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Tumor Discovery Melanoma exosomes in metastasis

their cargo – could offer a novel therapeutic strategy to affecting interactions with the TME. 76,77 Similarly, targeting
combat melanoma metastasis. 70 oncogenic exosomal RNAs, such as miRNAs and long non-
coding RNAs, offers a novel approach to suppress tumor
5. Diagnostic and therapeutic implications growth and immune escape. 78,79

The unique composition of melanoma-derived exosomes The table below summarizes exosome-associated
presents opportunities for their use as biomarkers and therapeutic targets in melanoma 80,81 (Table 1).
therapeutic targets.
By targeting exosome-associated molecules and
5.1. Exosomes as biomarkers pathways, novel therapeutic strategies could limit
melanoma progression, enhance immune responses, and
Exosomes, which can be extracted from biological improve drug delivery efficiency, thereby offering new
fluids such as blood, urine, and lymphatic fluid, show directions for precision oncology.
great promise as a resource for liquid biopsies. Specific
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miRNAs and proteins found in exosomes have been linked 5.3. Limitations and challenges of exosome-based
to disease progression, treatment outcomes, and prognosis. therapies in melanoma
For example, elevated levels of certain exosomal miRNAs Exosome-based therapeutic strategies show great potential
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have been identified in advanced stages of melanoma, in the treatment of melanoma by targeting metastatic
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underscoring their potential as non-invasive biomarkers pathways and modulating the immune system. However,
for early detection and disease monitoring. 74 the clinical application of exosome-based therapies faces
5.2. Therapeutic targeting of exosomes significant challenges. One significant obstacle is the
heterogeneity of exosomal cargo, which complicates the
Targeting exosomes represents a promising therapeutic predictability and effectiveness of treatments. Exosomes
strategy in melanoma, as they contribute to tumor are naturally heterogeneous, carrying a wide variety of
progression, immune modulation, and therapy resistance. proteins, lipids, and RNAs, depending on their cell of
Approaches to inhibit exosome release, modify their cargo, origin and the conditions under which they are produced.
or block their uptake could disrupt tumor-promoting This variability makes it difficult to standardize exosome
communication pathways. In addition, engineered preparations, which can result in inconsistent therapeutic
exosomes offer potential for targeted drug delivery, outcomes. Differences in cargo composition can lead
improving therapeutic efficacy while minimizing off-target to unpredictable interactions with target cells, further
effects. 22 complicating clinical applications.

However, off-target effects remain a major concern, Off-target effects remain a major concern for
as these therapies may affect non-target tissues, leading exosome-based therapies. These therapies may affect
to unwanted side effects and reduced efficacy. Exosomes non-target tissues, leading to undesirable side effects
can interact with unintended cell types, potentially causing and reduced therapeutic efficacy. Exosomes can interact
non-specific distribution and unintended interactions. with unintended cell types, potentially leading to non-
The biodistribution of exogenously administered specific distribution and unintended interactions. The
exosomes is often unpredictable, resulting in unintended biodistribution of exogenously administered exosomes is
accumulation in non-target organs or tissues. This non- often unpredictable, resulting in unintended accumulation
specific distribution can lead to unwanted side effects, in non-target organs or tissues. This non-specific
such as inflammation or toxicity in healthy tissues, distribution can lead to side effects such as inflammation
thereby compromising overall therapeutic efficacy. or toxicity in healthy tissues, thereby compromising the
These limitations are further discussed in Section 4.3, overall therapeutic efficacy. In addition, exosomes may
which provides a more comprehensive perspective on bind to non-target receptors or cells, further increasing
the challenges associated with the clinical application of the risk of adverse reactions. These off-target interactions
exosome-based therapies. not only reduce treatment effectiveness but also pose
Recent studies have identified several key exosomal significant safety concerns, limiting the widespread use of
proteins, signaling pathways, and RNA molecules as exosome-based therapies.
potential therapeutic targets in melanoma. Regulators of A significant challenge in the clinical translation of
exosome biogenesis, cargo sorting, and uptake play crucial exosome-based therapies is the scalability of exosome
roles in metastasis and immune evasion. For example, production. Producing exosomes in large quantities with
Rab GTPases, tetraspanins, and ESCRT-associated consistent quality and potency remains a major hurdle.
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proteins influence exosome secretion and composition, The isolation and purification methods for exosomes need

Volume 4 Issue 2 (2025) 8 doi: 10.36922/td.7108