Page 54 - ITPS-8-3

INNOSC Theranostics and
Pharmacological Sciences Precision medicine and beyond in oncology

4.5.2. Epigenetic and microRNA-mediated improved. 126,127 Nanoparticles can also help deliver
reprogramming of the TME substances to tumor cells or immune cells to induce tumor
MicroRNAs (miRNAs) also influence the immunological cell death or boost antitumor immunity, such as fat mass and
and angiogenic features of the TME. In HCC, certain obesity-associated protein inhibitors and tumor-associated
128
miRNAs, such as miR-139-5p, directly target WTAP antigens, into HCC. Despite their strong potential,
to suppress epithelial-mesenchymal transition, thereby nanoparticles are still under consideration due to concerns
129
reducing metastasis and altering the TME toward a less regarding long-term safety and biodegradability.
invasive phenotype. 116,117 In addition, miR-126, another Interestingly, treatment targeting TME can significantly
critical regulator, is stabilized and processed to interact reduce the relapse rate. For pediatric patients with high-
with METTL14 in a N -methyladenosine-dependent risk acute lymphoblastic leukemia, blinatumomab
6
manner, ultimately, to exert anti-angiogenic effects (bispecific antibodies) showed a significantly higher
and inhibit the metastatic potential of HCC. As they event-free survival than consolidation chemotherapy (31%
118
modulate tumorigenesis, metastasis, or suppression, versus 57%, p<0.001), with an HR of 0.33 (95% confidence
130
they can be valuable biomarkers predicting prognosis or interval: 0.18–0.61). Given the significant role of TME
treatments. Regarding treatments, inhibitors targeting in relapse and metastasis, therapies targeting the TME are
genes modulating N -methyladenosine regulators such expected to yield superior clinical outcomes.
6
as METTL3, FTO, and ALKBH5 have been developed.
119
Notably, STM2457, a potent methyltransferase-like 3 5. Precision medicine and AI
6
inhibitor, has been shown to reduce N -methyladenosine Precision medicine is heavily reliant on big data sets,
modification levels, disrupt leukemogenic gene yet biomedical knowledge is often fragmented across
expression programs, and recondition the immune manuscripts and non-standardized data repositories,
TME in multiple malignancies, including acute myeloid making the effort of parsing through the existing
leukemia, intrahepatic cholangiocarcinoma, prostate literature a time-consuming and intensive task. While
131
cancer, and Sonic Hedgehog medulloblastoma. 120-123 the implementation of AI in biomedical research and
In HCC, STM2457 enhances the efficacy of lenvatinib clinical practice is not without its challenges, AI shows
by modulating both tumor-intrinsic signaling and the promise as a powerful investigative and diagnostic tool in
microenvironment, representing a bridge between cancer research. AI-based summary tools can be used by
124
miRNA regulations, epigenetic remodeling, and TME clinicians to stay updated on the most recent developments
reprogramming. However, research in this area remains in cancer diagnosis and treatment. Specifically, this section
in its early stages and is currently limited to pre-clinical will focus on three key areas where AI is being applied:
settings. Other newer therapeutic approaches include gene cancer diagnosis, drug development, and clinical practice,
therapy, proteolysis-targeting chimera, and the targeting of and its various applications, as summarized in Figure 3.
119
upstream regulators in cancer. So far, several proteolysis-
targeting chimeras have entered Phase I and Phase II 5.1. AI applications in histopathology and radiology
trials, marking a promising new chapter in targeted cancer for cancer diagnosis
treatment. Histopathologic grading and radiologic imaging are often
key elements of obtaining a cancer diagnosis. AI has shown
4.5.3. Targeted delivery and localized modulation of promise in augmenting the detection and assessment of
the TME
cancerous lesions found in these images. Conventionally,
Additional strategies to overcome physical and metabolic histological preparation and assessment of tumor samples
barriers in the TME include localized chemotherapy and can be labor-intensive and prone to observer variability.
132
nanotechnology. Hepatic arterial infusion chemotherapy, Certain tumors, such as those derived from breast or
which allows high-dose drug delivery to the liver, prostate tissue, have diverse presentations and thus are
reduces systemic toxicity and has shown efficacy in more susceptible to observer variability than others. 133,134
advanced infiltrative HCC when used alongside targeted While errors in pathological diagnosis are relatively low
agents. Nanoparticles offer another promising platform and do not pose clinically significant concerns at the
125
to directly deliver small interfering RNA, clustered population level, the movement toward precision medicine
regularly interspaced short palindromic repeats- may make these faults increasingly decisive in the care of
associated protein-9 nuclease-synthetic guide RNA, or individual patients. 135,136 Recent advances in imaging and
immunostimulatory agents to tumor or immune cells. By storage technology have allowed the routine digitization
silencing the oncogenes through the delivery system, the of conventional glass slides in pathology laboratories.
efficacy of anti-PD-1 therapy against CRC has markedly Machine learning algorithms have been developed to

Volume 8 Issue 3 (2025) 48 doi: 10.36922/ITPS025140018