Background
Circulating tumor cells
CTCs and spatial heterogeneity
Tumor type | Findings | References |
---|---|---|
Breast Cancer | Possible escape mechanism to endocrine therapy due to high percentage of ER negative CTC | [20] |
Discordance in HER2 status between primary and metastatic status influencing response to anticancer treatment | [21] | |
Prostate Cancer | AR signaling modification upon hormonal treatments influences outcomes | [22] |
Wnt activation leading to hormonal treatment failure | [23] | |
CTC heterogeneity as indicator for first line treatment | [24] | |
AR-V7 nuclear expression predicts better response to chemotherapy compared to AR signaling inhibitors | [25] | |
Colorectal Cancer | 50% concordance in KRAS status between primary tumor and CTC as surrogate of spatial heterogeneity | [26] |
Differential phenotype of CTC from right and left side may explain different metastasization patterns | [27] | |
Hepatocellular Cancer | EMT of CTC relates with metastasization process | [28] |
CTCs and temporal heterogeneity
Tumor type | Findings | References |
---|---|---|
Colorectal Cancer | CTC KRAS status changes upon treatment and may potentially anticipate sensitivity to chemotherapy regimens | [33] |
EGFR-mutated Non Small Cell Lung Cancer | Detection of acquired resistance mechanisms after first line EGFR-TKI treatment | |
HER2-negative Breast Cancer | Assessment of PIK3CA during systemic treatment could inform about primary or acquired resistance | [38] |
Circulating leukocytes
Tumor type | Findings | References |
---|---|---|
Pancreatic Ductal Adenocarcinoma | TCR features are correlated with survival in immunotherapy treated patients | [41] |
Melanoma | TCR repertoire profiling is associated with immunotherapy response | |
Baseline frequency of CD14 + CD16-HLA-DRhi monocytes, CD69 + MIP-1β + NK cells, and PD-1 + CD56+ T cells are potential predictors of clinical response in patients treated with immunotherapy | ||
The increase of central memory CD4+ T cells and the decrease of dysfunctional PD-1 + CD38hi CD8+ cells during immunotherapy are correlated with response. | ||
Levels of circulating CD33 + CD11b + HLA-DR- myeloid derived suppressor and distinct CD4+ and CD8+ memory T cell subsets are correlated with survival of immunotherapy treated patients. | ||
Lung Cancer | TCR repertoires of PD-1+ CD-8+ lymphocytes are correlated with clinical outcomes of immunotherapy treated patients | |
Baseline percentage of HLA-DR monocytes and dendritic cells are correlated to immunotherapy response | [53] | |
Melanoma and Lung Cancer | Elevated frequencies of CD4 + Foxp3- T cells, at baseline and/or during immunotherapy, are associated with a higher risk of death | [54] |
TCR profiling of lymphocytes from cancer patients
Immunoprofiling of peripheral leukocytes from cancer patients
Circulating DNA
Tumor type | Findings | References |
---|---|---|
Breast Cancer | Identification of ER mutations in ctDNA not present in DNA from tumor biopsy | [69] |
ER mutations in ctDNA is associated with resistance to endocrine therapy | ||
Identification of PIK3CA alterations in plasma-derived ctDNA | [72] | |
PIK3CA ctDNA levels are associated with response to palbociclib and fulvestrant therapy | [73] | |
HER2 mutation frequency predicts response to neratinib | [74] | |
Association of ctDNA fraction and somatic copy number alterations with worse outcomes | ||
Non Small Cell Lung Cancer | Association of EGFR mutations with survival | |
Detection of EGFR mutations in ctDNA allows to identify patients eligible for anti-EGFR treatments (FDA-approved) | [78] | |
Identification of EGFR mutations responsible of response to gefitinib | [79] | |
Identification of EGFR mutation responsible of anti-EGFR therapy resistance (e.g. T790M) | [80] | |
Longitudinal quantitative changes in ctDNA correlate with therapeutic response | [82] | |
Colorectal Cancer | ctDNA analysis allows to identify KRAS, BRAF, APC, PIK3CA, EGFR and NRAS mutations helping clinicians’ treatment strategy choice | |
Detection of EGFR and APC mutations in ctDNA to track clonal evolution and therapy response | ||
KRAS mutations in ctDNA can be detected before radiological relapse | [87] | |
Castration Sensitive Prostate Cancer | ctDNA provides complementary information to a prostate needle biopsy and could be used to guide management strategies | [89] |
Detection of AR gene alteration to monitor treatment response or resistance |
The potential role of ctDNA in metastatic disease
Circulating RNA
microRNA
Tumor type | Findings | References |
---|---|---|
Breast Cancer | Upregulation of miR-21, miR-23b, miR-200b, miR-200c levels; miR-23b and miR-190 correlated with low PFS in de novo metastatic patients; high levels of miR-200b predicted decreased OS in the HER2-negative subgroup | [101] |
Colorectal Cancer | Upregualtion of miR-103 levels were associated with lymph nodes metastases and advanced disease | [102] |
Upregulation of miR-29a | [103] | |
miR-203 and miR-141 expression discriminated metastatic from early stage patients | [104] | |
miR-21 correlated with liver metastases and TNM stage and was associated with worse OS and disease free survival | [105] | |
Decreased levels of miR-1914-3p and miR-1915-3p were found in chemoresistant patients | [106] | |
Non Small Cell Lung Cancer | High expression level of exosomal miR-222-3p, miR-23b-3p, miR-10b-3p and miR-21-5p were associated with poor OS; miR-21-5p correlated with liver metastases and TNM stage. | |
Lower expression of exosomal miR-146-5p was found in cisplatin resistant patients and was associated to short PFS | [109] | |
Pancreatic ductal adenocarcinoma | High expression of miR-155-5p was correlated with chemoresistance and poor prognosis in patients receiving gemcitabine treatment | [110] |