatment. These drawbacks of HER2-targeted therapy may be overcome with the develop-ment of HER2-targeted drug delivery nanodevices. These nanoparticles possess an internal three-dimensional com-partimentalization, which allows to combine the specifc target recognition with their capability to act as a drug reservoir for the selective delivery of chemotherapics to tumor sites. Moreover, nanoparticles useful in photo-thermal ablation or in photodynamic therapy have been functionalized in order to match specifcity in tumor cell recognition and suitable chemical properties. Here, we summarize the state of the art concerning the HER2＋ breast cancer and anti-HER2 therapy, in particular deep-ening the contribution of the nanomedicine. Description of preclinical studies performed with HER2-targeted nanoparticles for HER2＋ breast cancer therapy will be preceded by an overview on HER2-targeting molecules and nano-conjugation strategies. Further investigation will be necessary to introduce these nano-drugs in clinical prac-tice; however promising results encourage an upcoming translation of this research for the next future.

Private somatic mutations identified with liquid biopsy lead tumor progression in solid cancers

Aim:Primary tumors can be divided into oncogene-addicted(e.g.,lung)and non-oncogene addicted(e.g.,breast).Only the former group has an Achilles-heel single gene for successful target therapy,whereas the latter has mutations of multiple causative genes.Currently,tissue biopsy used for genetic surveys do not give a complete picture of the molecular profile and clonal evolution,but only provide static information over time.Methods:A series of 133 patients with 16 different solid tumors were enrolled.Blood samples were collected and cell-free DNA(cfDNA)was extracted.cfDNA libraries were analyzed using AVENIO circulating tumor DNA(ctDNA)Expanded Kit and Illumina NextSeq 550 for sequencing was used.In order to evaluate the clinical evolution over time,a second cfDNA analysis was performed after a mean interval of 2 months.Results:Through the cfDNA liquid biopsy,we found 89 pathogenic variants in 54 genes.Breast,lung,and prostate cancers showed the largest number of mutated genes.TP53,PIK3CA,FGFR3,KRAS,and ERBB2 were the most frequently mutated genes among 16 different tumors.Gene distribution didn’t show any type of prevalence.In particular,every patient with disease progression seems to have a“private”combination of gene pair mutations,with TP53 as the most frequently mutated gene.Conclusion:We showed that the clonal evolution of tumors includes a private combination of genes,regardless of tumor type.In the future,the cancer treatment can be the targeted therapy against specific tumor mutation(s).The present approach seems promising to both identify key cancer genes and follow clonal evolution over time.