Inhibition of AXL and VEGF-A Has Improved Therapeutic Efficacy in Uterine Serous Cancer

Toboni, Michael D.; Lomonosova, Elena; Bruce, Shaina F.; Tankou, Joan; Mullen, Mary M.; Schab, Angela; Oplt, Alyssa; Noia, Hollie; Wilke, Danny; Kuroki, Lindsay M.; Hagemann, Andrea R.; McCourt, Carolyn K.; Thaker, Premal H.; Powell, Matthew A.; Khabele, Dineo; Mutch, David G.; Fuh, Katherine C.

doi:10.3390/cancers13235877

Cited by 4 publications

(2 citation statements)

References 52 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These assays were performed with HUVECs, which were cultured following the method described earlier. The protocols for angiogenesis invasion and tube-forming assays were carried out on HUVECs with slight modifications as described in a previous study [ 32 ]. The analysis of angiogenesis invasion assay followed the same procedure as the trans-well and invasion assays mentioned earlier.…”

Section: Methodsmentioning

confidence: 99%

Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma

Matoba,

Zarrella,

Pooladanda

et al. 2024

Br J Cancer

View full text Add to dashboard Cite

Background Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3’s role in promoting USC pathology is lacking. Methods We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3’s impact on cell function. Results TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids. Conclusion These findings suggest inhibiting Gal3 may benefit USC patients.

show abstract

Section: Methodsmentioning

confidence: 99%

Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma

Matoba,

Zarrella,

Pooladanda

et al. 2024

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Cabozantinib is a tyrosine kinase inhibitor that works by blocking the activity of certain proteins involved in the growth and spread of cancer cells, including VEGFR, MET, and AXL. In endometrial cancer, over-expression of these proteins is associated with poor prognosis and resistance to standard treatments [45]. The combination of cabozantinib and immunotherapy has shown promise in the treatment of certain types of cancer, including advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) [46][47][48].…”

Section: Vegf Inhibitorsmentioning

confidence: 99%

Dostarlimab as a promising immunotherapy for endometrial cancer treatment – literature review

Derlatka,

Tasior,

Kulczycka

et al. 2023

J Pre Clin Clin Res.

View full text Add to dashboard Cite

Introduction and Objective. Endometrial cancer, a leading gynecological malignancy, is on the rise globally. Existing treatments for advanced cases have limited effectiveness and notable side-effects. Dostarlimab, a monoclonal antibody, enhances the immune response against tumuors by blocking the PD-1/PD-L1/PD-L2 interaction. This review examines dostarlimab's role, mechanism, clinical trials, and safety in endometrial cancer. Review Methods. A search was conducted using PubMed and Google Scholar databases to evaluate dostarlimab's therapeutic potential in endometrial cancer. The review encompasses studies detailing its mechanism of action, clinical trial outcomes, and safety data. Brief description of the state of knowledge. Endometrial cancer, the foremost gynecological malignancy in developed countries, has seen a surge in global incidence. Traditional treatments for advanced or recurrent cases exhibit limited efficacy and notable toxicity. Dostarlimab, an innovative monoclonal antibody, intervenes in the PD-1/PD-L1/PD-L2 axis, augmenting anti-tumour immune responses and fostering tumour regression. In April 2021, accelerated FDA approval was granted for dostarlimab in mismatch repair deficient recurrent or advanced endometrial cancer, post-platinum regimen. Subsequently, on 9 February 2023, FDA approval was extended to a broader patient cohort, encompassing those ineligible for curative surgery or radiation. Summary. Dostarlimab, targeting PD-1/PD-L1/PD-L2, shows promise in treating advanced endometrial cancer. Mechanism, trials, and safety are explored. FDA approvals highlight its potential. Ongoing trials and combination therapies suggest a dynamic role in management. Dostarlimab offers renewed hope for patients.

show abstract

TAM family kinases as therapeutic targets at the interface of cancer and immunity

DeRyckere,

Huelse,

Earp

et al. 2023

Nat Rev Clin Oncol

View full text Add to dashboard Cite

Inhibition of AXL and VEGF-A Has Improved Therapeutic Efficacy in Uterine Serous Cancer

Cited by 4 publications

References 52 publications

Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma

Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma

Dostarlimab as a promising immunotherapy for endometrial cancer treatment – literature review

TAM family kinases as therapeutic targets at the interface of cancer and immunity

Contact Info

Product

Resources

About