dovitinib (TKI258) / Novartis, Oncoheroes - LARVOL DELTA

Orthotopic PDX modeling and preclinical therapeutic evaluation in pediatric ependymoma (EANO 2026) - "A targeted drug panel based on molecular alterations in ST-EPN, including CBL0137 (epigenetic inhibitor), ACT001 (NF-κB inhibitor), dovitinib and lenvatinib (VEGFR inhibitors), and entinostat and quisinostat (HDAC inhibitors) was evaluated for cytotoxicity in vitro using Alamar Blue and clonogenic assays. These orthotopic ST-EPN PDX models represent a reliable preclinical platform, enabling evaluation of molecularly guided combination therapies for pediatric ST-EPN with ZFTA-RELA fusion. Dovitinib emerged as a potential new treatment for RELA fused EPN."

Preclinical • Ependymoma • Oncology • Solid Tumor • RELA • ZFTA

Development of orthotopic PDX models and discovery of targeted therapies in pediatric ependymoma (ISPNO 2026) - "Targeted agents were selected based on molecular alterations in relapsed zccs1304 tumors and assessed for therapeutic efficacy, including FACT inhibitor (CBL0137), NF-κB inhibitor (ACT001), VEGFR inhibitors (dovitinib, lenvatinib) and HDAC inhibitors (entinostat, quisinostat). Additionally, dovitinib in combination with CBL0137 or quisinostat significantly enhanced cytotoxicity in cultures. Our orthotopic ST-EPN PDX models offer a reliable preclinical platform for developing rational combination therapies for pediatric ST-EPN with ZFTA-RELA fusion."

Clinical • Ependymoma • Oncology • Pediatrics • Solid Tumor • RELA • ZFTA

Multiple binding modes of the tyrosine kinase inhibitor dovitinib to fibroblast growth factor receptor 1 characterized by surface plasmon resonance, 19F-NMR, and molecular dynamics simulations. (PubMed, J Biochem) - "Furthermore, MD simulations introducing an additional dovitinib molecule to the FGFR1-dovitinib complex indicated the potential for weak and transient interactions in the preferred interaction regions on the FGFR1 surface. These findings highlight the multifaceted nature of kinase-inhibitor interactions and provide valuable biophysical insights that may contribute to future drug discovery efforts targeting receptor tyrosine kinases."

Journal • Oncology • FGFR1

Study of PARPi 2X-121 as Monotherapy and in Combination With Dovitinib in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=14 | Terminated | Sponsor: Allarity Therapeutics | N=40 ➔ 14 | Suspended ➔ Terminated; Sponsor decision.

Enrollment change • Monotherapy • Trial termination • Oncology • Solid Tumor

Integrin-targeting cyclic peptides suppress TGF-β1-driven EMT and invasion in third-generation EGFR-TKI-resistant NSCLC. (PubMed, Chem Biol Interact) - "Resistance to third-generation EGFR-TKIs such as naquotinib and osimertinib remains a major obstacle in the treatment of non-small cell lung cancer (NSCLC). Among the derivatives, cilengitide (R-8) most effectively suppressed vimentin expression and ERK1/2 phosphorylation. Combination treatment with dovitinib further enhanced the inhibition of migration and invasion, suggesting synergistic potential."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TGFB1 • VIM

EZH2-AR non-canonical axis activation in TKI-resistant RCC: Differential effects of lenvatinib and cabozantinib (AACR 2026) - "Consistently, AR expression is observed in RCC lines resistant to sunitinib, dovitinib, and lenvatinib, but not with cabozantinib treatment...Overall, our findings suggest that EZH2-dependent kinase reprogramming drives AR phosphorylation and activation, contributing to drug resistance to selective TKIs. Cabozantinibunique ability to bypass AR/EZH2 upregulation underscores the need to explore alternative resistance pathways."

Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • AR • EZH2

Targeting multivalent receptor tyrosine kinases to enhance the efficacy of anti-PD-1 immunotherapy in gastric cancer (AACR 2026) - "Our findings demonstrate that the combination of dovitinib and PD-1 blockade is significantly more effective than either treatment alone, as the two therapies synergistically remodel the TME beyond their direct cytotoxic effects. This synergy is achieved by increasing the infiltration of activated tumor-infiltrating lymphocytes (TILs) and reducing the exhaustion phenotype typically seen with monotherapy. This study supports the rationale for combining multi-target RTKs inhibitors with immunotherapies as an effective therapeutic strategy for gastric cancer."

Clinical • IO biomarker • Gastric Cancer • Oncology • Solid Tumor • CD4 • CD69 • CD8 • CTLA4

The antihistamine terfenadine inhibits TFE3 dimerization, has antitumor activity and synergizes with tyrosine kinase inhibitors in translocation renal cell carcinoma (AACR 2024) - "The combination of terfenadine with sunitinib showed a synergistic effect in cells endogenously expressing PRCC-TFE3 (IC50=1.5µM; Fraction Affected > 0.05) and NONO-TFE3 (IC50=1.8µM; Fraction Affected0.7). The combination of terfenadine with dovitinib showed a synergistic effect in cells expressing PRCC-TFE3 fusion (IC50=1µM; Fraction Affected>0.4)...This observation underlines the importance of identifying the TFE3 partner gene for targeted therapy. Overall, our results suggest that targeting the dimerization domain along with different oncogenic pathways activated in tRCC cells may represent a new therapeutic approach for this disease."

Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PRCC • TFE3 • TFEB

Exploring ZPLD1 as a Prognostic Indicator and Therapeutic Target in Bladder Cancer. (PubMed, Curr Med Chem) - "This study establishes ZPLD1 as a prognostic indicator and potential therapeutic target in BLCA, paving the way for precision oncology strategies integrating ZPLD1-guided patient selection and immune-drug combinations."

Biomarker • IO biomarker • Journal • Bladder Cancer • Genito-urinary Cancer • Inflammatory Arthritis • Oncology • Solid Tumor • Urethral Cancer • CTLA4 • LAG3 • PD-1 • PD-L1 • SIGLEC15

Combined treatment of TKIs with Cilengitide overcomes afatinib-resistance in EGFR-mutated NSCLC cells. (PubMed, Mol Biol Rep) - "Our findings demonstrate that cilengitide, a cyclic RGD peptide, effectively suppresses invasion and migration in afatinib-resistant NSCLC cells through inhibition of the integrin-FAK signaling axis. Although cilengitide showed limited growth inhibition as a monotherapy, its combination with TKIs such as afatinib or dovitinib significantly enhanced anti-proliferative and anti-invasive effects. These synergistic outcomes were associated with reduced expression of integrin-mediated proteins and MMPs, suggesting that cilengitide may potentiate TKI efficacy by modulating the tumor microenvironment and migratory potential of resistant cells. Taken together, this study supports the potential of cilengitide as an adjuvant therapeutic strategy in treating EGFR-TKI-resistant NSCLC. Further validation through preclinical animal models and pharmacokinetic studies will be crucial for future clinical translation."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDH2 • EGFR • TGFB1 • VIM • VTN

Ex Vivo Drug Sensitivity Evaluation of a ZMYM2: : FGFR1 Fusion-Positive 8p11 Myeloproliferative Syndrome (EMS) Leukemia (ASH 2023) - "Bortezomib and Axitinib exhibited high efficacy on the patient's sample...Other FGFR inhibitors, including Olverematinib, AZD4547, Axitinib, Cediranib, Dovitinib, and Lenvatinib, also demonstrated exquisite sensitivity. Despite extensive screening, no other single agents or drug combinations exhibited increased effectiveness in the ZMYM2: : FGFR1 transformed BaF3 cells except for Trametinib, a MEK inhibitor, and the combination of Belvarafenib (RAF inhibitor) and Gilteritinib (FLT3 inhibitor)... Ex vivo drug sensitivity assays demonstrated the highly selective efficacy of FGFR inhibitors in ZMYM2: : FGFR1 fusion-positive leukemia cells and a fusion-expressing BaF3 cell line. Mutations in the FGFR1 kinase domain (ZMYM2: : FGFR1 F1171L) could contribute to Ponatinib insensitivity. These ex vivo drug screening results provide further support for ongoing clinical trials which are investigating the use of single agent Pemigatinib and other FGFR1 inhibitors for the..."

Preclinical • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • FGFR1 • FLT3 • RUNX1 • ZMYM2

Integrating the secretome and interactome to identify novel biomarkers and therapeutic targets in colorectal cancer. (PubMed, Cell Commun Signal) - "This study highlights FGFR4, FLT1, and WNT5A as key diagnostic and therapeutic biomarkers for CRC, with their relevance varying based on the tumor's site of origin. Leveraging these findings, we propose Dovitinib and Nintedanib as promising targeted therapies for CRC. These insights can enhance current treatment strategies and pave the way for future in vivo and in vitro studies, driving progress in CRC research and therapy."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • FGFR4 • FLT1

Targeted therapies for Bacillus Calmette-Guerin unresponsive nonmuscle-invasive bladder cancer: a narrative review. (PubMed, Curr Opin Urol) - "The THOR-2 study demonstrated promising results for oral Erdafitinib in 73 high-risk BCG-unresponsive pTa/pT1 patients, showing 6 and 12-month recurrence-free survival rates of 96 and 77%, respectively. However, it was associated with notable adverse events (100%, including 22% serious). Other targeted therapies, such as Dovitinib (FGFR inhibitor), Sunitinib (VEGF inhibitor), and Everolimus (mTOR inhibitor), were assessed in three phase II studies, yielding disease-free survival rates between 8 and 44% over 3-12 months. Additionally, in a recent phase 3 trial involving 134 patients with BCG-unresponsive NMIBC, Oportuzumab Monatox (an EpCAM inhibitor) demonstrated a complete response rate of 40% at 3 months and a median response duration of 9.4 months."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance. (PubMed, Pharmaceutics) - "Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options,..."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Dovitinib Ameliorates Inflammation-Related Diseases by Inhibiting Necroptosis and Ferroptosis. (PubMed, ACS Chem Biol) - "Additionally, Dov inhibited ferroptosis by regulating the NRF2/HMOX1 axis and lipid peroxidation and protected against concanavalin A-induced acute liver injury. Thus, our work revealed that Dov is a dual inhibitor of necroptosis and ferroptosis and provides a potential therapeutic drug or combination approach for treating necroptosis- and ferroptosis-related diseases."

Journal • Hepatology • Immunology • Inflammation • Liver Failure • Oncology • Systemic Inflammatory Response Syndrome • HMOX1 • RIPK1 • TNFA

Molecular Docking and Drug-Likeness of Salicornia-Derived Phytochemicals Against HER Receptors. (PubMed, Curr Issues Mol Biol) - "Among them, 3,5-di-O-caffeoylquinic acid, 3-O-caffeoylquinic acid, myricetin, quercetin, stigmasterol, kaempferol, isorhamnetin, rhamnetin, and hesperitin featured strong predicted binding affinities to the HER1, HER2, and HER4 growth factor receptors, comparable to those of standard anti-cancer drugs such as gefitinib and dovitinib. Further pharmacokinetic assessments, including bioavailability and toxicity analyses, identified compounds with favorable drug-likeness properties and minimal toxicity risks, except for myricetin and quercetin. These findings underscore the potential of Salicornia-derived phytochemicals as promising candidates for the development of safe, novel, and effective anti-cancer agents targeting GFRs, contributing to the advances in precision oncology, pending further validation through in vitro and/or in vivo experiments."

Journal • Oncology • EGFR • ERBB4 • HER-2

Therapeutic targeting of triple-negative breast cancer: A multi-model evaluation of LNA-anti-miR-19b-3p and small molecule inhibitors. (PubMed, Comput Biol Med) - "Additionally, we screened for potential small molecule inhibitors, identifying four promising candidates, including Dovitinib, S-Adenosylmethionine, Guanosine-5',3'-tetraphosphate, and Neomycin, which exhibited favorable drug-like characteristics. In conclusion, our multifaceted approach demonstrates the significant potential of LNA-anti-miR-19b-3p as a therapeutic option for TNBC patients, and the small molecule inhibitors we've uncovered could open new avenues for treating this aggressive form of breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • FAT3 • GFOD1 • MIR19B1

Characterization of dovitinib-human serum albumin association potential through optical spectroscopic and in silico approaches. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Binding place of DTB, as detected by ligand displacement and molecular docking analyses, was found at Sudlow's site I in HSA. The results of the molecular dynamics simulations indicated that the DTB-HSA complex was stable."

Journal • Oncology

Differential Scanning Fluorimetry and compound screening enabled the identification of novel series of microRNA-21 targeting compounds (EACR 2025) - "Selectivity was proven by using as positive control dovitinib, a pre-miR-21 binding molecule that inhibits miR-21 biogenesis... The combination of DSF and screening has identified novel series of pharmacophores acting as pre-miR-21 binders, with the potential to serve as building blocks for the development of lead compounds offering an unconventional modality to target cancer progression."

Oncology • MIR21

IDENTIFICATION OF NOVEL THERAPEUTIC COMPOUNDS FOR THE TREATMENT OF INFANT PATIENTS WITH KMT2A-REARRANGED ACUTE LYMPHOBLASTIC LEUKEMIA BY DRUG REPURPOSING (EHA 2025) - "Additionally, synergistic effects with standard chemotherapy (Vincristine, Dexamethasone, L-Asparaginase; VXL) were assessed.The drug screening identified 119 compounds with selective activity against KMT2Ar iALL while sparing normal cells. This study successfully identified two RTKi as novel therapeutic candidates for KMT2Ar iALL through a drug repurposing approach. Dovitinib and Foretinib have a potent anti-leukemic activity, while sparing healthy cells. Their ability to synergize with standard chemotherapy highlights their potential for clinical application."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD34 • CDC37 • KMT2A

Study to Determine the Maximum Tolerated Dose (MTD) of PARPi 2X-121 Monotherapy and the MTD of Dovitinib in Combination With 2X-121 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=40 | Suspended | Sponsor: Allarity Therapeutics | Trial completion date: Mar 2025 ➔ Dec 2025

Monotherapy • Trial completion date • Oncology • Solid Tumor

FDA-approved drug repurposing screen identifies inhibitors of SARS-CoV-2 pseudovirus entry. (PubMed, Front Pharmacol) - "Pyridoxal 5'-phosphate, Dovitinib, Adefovir dipivoxil, and Biapenem potently inhibit ACE2-dependent viral entry with inhibitory concentration 50% (IC50) values of 57nM, 74 nM, 130 nM, and 183 nM, respectively. We identified four novel FDA-approved candidate drugs for anti-SARS-CoV-2 combination therapy. Our findings contribute to the growing body of evidence supporting drug repurposing as a viable strategy for rapidly developing COVID-19 treatments."

FDA event • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Allarity Therapeutics Announces Final Settlement with the U.S. Securities and Exchange Commission (GlobeNewswire) - "Allarity Therapeutics, Inc...today announced that it has reached a final settlement with the U.S. Securities and Exchange Commission (SEC) relating to the previously disclosed investigation regarding the Company’s past disclosures concerning its interactions with the U.S. Food and Drug Administration (FDA) regarding its New Drug Application ('NDA') for Dovitinib or Dovitinib-DRP, which was submitted to the FDA in 2021...Under the terms of the settlement, Allarity has consented, without admitting or denying the SEC’s findings, to the entry of an administrative cease-and-desist order. The settlement resolves the SEC’s investigation as to the Company with findings of violations of non-scienter-based provisions under Sections 17(a)(2) and (3) of the Securities Act of 1933, as well as Section 13(a) of the Securities Exchange Act of 1934 and related rules."

Commercial • Oncology • Solid Tumor

Health-related quality of life outcomes in hepatocellular carcinoma patients undergoing systemic therapies: a systematic review (AGW-GESA 2024) - "Eighteen (62%) studies assessed sorafenib and four (14%) studies assessed atezolizumab-bevacizumab (atezo-bev). Of the remaining studies, five (17%) studies investigated PD-1 inhibitors (three pembrolizumab, two nivolumab), two (7%) studied lenvatinib, two (7%) studied ramucirumab, and one study each evaluated cabozantinib, dovitinib, brivanib, regorafenib and durvalumab-tremelimumab... Despite worsening HRQOL outcomes compared to baseline, the first-line agents atezo-bev and lenvatinib improved HRQOL in comparison to sorafenib. Patients on PD-1 inhibitors or nivolumab experienced no change in HRQOL. Sorafenib significantly worsened HRQOL compared to TARE."

Clinical • HEOR • Review • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Study to Determine the Maximum Tolerated Dose (MTD) of PARPi 2X-121 Monotherapy and the MTD of Dovitinib in Combination With 2X-121 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=40 | Suspended | Sponsor: Allarity Therapeutics | Trial completion date: Dec 2024 ➔ Mar 2025 | Recruiting ➔ Suspended

Monotherapy • Trial completion date • Trial suspension • Oncology • Solid Tumor