Breakthrough Clinical Results
MiraDx announced two studies to be presented at ASCO 2025, showcasing their mirSNP platform's ability to predict treatment-related toxicity and response to cancer therapies. The studies, conducted in collaboration with UCLA, analyzed germline microRNA SNPs in patients undergoing radiation therapy for soft tissue sarcoma and anti-PD1 immunotherapy. Results suggest that mirSNPs can predict major wound toxicity, late toxicity, distant metastases, and pathological response to radiation, as well as immune-related adverse events (irAEs) from anti-PD1 therapy. This platform offers a novel approach for personalizing cancer treatment by identifying patients at increased risk for adverse events and predicting treatment response, ultimately improving patient outcomes and quality of life.
Key Highlights
- Two studies accepted for presentation at ASCO 2025 highlight MiraDx's mirSNP platform.
- The platform predicts treatment-related toxicity and response to cancer therapies.
- Studies show mirSNPs predict outcomes in soft tissue sarcoma radiation therapy and anti-PD1 immunotherapy.
- This approach enables personalized cancer treatment by improving safety and efficacy.
Emerging Mechanism of Action
Emerging Mechanisms of Action for Cancer Treatment
Key Emerging Mechanisms
The Hippo pathway has emerged as a crucial signaling mechanism in cancer development. This pathway normally inhibits cell growth, with YAP/TAZ transcriptional coactivators serving as key components. When the Hippo pathway is inhibited, YAP/TAZ localize in the nucleus and induce expression of genes related to cell proliferation. Dysregulation of this pathway can lead to various cancers. Understanding Hippo pathway mechanisms, particularly YAP/TAZ nuclear localization, may lead to identification of new therapeutic targets for cancer treatment.
Novel Therapeutic Approaches
Several innovative treatment modalities are showing promise:
- Photothermal and sonodynamic therapy using sensitizers activated by light/ultrasound radiation
- Black-titanium nanoparticle functionalized with iridium complexes and cancer cell membranes for targeted cancer imaging and therapy
- These nanoparticles generate heat upon irradiation and catalytically form reactive oxygen species upon ultrasound radiation
- The nanoparticles selectively localize in mitochondria and preferentially accumulate in cancerous cells and tumors
Histone Deacetylase Inhibitors (HDACi)
HDACi demonstrate complex effects in cancer treatment:
- HDACi induce cell death but simultaneously activate tumor-progressive genes
- Cell migration activity was enhanced by HDACi treatments in 13 of 30 human breast, gastric, liver, and lung cancer cell lines
- Tumor metastasis was enhanced in HDACi-treated mice
- HDACi treatments activated multiple PKCs and downstream substrates
Combined Treatment Approaches
Combination therapies are showing significant potential:
- HDACi combined with PKC inhibitory agents (curcumin or tamoxifen) suppressed HDACi-activated tumor progressive proteins and cell migration in vitro
- These combinations also inhibited tumor growth and metastasis in vivo
- Targeting both tumorigenesis and HDACi-activated metastasis with low toxic modalities could develop new strategies for long-term cancer therapy
Targeting Redox Metabolism
Compounds targeting cellular redox systems demonstrate promise:
- RDC11 (a cycloruthenated compound) induces higher cytotoxicity than oxaliplatin in gastric cancer cells
- RDC11 targets glutathione (GSH) metabolism, which is an important drug resistance mechanism
- Cycloruthenated complexes regulate enzymes of the transsulfuration pathway via the Unfolded Protein Response (UPR) and its effector ATF4
- RDC11 induces expression of SLC7A11 encoding for the cystine/glutamate antiporter xCT
Cancer-Specific Approaches
For breast cancer specifically: - EGFR tyrosine kinase inhibitors (TKIs) showed little activity as single agents - EGFR TKIs may be useful in specific subgroups such as estrogen receptor positive (ER+), tamoxifen resistant patients - Blocking multiple growth promoting pathways simultaneously may be needed for effective treatment
Emerging End Points
Based on publications in PubMed over the past 3 years, several key emerging endpoints for cancer are evident:
Emerging Cancer Endpoints
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Synthetic lethal interactions have been identified as key cancer drug targets, focusing on:
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Proteins that are frequently mutated but difficult to inhibit pharmacologically (e.g., RAS)
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Proteins lost in cancer cells (e.g., tumor suppressor genes p53, APC, RB)
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Tumor Mutational Burden (TMB) has emerged as an important predictive biomarker for immune checkpoint inhibitors across multiple cancer types
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Chemotherapy was shown to increase TMB, especially in cancer types with lower treatment-naïve TMB (breast, prostate, and pediatric cancers)
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Post-chemotherapy TMB calculation may better predict immunotherapy response, particularly for tumors with initially low TMB
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TRAIL sensitivity (tumor necrosis factor-related apoptosis-inducing ligand) in cancer cells increases when combined with sorafenib (which down-regulates Mcl-1 protein)
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Prostaglandin E2 (PGE2) impacts Natural Killer (NK) cell anti-tumor functions by:
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Altering expression of activating receptors
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Reducing degranulation and cancer cell killing ability
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Modifying chemokine receptor expression on NK cells (inhibiting CXCR3, increasing CXCR4) affecting their migration patterns
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FAK (focal adhesion kinase) inhibition combined with gemcitabine and immune-checkpoint therapy shows promising results in pancreatic ductal adenocarcinoma (PDAC) mouse models
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Adjuvant chemotherapy improved survival in patients with completely resected T2N0M0 NSCLC across all tumor size groups, including those with tumors smaller than 4 cm
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Women with Neurofibromatosis type 1 (NF1) under 50 years old have a five-fold increased risk of breast cancer, present with more advanced disease, and may have increased breast cancer-related mortality
These emerging endpoints reflect the evolving landscape of cancer research, with increased focus on molecular targets, immune system interactions, and personalized treatment approaches based on specific biomarkers and genetic profiles.
MoA used in other indications
Based on the provided context, there is no information available about trials of radiation therapy and anti-PD1 therapy for indications other than cancer.
While the context mentions that PD-1 has an immunosuppressive role in both the tumor microenvironment and autoimmune diseases, it does not detail any clinical trials for non-cancer indications.
The only related information indicates that "rapid development is ongoing for kinase-targeted therapies in a broad array of indications" including: - Inflammatory diseases - Ophthalmology - Analgesia - Central nervous system (CNS) disorders - Complications of diabetes - Osteoporosis - Otology
However, this information does not specifically refer to anti-PD1 therapy trials in these areas, nor does it provide any intervention models for such trials.
The context provides extensive information about intervention models for various cancer-related trials, but no information about intervention models for radiation therapy or anti-PD1 therapy in non-cancer indications.