Additionally, the AXL inhibitor Bemcentinib effectively inhibited the proliferation organoids and enhanced the immunotherapeutic efficacy of Atezolizumab. Furthermore, neural crest-like cells were observed in the glial reactive tissue surrounding finger-like protrusions. Overall, our results revealed that the AXL might be a potentially effective therapeutic target for ACPs.

The objective of this study is to assess the anti-cancer efficacy of trichostatin C (TSC), an analogue of trichostatin A sourced from the fermentation of Streptomyces sp...When combined with the DNMT inhibitor decitabine, TSC exhibits a synergistic anti-cancer effect...In conclusion, our findings suggest TSC as a promising anti-cancer agent with HDAC inhibitory activity. Furthermore, our results highlight the potential utility of TSC in combination with DNMT inhibitors for cancer treatment.

P1, N=67, Active, not recruiting, Pfizer | Trial completion date: Feb 2024 --> Jun 2024 | Trial primary completion date: Feb 2024 --> Jun 2024

Its target engagement and selectivity were also confirmed by NanoBRET and cell-based MERTK and AXL phosphorylation assays. Compound 43 had excellent pharmacokinetic properties (large AUC and long half-life) and mediated antitumor activity against lung cancer cell lines, indicating its potential as a therapeutic agent.

P1, N=12, Not yet recruiting, University of Wisconsin, Madison

Instead, pharmacological blockade with the AXL inhibitors bemcentinib (BGB324), cabozantinib and NPS-1034 rapidly killed RMS cells in an AXL-independent manner, and augmented the efficacy of the chemotherapeutics vincristine and cyclophosphamide. In vivo administration of the combination of bemcentinib and vincristine exerted strong anti-tumoral activity in a rapidly progressing PDX mouse model, significantly reducing tumor bruden compared to single-agent treatment. Collectively, our data identify bemcentinib as a promising drug to improve chemotherapy efficacy in RMS patients.

P1/2, N=120, Recruiting, Qurient Co., Ltd. | Phase classification: P1b/2 --> P1/2

P3, N=490, Recruiting, Beijing Konruns Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg-1·d-1) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg-1·d-1) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients.

Glesatinib had an acceptable safety profile in patients with advanced, pre-treated NSCLC with MET activating alterations. Modest clinical activity was observed, which likely reflects suboptimal drug bioavailability suggested by previously reported Phase I data, and pharmacodynamic findings of lower than anticipated increases in circulating soluble shed MET ectodomain (s-MET).

P1, N=23, Completed, University of Texas Southwestern Medical Center | Active, not recruiting --> Completed | Trial completion date: May 2027 --> Apr 2023

P1, N=36, Active, not recruiting, Oscotec Inc. | Recruiting --> Active, not recruiting

P1, N=14, Completed, Oscotec Inc. | Unknown status --> Completed | N=40 --> 14

P1, N=32, Completed, Arcus Biosciences, Inc. | Recruiting --> Completed

P1, N=10, Terminated, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=20 --> 10 | Suspended --> Terminated; NCI decided to terminate ABTC Consortium due to NCI moving in different direction for Brain Cancer - official close date is 10/31/23

P1, N=80, Recruiting, Arcus Biosciences, Inc. | Not yet recruiting --> Recruiting

P1, N=36, Not yet recruiting, Washington University School of Medicine | Trial completion date: Aug 2033 --> Nov 2033 | Initiation date: Dec 2023 --> Mar 2024 | Trial primary completion date: Aug 2028 --> Nov 2028

Thus, TP-0903 and ZEB1 knockdown sensitised TNBC cells to ART, likely via different pathways. Synergistic interactions between TP-0903 and ART indicate that combination approaches involving these compounds can have therapeutic prospects for TNBC treatment.

P3, N=490, Not yet recruiting, Beijing Konruns Pharmaceutical Co., Ltd.

P1, N=78, Recruiting, Qurient Co., Ltd. | Trial completion date: Nov 2023 --> Feb 2025 | Trial primary completion date: Jul 2023 --> Dec 2024

P1/2, N=12, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P1/2, N=12, Active, not recruiting, M.D. Anderson Cancer Center | N=19 --> 12

Most importantly, Hit-3 exhibited significant in vivo antitumor efficacy in xenograft models. Collectively, this study is the first discovery of dual-targeting AXL/HDAC2 inhibitors for colorectal cancer treatment.

P1, N=84, Active, not recruiting, Incyte Corporation | Phase classification: P1a/1b --> P1 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Nov 2023 --> Nov 2024

P1, N=20, Suspended, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2024 --> Dec 2023

More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

P1/2, N=98, Recruiting, SignalChem Lifesciences Corporation | Phase classification: P1b/2 --> P1/2

P1, N=177, Completed, Sumitomo Pharma America, Inc. | Phase classification: P1a --> P1

P1, N=80, Not yet recruiting, Arcus Biosciences, Inc.

At variant level, PIK3CA p.H1047R (22%) and RBM26 p.Q701Tfs*23 (10%) were the top two somatic variants identified...Conclusions ctDNA status and dynamics correlate well with clinical status of patients with mILC, as determined by conventional monitoring tools such as imaging and biopsy. Our results indicate that personalized, tumor-informed, longitudinal ctDNA testing may serve as a useful tool for detection of progression and monitoring treatment response in mILC patients.

Such patients benefit from hypomethylating agents and venetoclax but frequently develop resistance to this treatment regimen. Additionally, extended research on TNFα and cytotoxic immune cells may lead to a better understanding of what mechanisms cause a treatment response. This may ultimately enable an accurate selection of patients who will benefit from bemcentinib-LDAC.

P1, N=36, Not yet recruiting, Washington University School of Medicine | Trial completion date: Apr 2033 --> Aug 2033 | Initiation date: Sep 2023 --> Dec 2023 | Trial primary completion date: May 2028 --> Aug 2028

P1b/2, N=72, Terminated, Aravive, Inc. | Trial completion date: Mar 2025 --> Aug 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Aug 2023; Due to business reasons

P3, N=366, Terminated, Aravive, Inc. | There was no detriment to overall survival. No new safety signals were identified.

P1b/2, N=34, Terminated, Aravive, Inc. | N=99 --> 34 | Trial completion date: Oct 2025 --> Aug 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2024 --> Aug 2023; Due to business reasons

P1, N=32, Recruiting, Arcus Biosciences, Inc. | Not yet recruiting --> Recruiting

P1, N=19, Active, not recruiting, University of Oklahoma | Trial primary completion date: Aug 2023 --> Jan 2024

P1, N=12, Completed, Beijing Konruns Pharmaceutical Co., Ltd. | Active, not recruiting --> Completed

P1, N=20, Suspended, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Suspended

We also found that AXL-STAT3 inhibition can impede the recruitment of TAMs in a xenograft mouse model, thereby suppressing tumor growth. These findings suggest the potential application of AXL-STAT3-related markers to quantitatively assess metastatic potential and inform therapeutic strategies in lung cancer.

P1, N=24, Completed, Ono Pharmaceutical Co. Ltd | Suspended --> Completed | N=84 --> 24 | Trial completion date: Apr 2023 --> Nov 2022