Oligometastatic Prostate Cancer: History
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Subjects: Oncology
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chiara tordonato

The oligometastatic prostate cancer state is defined as the presence of a number of lesions ≤ 5 and has been significantly correlated with better survival if compared to a number of metastases > 5. In particular, patients in an oligometastatic setting could benefit from a metastates directed therapy, which could control the disease delaying the start of systemic therapies. For this reason, the selection of true-oligometastatic patients who could benefit from such approach is particularly important in this setting.

  • oligometastatic prostate cancer
  • biomarker
  • miRNA
  • CTC
  • epi-miRNA

1. Introduction

Prostate cancer (PCa) is the most commonly diagnosed solid-organ malignancy and the second leading cause of cancer death in men worldwide [1]. Despite the high long-term survival in localized PCa, metastatic PCa remains largely associated with an overall low survival rate [2].
Recently, a growing interest is directed towards oligometastatic prostate cancer (OMPC), as the presence of a number of lesions ≤ 5 has been significantly correlated with better survival if compared to a number of metastases > 5 [3]. The oligometastatic concept was introduced for the first time by Hellman and Weichselbaum in 1995 to describe an intermediate phase between localized disease and extensive metastatic state [4]. To date, there is still no univocal definition of the oligometastatic state, even if in the scientific community, it is commonly considered as the presence of up to 3–5 lesions [5][6]. It is necessary to distinguish between two conditions of OMPC: synchronous OMPC (metastases that are already detectable at the initial diagnosis of primary tumor) and metachronous OMPC (metastases that are detected or become clinically evident at later stages of the disease course after initiation of treatment of the primary tumor treatment). Our review examines the latter scenario.
The efficacy of local ablative treatments directed towards metastatic lesions (metastases directed treatments—MDTs) in patients with OMPC was extensively investigated, with the aim of preventing the systemic spread of the disease and delaying the start of systemic androgen deprivation therapies (ADT) [1][7][8][9][10][11][12][13][14]. Nevertheless, the use of MDTs is still controversial due to the paucity of prospective randomized efforts. Notably, the publication of results from the SABR-COMET, STOMP and ORIOLE trials has fostered further research in the field, and upcoming evidence is likely to further modify the treatment scenario for this subset of patients [15][16][17]. In this perspective, ongoing studies such as the RADIOSA trial, a randomized phase II clinical trial [18] aiming to compare stereotactic body radiotherapy (SBRT) alone and in combination with 6 months ADT for the treatment of oligorecurrent-castration-sensitive-PCa (OCS-PCa), could foster the use of MDT in a selected subset of PCa patients.
With the emerging use of whole-body magnetic resonance imaging (WB-MRI) and Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), it has become easier to detect the presence of metastases in patients with early biochemical recurrence [19][20][21][22][23][24]. Despite the accuracy of these investigations, it is likely that a number of patients who are already polimetastatic will escape detection, especially at low prostate-specific antigen (PSA) levels, with negative consequences on correct clinical choices [25][26].
Since the oligometastatic state has a peculiar behavior as compared with heavy burden disease, the existence of distinct underlying biological and molecular mechanisms was hypothesized [27]. The use of PSA alone, due to its poor specificity, seems to be increasingly limited in discerning the different categories of PCa patients; therefore, the identification of other markers could provide additional information to individuate the correct prognosis and consequently propose the best treatment course, especially in OMPC [28]. Ideally, these analytes should be easily obtainable in a non-invasive manner, easy to implement across facilities, reproducible and as inexpensive as those that can be collected from serum.
For these reasons, the identification of novel biomarkers could potentially improve the treatment of advanced PCa by identifying selected oligometastatic patients who could benefit from MDT. 

2. Emerging Biomarkers for the Identification of True Oligometastatic Patients Eligible for MDT

2.1. Liquid Biopsy and Next Generations Sequencing (NGS)

Definitive diagnosis of PCa is traditionally based on histopathological analysis. Nevertheless, due to the multifocal nature of most PCas [29], as the tumor progresses, the static result from a biopsy sample will become even more inadequate to reflect dynamics of tumor evolution and its underlying biological modifications under the selective pressure of cancer therapies. These difficulties can be ascribed to the intrinsic difficulties in obtaining biopsy samples from metastases and to the inability to perform selective genetic tests on biopsy-derived tissue. Furthermore, complications may also arise from the invasive nature of biopsy procedures, which make not all cancer patients eligible for surgery due to their intrinsic fragility.
Nowadays, even with new imaging technologies allowing an increasingly early detection, the diagnosis of oligometastasis is currently based exclusively on traditional radiological investigations. Nevertheless, objective categorization of true oligometastatic patients from the ones with a trend to progress to poly-metastatic patients relies on the profile of the biological behavior of the tumor; for this purpose, a minimally invasive real-time monitoring method could be beneficial for both patients and clinicians. This could avoid expensive treatments with limited clinical benefit and potential associated toxicity or, alternatively, provide a group of oligometastatic patients with curative treatment.
Liquid biopsy has recently emerged as a promising minimally invasive approach allowing to overcome the static bioptic approach and to reflect the dynamic tumor modifications over time, specifically those involving its genomic evolution [29][30]. Through liquid biopsy, different biomarkers, commonly extracted from blood, urine or saliva, can be characterized, including circulating tumor cells (CTCs), circulating cell-free DNA (cfDNA) such as circulating tumor DNA (ctDNA), miRNA and exosomes [31][32].

2.2. Circulating Tumor Cells (CTCs)

CTCs are cancer cells originating from macroscopic tumor sites (either primary or metastases) and released into the bloodstream. Here, CTCs could be found as single CTCs or CTC clusters, with the latter being more often associated with a higher metastatic potential [33][34].
Since CTCs may reflect the current tumor status, there is a growing interest in identifying genomic alterations in CTCs that could aid the decision workflow in targeted therapies.
A recent study by Gkontela et al. [34] provided insights about how CTC clusters intrinsic differences have a direct impact on the DNA methylation status and thus influence important regulatory regions related to cancer proliferation, suggesting that agents disrupting these clusters could suppress spontaneous metastatic formations.
A 2020 study by Faugeroux et al. [35] emphasized the potential of CTCs in representing metastases mutational content and tumor diversity that would be otherwise inaccessible. Therefore, by offering real-time monitoring of a constantly evolving disease and detecting potentially critical SNPs via liquid biopsy, CTC sequencing can serve an unmet need for optimal therapy selection and precision medicine.

2.3. Circulating Cell-Free DNA (cfDNA)

cfDNA, or ctDNA, shed from apoptotic and necrotic cells, comprises both genomic and mitochondrial DNA and can be used as a biomarker to characterize the mutational and epigenomic status in advanced solid tumors [36]. The ctDNA concentration in plasma was correlated with both tumor size and clinical stage of the malignancy [37][38]. Additionally, the half-life of these molecules is relatively short (1–2 h), which provides real-time insight into the tumor status. Clinical studies showed that healthy individuals present lower cfDNA levels, indicating a relatively simple analysis involving the mere cfDNA quantification as a valuable biomarker [39][40]. The exact measure of cfDNA can be challenging due to the high fragmentation degree and the overall low concentration. The main source of cfDNA is also controversial. In fact, while the serum presents a higher concentration of cfDNA molecules, serum-derived samples are often contaminated by a clotting process, and therefore plasma is actually considered a more valuable cfDNA source despite the lower overall concentration [41][42].
As the total cfDNA increases with the tumor growth, it was hypothesized that cfDNA derives directly from living tumor cells and that CTCs could be an alternative cfDNA source [43].

2.4. Exosomes

It was speculated that a better understanding of the determinants of oligometastases could come from molecular studies on the signaling between the primary tumor and its metastatic sites. Exosomes are nanoscale extracellular vesicles that have a role in the exchange of genetic material, implicated in tumor cell growth and invasion, favoring disease dissemination by creating a pro-tumor micro-environment and the creation of premetastatic niches [44][45][46][47].
By analyzing the exosome proteins derived from PCa cells, the researchers found a high level of molecules stimulating tumor cell migration and metastases, such as the b4 and avb6 integrins, vinculin and the Trop-2 transmembrane glycoprotein [48][49]. In addition, cancer-derived exosomes can promote EMT through miRNAs, which play an important role in the conversion from benign to malignant cancers and in the regulation of the response to docetaxel, such as miR-34 in prostate cancer cells and cell-derived exosomes targeting Bcl-2 [50].
On the basis of these findings, the role of exosomes in the early phases of tumor metastatization seems to make them interesting and worth to be explored biomarkers for future diagnostic approaches in the oligometastatic setting.

3. Conclusions

Further research is needed to evaluate novel biomarkers as promising tools to be implemented in the therapeutic workflow in the oligometastatic setting. Overall scientific evidence analyzed here will be applied to the prospective phase II RADIOSA trial [18]. In particular, a deeper understanding of the molecular workings underlying the oligometastatic clinical entity could unravel novel suitable biomarkers that could aid the clinical management of the oligometastatic PCa patient. The most attractive ones are CTCs, cf DNA and miRNA, with technologies such as liquid biopsies and NGS expected to play an important role in the clinical setting.
Additional molecular biology research is also needed in order to establish and define consistent isolation and quantification methods for specific biomarkers assessment. In this scenario, different ongoing trials for biomarker identification in PCa [51] (Table 1) or ongoing trials as the phase 2 Oriole trial and the RADIOSA trial [17][18] might provide additional insights on the biology of the oligometastatic state, laying the bases for the identification of new biomarkers for the accurate outlining of true oligometastatic patients. Overall, this could pave the way to a better personalized medicine approach in the OMPC setting.
Table 1. Summary of ongoing trials (all in the recruiting phase) for the identification of predictive biomarkers for prostate cancer.
Trial ID Trial Description Study Type Conditions Interventions Outcomes Measures Estimated Primary Completion Date
NCT04324983 BioPoP, Identification of Predictive Biomarkers Interventional Prostate Cancer
Recurrent		 Blood sample -Rate of complete biochemical response
-Prostate cancer-specific treatment-free survival after salvage surgery
-Questionnaire Quality of life		 December 2021
NCT03902951 Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer Interventional, Phase II -Metastatic Prostate
Adenocarcinoma
-Recurrent Prostate
Carcinoma		 -Drugs: Abiraterone Acetate/Apalutamide/Leuprolide
Acetate
-Stereotactic Body Radiation Therapy		 -Percent of patients achieving a PSA < 0.05 ng/mL
-Time to biochemical/ radiographic progression
-Time to initiation of alternative antineoplastic therapy
-Prostate cancer-specific Survival
-Health-related quality of life
-Biomarker analysis		 July 2021
NCT03421015 Genetic Analysis of Prostate Cancer to Identify PredictiveMarkers of Disease Relapse or Metastatic Evolution Observational Retrospective Prostate Cancer - -The genetic alteration frequencies of TMPRSS2-
ERG gene fusion
•Frequency of amplification
of proto-oncogenes (MYC,
AR, PIK3CA)
•Frequency of mutations
or deletions of tumor suppressor genes (PTEN, TP53, NKX3-1),
•Frequency of point mutations modifying protein function		 July 2020

This entry is adapted from the peer-reviewed paper 10.3390/cancers13133278

References

  1. Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA Cancer J. Clin. 2016, 66, 7–30.
  2. Litwin, M.S.; Tan, H.J. The diagnosis and treatment of prostate cancer: A review. JAMA J. Am. Med. Assoc. 2017, 317, 2532–2542.
  3. Singh, D.; Yi, W.S.; Brasacchio, R.A.; Muhs, A.G.; Smudzin, T.; Williams, J.P.; Messing, E.; Okunieff, P. Is there a favorable subset of patients with prostate cancer who develop oligometastases? Int. J. Radiat. Oncol. Biol. Phys. 2004, 58, 3–10.
  4. Hellman, S.; Weichselbaum, R.R. Oligometastases. J. Clin. Oncol. 1995, 13, 8–10.
  5. De Bleser, E.; Tran, P.T.; Ost, P. Radiotherapy as metastasis-directed therapy for oligometastatic prostate cancer. Curr. Opin. Urol. 2017, 27, 587–595.
  6. Lievens, Y.; Guckenberger, M.; Gomez, D.; Hoyer, M.; Iyengar, P.; Kindts, I.; Méndez Romero, A.; Nevens, D.; Palma, D.; Park, C.; et al. Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document. Radiother. Oncol. 2020, 148, 157–166.
  7. Mathieu, R.; Korn, S.M.; Bensalah, K.; Kramer, G.; Shariat, S.F. Cytoreductive radical prostatectomy in metastatic prostate cancer: Does it really make sense? World J. Urol. 2017, 35, 567–577.
  8. Fossati, N.; Trinh, Q.D.; Sammon, J.; Sood, A.; Larcher, A.; Sun, M.; Karakiewicz, P.; Guazzoni, G.; Montorsi, F.; Briganti, A.; et al. Identifying optimal candidates for local treatment of the primary tumor among patients diagnosed with metastatic prostate cancer: A SEER-based Study. Eur. Urol. 2015, 67, 3–6.
  9. Löppenberg, B.; Dalela, D.; Karabon, P.; Sood, A.; Sammon, J.D.; Meyer, C.P.; Sun, M.; Noldus, J.; Peabody, J.O.; Trinh, Q.D.; et al. The Impact of Local Treatment on Overall Survival in Patients with Metastatic Prostate Cancer on Diagnosis: A National Cancer Data Base Analysis. Eur. Urol. 2017, 72, 14–19.
  10. McMillan, D.C. Systemic inflammation, nutritional status and survival in patients with cancer. Curr. Opin. Clin. Nutr. Metab. Care 2009, 12, 223–226.
  11. Camp, R.L.; Dolled-Filhart, M.; Rimm, D.L. X-tile: A new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin. Cancer Res. 2004, 10, 7252–7259.
  12. Fanetti, G.; Marvaso, G.; Ciardo, D.; Rese, A.; Ricotti, R.; Rondi, E.; Comi, S.; Cattani, F.; Zerini, D.; Fodor, C.; et al. Stereotactic body radiotherapy for castration-sensitive prostate cancer bone oligometastases. Med. Oncol. 2018, 35.
  13. Jereczek-Fossa, B.A.; Fanetti, G.; Fodor, C.; Ciardo, D.; Santoro, L.; Francia, C.M.; Muto, M.; Surgo, A.; Zerini, D.; Marvaso, G.; et al. Salvage Stereotactic Body Radiotherapy for Isolated Lymph Node Recurrent Prostate Cancer: Single Institution Series of 94 Consecutive Patients and 124 Lymph Nodes. Clin. Genitourin. Cancer 2017, 15, e623–e632.
  14. Augugliaro, M.; Pepa, M.; Marvaso, G.; Jereczek-Fossa, B.A. Re: Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. Eur. Urol. 2021, 79, 889–890.
  15. Palma, D.A.; Olson, R.; Harrow, S.; Gaede, S.; Louie, A.V.; Haasbeek, C.; Mulroy, L.; Lock, M.; Rodrigues, G.B.; Yaremko, B.P.; et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): A randomised, phase 2, open-label trial. Lancet 2019, 393, 2051–2058.
  16. Ost, P.; Reynders, D.; Decaestecker, K.; Fonteyne, V.; Lumen, N.; DeBruycker, A.; Lambert, B.; Delrue, L.; Bultijnck, R.; Claeys, T.; et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: A prospective, randomized, multicenter phase II trial. J. Clin. Oncol. 2018, 36, 446–453.
  17. Phillips, R.; Shi, W.Y.; Deek, M.; Radwan, N.; Lim, S.J.; Antonarakis, E.S.; Rowe, S.P.; Ross, A.E.; Gorin, M.A.; Deville, C.; et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020, 6, 650–659.
  18. Marvaso, G.; Ciardo, D.; Corrao, G.; Gandini, S.; Fodor, C.; Zerini, D.; Rojas, D.P.; Augugliaro, M.; Bonizzi, G.; Pece, S.; et al. Radioablation +/− hormonotherapy for prostate cancer oligorecurrences (Radiosa trial): Potential of imaging and biology (AIRC IG-22159). BMC Cancer 2019, 19, 1–7.
  19. Ryan, A.M.; Power, D.G.; Daly, L.; Cushen, S.J.; Ní Bhuachalla, E.; Prado, C.M. Cancer-associated malnutrition, cachexia and sarcopenia: The skeleton in the hospital closet 40 years later. Proc. Nutr. Soc. 2016, 75, 199–211.
  20. McMillan, D.C.; Elahi, M.M.; Sattar, N.; Angerson, W.J.; Johnstone, J.; McArdle, C.S. Measurement of the Systemic Inflammatory Response Predicts Cancer-Specific and Non-Cancer Survival in Patients with Cancer. Nutr. Cancer 2001, 41, 64–69.
  21. Wei, J.; Zhu, H.; Liao, X. Trigger pSA predicting recurrence from positive choline PET/CT with prostate cancer after initial treatment. Oncotarget 2018, 9, 14630–14641.
  22. Perera, M.; Papa, N.; Christidis, D.; Wetherell, D.; Hofman, M.S.; Murphy, D.G.; Bolton, D.; Lawrentschuk, N. Sensitivity, Specificity, and Predictors of Positive 68Ga–Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis. Eur. Urol. 2016, 70, 926–937.
  23. Padhani, A.R.; Lecouvet, F.E.; Tunariu, N.; Koh, D.-M.; De Keyzer, F.; Collins, D.; Sala, E.; Schlemmer, H.P.; Petralia, G.; Vargas, H.A.; et al. METastasis Reporting and Data System for Prostate Cancer: Practical Guidelines for Acquisition, Interpretation, and Reporting of Whole-body Magnetic Resonance Imaging-based Evaluations of Multiorgan Involvement in Advanced Prostate Cancer. Eur. Urol. 2017, 71, 81–92.
  24. Tunariu, N.; Blackledge, M.; Messiou, C.; Petralia, G.; Padhani, A.; Curcean, S.; Curcean, A.; Koh, D.-M. What’s New for Clinical Whole-body MRI (WB-MRI) in the 21st Century. Br. J. Radiol. 2020, 93.
  25. Ray-Coquard, I.; Cropet, C.; Van Glabbeke, M.; Sebban, C.; Le Cesne, A.; Judson, I.; Tredan, O.; Verweij, J.; Biron, P.; Labidi, I.; et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009, 69, 5383–5391.
  26. Van Leeuwen, P.J.; Stricker, P.; Hruby, G.; Kneebone, A.; Ting, F.; Thompson, B.; Nguyen, Q.; Ho, B.; Emmett, L. 68Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU Int. 2016, 117, 732–739.
  27. Yang, W.; Bai, Y.; Xiong, Y.; Zhang, J.; Chen, S.; Zheng, X.; Meng, X.; Li, L.; Wang, J.; Xu, C.; et al. Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism. Nature 2016, 531, 651–655.
  28. Zhang, W.; Wu, Y.; Zhang, Z.; Guo, Y.; Wang, R.; Wang, L.; Mao, S.; Zhang, J.; Yao, X. Controlling Nutritional Status score: A new prognostic indicator for patients with oligometastatic prostate cancer. Curr. Probl. Cancer 2019, 43, 461–470.
  29. Ghosh, R.K.; Pandey, T.; Dey, P. Liquid biopsy: A new avenue in pathology. Cytopathology 2019, 30, 138–143.
  30. Arancio, W.; Belmonte, B.; Castiglia, M.; Di Napoli, A.; Tripodo, C. Tissue Versus Liquid Biopsy: Opposite or Complementary? In Liquid Biopsy in Cancer Patients; Humana Press: Cham, Switzerland, 2017; pp. 41–49.
  31. Wang, J.; Ni, J.; Beretov, J.; Thompson, J.; Graham, P.; Li, Y. Exosomal microRNAs as liquid biopsy biomarkers in prostate cancer. Crit. Rev. Oncol. Hematol. 2020, 145, 4–10.
  32. Stelcer, E.; Konkol, M.; Głȩboka, A.; Suchorska, W.M. Liquid biopsy in oligometastatic prostate cancer—A biologist’s point of view. Front. Oncol. 2019, 9, 1–19.
  33. Hegemann, M.; Stenzl, A.; Bedke, J.; Chi, K.N.; Black, P.C.; Todenhöfer, T. Liquid biopsy: Ready to guide therapy in advanced prostate cancer? BJU Int. 2016, 118, 855–863.
  34. Gkountela, S.; Castro-Giner, F.; Szczerba, B.M.; Vetter, M.; Landin, J.; Scherrer, R.; Krol, I.; Scheidmann, M.C.; Beisel, C.; Stirnimann, C.U.; et al. Circulating Tumor Cell Clustering Shapes DNA Methylation to Enable Metastasis Seeding. Cell 2019, 176, 98–112.e14.
  35. Faugeroux, V.; Lefebvre, C.; Pailler, E.; Pierron, V.; Marcaillou, C.; Tourlet, S.; Billiot, F.; Dogan, S.; Oulhen, M.; Vielh, P.; et al. An Accessible and Unique Insight into Metastasis Mutational Content Through Whole-exome Sequencing of Circulating Tumor Cells in Metastatic Prostate Cancer. Eur. Urol. Oncol. 2020, 3, 498–508.
  36. Lowes, L.E.; Bratman, S.V.; Dittamore, R.; Done, S.; Kelley, S.O.; Mai, S.; Morin, R.D.; Wyatt, A.W.; Allan, A.L. Circulating tumor cells (CTC) and cell-free DNA (cfDNA)workshop 2016: Scientific opportunities and logistics for cancer clinical trial incorporation. Int. J. Mol. Sci. 2016, 17, 1505.
  37. Thierry, A.R.; Mouliere, F.; Gongora, C.; Ollier, J.; Robert, B.; Ychou, M.; del Rio, M.; Molina, F. Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts. Nucleic Acids Res. 2010, 38, 6159–6175.
  38. Bettegowda, C.; Sausen, M.; Leary, R.J.; Kinde, I.; Wang, Y.; Agrawal, N.; Bartlett, B.R.; Wang, H.; Luber, B.; Alani, R.M.; et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl. Med. 2014, 6.
  39. Elshimali, Y.; Khaddour, H.; Sarkissyan, M.; Wu, Y.; Vadgama, J. The Clinical Utilization of Circulating Cell Free DNA (CCFDNA) in Blood of Cancer Patients. Int. J. Mol. Sci. 2013, 14, 18925–18958.
  40. Salvi, S.; Gurioli, G.; De Giorgi, U.; Conteduca, V.; Tedaldi, G.; Calistri, D.; Casadio, V. Cell-free DNA as a diagnostic marker for cancer: Current insights. Oncotargets Ther. 2016, 9, 6549–6559.
  41. Belic, J.; Koch, M.; Ulz, P.; Auer, M.; Gerhalter, T.; Mohan, S.; Fischereder, K.; Petru, E.; Bauernhofer, T.; Geigl, J.B.; et al. Rapid Identification of Plasma DNA Samples with Increased ctDNA Levels by a Modified FAST-SeqS Approach. Clin. Chem. 2015, 61, 838–849.
  42. Heitzer, E.; Ulz, P.; Geigl, J.B. Circulating Tumor DNA as a Liquid Biopsy for Cancer. Clin. Chem. 2015, 61, 112–123.
  43. Cheng, F.; Su, L.; Qian, C. Circulating tumor DNA: A promising biomarker in the liquid biopsy of cancer. Oncotarget 2016, 7, 48832–48841.
  44. Luga, V.; Zhang, L.; Viloria-Petit, A.M.; Ogunjimi, A.A.; Inanlou, M.R.; Chiu, E.; Buchanan, M.; Hosein, A.N.; Basik, M.; Wrana, J.L. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 2012, 151, 1542–1556.
  45. Peinado, H.; Alečković, M.; Lavotshkin, S.; Matei, I.; Costa-Silva, B.; Moreno-Bueno, G.; Hergueta-Redondo, M.; Williams, C.; García-Santos, G.; Ghajar, C.M.; et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 2012, 18, 883–891.
  46. Chowdhury, R.; Webber, J.P.; Gurney, M.; Mason, M.D.; Tabi, Z.; Clayton, A. Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts. Oncotarget 2015, 6, 715–731.
  47. Conti, A.; D’Elia, C.; Cheng, M.; Santoni, M.; Piva, F.; Brunelli, M.; Lopez-Beltran, A.; Giulietti, M.; Scarpelli, M.; Pycha, A.; et al. Oligometastases in Genitourinary Tumors: Recent Insights and Future Molecular Diagnostic Approach. Eur. Urol. Suppl. 2017, 16, 309–315.
  48. Kawakami, K.; Fujita, Y.; Kato, T.; Mizutani, K.; Kameyama, K.; Tsumoto, H.; Miura, Y.; Deguchi, T.; Ito, M. Integrin β4 and vinculin contained in exosomes are potential markers for progression of prostate cancer associated with taxane-resistance. Int. J. Oncol. 2015, 47, 384–390.
  49. Trerotola, M.; Ganguly, K.K.; Fazli, L.; Fedele, C.; Lu, H.; Dutta, A.; Liu, Q.; De Angelis, T.; Riddell, L.W.; Riobo, N.A.; et al. Trop-2 is up-regulated in invasive prostate cancer and displaces FAK from focal contacts. Oncotarget 2015, 6, 14318–14328.
  50. Pan, J.; Ding, M.; Xu, K.; Yang, C.; Mao, L.J. Exosomes in diagnosis and therapy of prostate cancer. Oncotarget 2017, 8, 97693–97700.
  51. Home—ClinicalTrials.gov. Available online: (accessed on 28 April 2021).
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