sapitinib (AZD8931) / AstraZeneca - LARVOL DELTA

A Riskscore Model for Predicting Survival, Tumor Microenvironment, Immunotherapy and Drug Sensitivity of Lung Squamous Cell Carcinoma Based on PI3K/AKT/MTOR Pathway-Related Genes. (PubMed, J Environ Pathol Toxicol Oncol) - "LR group had lower TIDE scores and lower IC50 values (Alpelisib, Ibrutinib, Sapitinib, and Savolitinib). Patients in LR group had potential advantages in survival, immune response, and drug sensitivity. In summary, the results offered new insights into prognosis prediction, immunotherapy, and personalized treatment of LUSC."

Biomarker • Journal • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma • CAB39 • CDKN1A • TRIB3

Identification and validation of prognostic genes associated with mitochondrial nuclear genes in gastric cancer. (PubMed, Clin Exp Med) - "BMS-754807, Gefitinib, JQ1, Lapatinib, and Sapitinib exhibited significant differences in sensitivity between the high-risk group and the low-risk group. The results of molecular docking showed TP8A2 has stable binding ability with cytosine, COX15 with indomethacin, and TARS2 with bisacodyl. RT-qPCR revealed downregulation of ATP8A2 and upregulation of COX15 and TARS2 in GC samples. MNGs, including ATP8A2, COX15, and TARS2, demonstrated significant associations with immune infiltration, CNV, and prognostic outcomes of GC."

Biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor

Immunogenic cell death-related genes as prognostic biomarkers and therapeutic insights in uterine corpus endometrial carcinoma: an integrative bioinformatics analysis. (PubMed, Front Oncol) - "Finally, we found that hyper-immunogenicity may be sensitive to immunotherapy and certain drugs (AZD5991, Ibrutinib, Osimertinib, AGI-5198, Savolitinib, Sapitinib, AZ960, AZD3759 and Ruxolitinib), while PCI-34051 and Vorinostat showed sensitivity in patients with hypo-immunogenicity. Our results demonstrate that ICD plays an important role in UCEC progression, suggesting that ICD-related markers could serve as potential targets for prognosis and treatment."

Biomarker • IO biomarker • Journal • Tumor mutational burden • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer • CD52 • STAT1 • TMB

Identification of anoikis-related genes to develop a risk model and predict the prognosis and tumor microenvironment in rectal adenocarcinoma. (PubMed, Front Genet) - "Drug sensitivity analysis revealed differences in the IC50 values of OSI-027, PLX-4720, UMI-77, and Sapitinib between the high-risk and low-risk groups. Enrichment analysis revealed that these prognostic ARGs were primarily enriched in pathways and biological processes related to tumorigenesis. The risk model of ARGs can effectively predict READ prognosis and provide potential therapeutic targets."

Biomarker • Journal • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Solid Tumor • ALDH1A1 • BRCA1 • KRT17

Multi-Omics Integration: Predicting Progression and Optimizing Clinical Treatment of Hepatocellular Carcinoma Through Malignant-Cell-Related Genes. (PubMed, Int J Mol Sci) - "Risk stratification based on these signatures revealed distinct therapeutic vulnerabilities: high-risk patients showed increased sensitivity to sorafenib, while low-risk patients exhibited enhanced responses to immunotherapy and transarterial chemoembolization (TACE). Pharmacogenomic analysis with Oncopredict identified four chemotherapeutic agents, including sapitinib and dinaciclib, with risk-dependent efficacy patterns. Furthermore, CRISPR/Cas9-dependency screening prioritized SRSF7 as essential for HCC cell survival, a finding confirmed by the identification of protein-level overexpression in tumors via immunohistochemistry. This multi-omics framework bridges single-cell characterization to clinical decision-making, offering a clinically actionable prognostic system that can be used to optimize therapeutic selection in HCC management."

Biomarker • IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • SRSF7

Multi‑cohort Validation Based on Disulfidptosis-Related lncRNAs for Predicting Prognosis and Immunotherapy Response of Esophageal Squamous Cell Carcinoma. (PubMed, Onco Targets Ther) - "Additionally, individuals at high risk showed higher sensitivity to erlotinib, acetalax, gefitinib, lapatinib, sapitinib, and afatinib. Nevertheless, this study is retrospective and relies on public databases, with a limited sample size within the datasets. In the future, it is essential to conduct more extensive validation of the prognostic value and efficacy in real ESCC cohorts."

IO biomarker • Journal • Tumor mutational burden • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • TMB

Co-targeting the HER family and mutant KRAS is efficacious in colorectal cancer (AACR 2025) - "We have found that there is a striking increase in total HER3 levels in SNU-407, LS180, LS513 cells and 572918-348-R and 172845-121-B patient derived organoids (PDOs) when treated with the KRASG12D inhibitorsMRTX1133 and RMC9805, creating an adaptive response that could limit the efficacy of a KRAS inhibitor as a single agent...Co-targeting EGFR and mutant KRAS resulted in a slight synergistic effect in KRASG12D mutant cell lines usingMRTX1133 in combination with sapitinib, afatinib or peltinib. Currently, we are assessing if there is a synergistic effect directly targeting HER3 with a HER3 antibody-drug-conjugate in combination with a KRAS inhibitor in CRC cells. Our findings may present a new paradigm for targeted combination therapies in colorectal cancer with the eventual goal of increased overall patient survival."

Colorectal Cancer • Oncology • Solid Tumor • EGFR • ERBB4 • HER-2 • KRAS

Identification of the clinical value and biological effects of TTN mutation in liver cancer. (PubMed, Mol Med Rep) - "The OncoPredict algorithm and CCK‑8 assays revealed that TTN mutations are associated with altered drug sensitivity, particularly to GSK1904529A, nilotinib, 5‑fluorouracil (5‑FU) and sapitinib. The findings indicated that TTN mutations increase protein stability and lower intracellular ferrous ion levels, thereby suppressing ferroptosis and contributing to resistance to 5‑FU in hepatoma cells. These results suggest that TTN mutations are associated with poor prognosis in liver cancer and could serve as a predictive biomarker for liver cancer progression, prognosis and drug resistance."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Transplantation • TTN

Identification and validation of an m5C-related lncRNA signature for predicting prognosis and immune response in clear cell renal cell carcinoma. (PubMed, Discov Oncol) - "The model also predicted the sensitivity of drugs, including Entinostat, SB216763, and Sapitinib. Overall, these findings suggest that the 9 m5C-related lncRNAs can accurately predict ccRCC patient prognosis, providing potential applications for clinical and immunotherapy approaches. GNG12-AS1 emerges as a promising prognostic biomarker for predicting survival outcomes in ccRCC, potentially influencing cell migration through the activation of the ERK/GSK-3β/β-catenin signaling pathway."

IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Dec 2024 ➔ Dec 2025

IO biomarker • Trial completion date • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

ARID2 Deficiency Enhances Tumor Progression via ERBB3 Signaling in TFE3-Rearranged Renal Cell Carcinoma. (PubMed, Curr Issues Mol Biol) - "TFE3-RCC ARID2 KO cells demonstrated heightened sensitivity to the ERBB3 inhibitor AZD8931 compared to their wild-type counterparts, exhibiting significantly reduced migration and proliferation rates. These findings suggest that the PRCC-TFE3-ARID2-ERBB3 axis plays a critical role in TFE3-RCC pathogenesis and highlights the potential of targeting ERBB3 in ARID2-deficient TFE3-RCC as a therapeutic strategy. This study provides new insights into the molecular mechanisms of TFE3-RCC and suggests avenues for precision treatment of this aggressive cancer."

Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • ARID2 • EGFR • ERBB3 • PRCC • TFE3

Immune microenvironment modulation following neoadjuvant therapy for oesophageal adenocarcinoma: a translational analysis of the DEBIOC clinical trial. (PubMed, ESMO Open) - "OAC may be subdivided into three immune-related subgroups which undergo modulation in response to neoadjuvant therapy with marked suppression of the immune microenvironment in HER2-positive/immune-high tumours."

Journal • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

FOXN3-AS1: A Candidate Prognostic Marker and Epigenetic Target with Immunotherapeutic Implications in Acute Myeloid Leukemia. (PubMed, Curr Med Chem) - "Our candidate approach identifies FOXN3-AS1 as a prognostic indicator of survival in AML with a potential immune-related role. The preliminary observations we made on FOXN3-AS1/DNMT1 crosstalk warrant more in-depth invested immunotherapeutic approaches in AML."

Biomarker • IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • GLI2

Copper metabolism-related signature for prognosis prediction and MMP13 served as malignant factor for breast cancer. (PubMed, Heliyon) - "Patients with higher CuScores had lower TMB and were more sensitive to Sapitinib and LCL161, while those with lower CuScores might respond better to anti-PD1 therapy. The identified copper metabolism-related gene signature has the potential to predict prognosis and guide clinical treatment for BC. Among these genes, MMP13 may act as a malignant factor in BC."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • ATP7A • CEACAM5 • MAPK1 • MMP13 • SLC31A1 • UBE2D2

Machine learning-based disulfidptosis-related lncRNA signature predicts prognosis, immune infiltration and drug sensitivity in hepatocellular carcinoma. (PubMed, Sci Rep) - "Additionally, the high-risk group exhibited higher sensitivity to Afatinib, Fulvestrant, Gefitinib, Osimertinib, Sapitinib, and Taselisib. In conclusion, our study highlighted the potential utility of the constructed DRLPS in the prognosis prediction of HCC patients, which demonstrated promising clinical application value."

IO biomarker • Journal • Machine learning • Cognitive Disorders • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • ZNF23

Bulk and single-cell sequencing identified a prognostic model based on the macrophage and lipid metabolism related signatures for osteosarcoma patients. (PubMed, Heliyon) - "Finally, our meticulous drug sensitivity analysis identified a spectrum of potential therapeutic agents for OS, including AZD2014, Sapitinib, Buparlisib, Afuresertib, MIRA-1, and BIBR-1532. These findings significantly augment the therapeutic arsenal available to clinicians managing OS, presenting a promising avenue for elevating treatment outcomes."

Journal • Metabolic Disorders • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Comparison of trastuzumab emtansine, trastuzumab deruxtecan, and disitamab vedotin in a multiresistant HER2-positive breast cancer lung metastasis model. (PubMed, Clin Exp Metastasis) - "L-JIMT-1 cells were resistant to all five tyrosine kinase inhibitors tested in vitro (afatinib, erlotinib, lapatinib, sapitinib, and tucatinib). In a mouse model, all three ADCs inhibited the growth of L-JIMT-1 lung metastases compared to a vehicle, but DV and T-DXd more strongly than T-DM1, and DV treatment led to the smallest tumor burden. The L-JIMT breast cancer lung metastasis model developed may be useful in the evaluation of anti-cancer agents for multiresistant HER2-positive advanced breast cancer."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • HER-2

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Dec 2023 ➔ Dec 2024

IO biomarker • Metastases • Trial completion date • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor

SAFIR02_Lung - Efficacy of Targeted Drugs Guided by Genomic Profiles in Metastatic NSCLC Patients (clinicaltrials.gov) - P2 | N=999 | Completed | Sponsor: UNICANCER | Active, not recruiting ➔ Completed

IO biomarker • Metastases • Trial completion • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Identification of the novel markers of PPAR signalling affecting immune microenvironment and immunotherapy response of lung adenocarcinoma patients. (PubMed, J Cell Mol Med) - "Intriguingly, high-risk patients exhibited a potential heightened sensitivity to immunotherapy and certain drugs, including Gefitinib, Afatinib, Erlotinib, IAP_5620, Sapitinib, LCL161, Lapatinib and AZD3759. The prognosis model based on eight PPAR-related genes has satisfactory prognosis prediction efficiency. Meanwhile, our results can provide direction for future studies in the relevant aspects."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ACSL3 • FABP1

Inhibition of ErbB3 and Associated Regulatory Pathways Potently Impairs Malignant Peripheral Nerve Sheath Tumor Proliferation and Survival. (PubMed, Am J Pathol) - "Consistent with this, inhibition of upstream (canertinib, sapitinib, saracatinib, calmodulin) and parallel (AZD1208) signaling pathways involving MAPK and mTOR reduced MPNST proliferation and survival. Src inhibition (saracatinib), like erbB3 knockdown, prevents these phosphorylation events and when combined with trifluoperazine even more effectively reduces proliferation and survival compared to monotherapy. Our findings implicate erbB3, calmodulin, PIM kinases and Src family members as important therapeutic targets in MPNSTs and demonstrate that combinatorial therapies targeting critical MPNST signaling pathways are more effective."

Journal • Brain Cancer • Fibrosis • Genetic Disorders • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • ERBB3 • NRG1

Development of an LC-MS/MS Method for Quantification of Sapitinib in Human Liver Microsomes: In Silico and In Vitro Metabolic Stability Evaluation. (PubMed, Molecules) - "In multiple tumor cell lines, STP has been shown to be a much more potent inhibitor of EGF-driven cellular proliferation than gefitinib...SPT and filgotinib (FGT) (internal standard; IS) were separated through the use of an isocratic mobile phase system with a Luna 3 µm PFP(2) column (150 × 4.6 mm) stationary phase column...STP exhibited a moderate extraction ratio that revealed good bioavailability. The literature review demonstrated that the current analytical method is the first developed LC-MS/MS method for the quantification of SPT in an HLM matrix with application to SPT metabolic stability evaluation."

Journal • Preclinical • Oncology • EGFR

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Dec 2022 ➔ Dec 2023

IO biomarker • Metastases • Trial completion date • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • PD-L1

PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer. (PubMed, Br J Cancer) - P2 | "The combination of pulsed high-dose AZD8931 with FOLFIRI has acceptable toxicity. Further studies of TKI sequencing may establish a role for pulsed use of such agents rather than continuous exposure."

Journal • P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • HER-2

PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer (Br J Cancer, Nature) - P1/2 | N=24 | PANTHER (NCT01862003) | "This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931...combined with chemotherapy, in metastatic colorectal cancer (CRC)....Eighteen patients received FOLFIRI and AZD8931. At 160 mg bd, 1 patient experienced G3 DLT; 160 mg bd was used for cohort expansion. No grade 5 adverse events (AE) reported. Seven (39%) and 1 (6%) patients experienced grade 3 and grade 4 AEs, respectively. Of 12 patients receiving 160 mg bd, best overall response rate was 25%, median PFS and OS were 8.7 and 21.2 months, respectively."

P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor