###### Abstract  
Exosomal heat shock proteins (Hsps) are involved in intercellular communication both in physiological and pathological conditions. They play a role in key processes of carcinogenesis including immune system regulation, cell differentiation, vascular homeostasis and metastasis formation. Thus, exosomal Hsps are emerging biomarkers of malignancies and possible therapeutic targets. Adolescents and young adults (AYAs) are patients aged 15-39 years. This age group, placed between pediatric and adult oncology, pose a particular challenge for cancer management. New biomarkers of cancer growth and progression as well as prognostic factors are desperately needed in AYAs. In this review, we attempted to summarize the current knowledge on the role of exosomal Hsps in selected solid tumors characteristic for the AYA population and/or associated with poor prognosis in this age group. These included malignant melanoma, brain tumors, and breast, colorectal, thyroid, hepatocellular, lung and gynecological tract carcinomas. The studies on exosomal Hsps in these tumors are limited; however; some have provided promising results. Although further research is needed, there is potential for future clinical applications of exosomal Hsps in AYA cancers, both as novel biomarkers of disease presence, progression or relapse, or as therapeutic targets or tools for drug delivery. exosomes; heat shock proteins; cancer; adolescents and young adults; AYA +
Footnote †: journal: Medical Oncology  
cells exposed to hypoxia, infection, increased temperature, and chemical and physical factors [1; 2; 3]. Consequently, Hsps have been found to be upregulated in cells subjected to various proteotoxic stressors as an adaptive response in order to promote cell survival. Hsps overexpression seems to be well correlated with cancer development and resistance to chemotherapy, making Hsps promising tumor biomarkers [4; 5]. Indeed, Hsps molecular chaperone levels have been found to be elevated in many cancers, and their overexpression has been associated with poor overall survival and poor response to therapy in specific cancer types [6; 7; 8; 9; 10]. The three major families of Hsps whose expressions and activities are abnormally enhanced in cancer are the Hsp60, the Hsp70, and the Hsp90 families [11]. Small Hsps and Hsp40 are also upregulated in malignancies. The small Hsps family includes molecules with a molecular weight of 12-43 kDa, e.g., Hsp20, Hsp22, and Hsp27 [12]. The most abundant eukaryotic Hsp protein is Hsp90, which is a ubiquitously expressed protein with a molecular weight of 90 kDa. Its expression level is estimated to be 1-2% of total proteins under physiological conditions [13; 14; 15]. Two cytoplasmic isoforms, Hsp90 alpha (Hsp90 AA1, Hsp90a, HspC1) and Hsp90 beta (Hsp90 AB1, Hsp90b, HspC3), and the ER homolog, glucose-regulated protein 94 (GRP94, Hsp90B1), have been distinguished [14; 15]. Hsp90 alpha and Hsp90 beta are both constitutively expressed isoforms. However, Hsp90 alpha is believed to be more inducible in response to great variety of stimuli [14; 16]. An increased level of Hsp90 alpha seems to be principally associated with tumor progression and sustained cancer cell proliferation. Hsp90 beta is primarily responsible for development of drug resistance and long-term cellular adaptations [17]. Hsp90 is expressed at 2-10 fold higher levels in cancer cells compared to normal cells and is suggested to be one of the key factors implicated in promotion of cancer cell survival and metastases [18]. Hsp70 is a chaperone that, together with Hsp90, constitutes part of the major chaperone machinery. Several Hsp70 family members have been distinguished in humans, including stress-inducible Hsp70 (Hsp72, HspA1) and constitutively expressed HSC70 (Hsp73, HspA8) [19; 20]. Each Hsp70, similar to Hsp90 proteins, is an ATP-dependent chaperone. Hsp70 and Hsp90 proteins are believed to be antiapoptotic heat shock proteins. However, the mechanisms of their action still remain controversial.