Differences in correlations between RNA based measures of cell composition and immunohistologic quantification of infiltrates and extracted MRI parameters were observed for CIBERSORT, MCPcounter, and xCell methodologies. Based on these data, we hypothesize that the stromal radioresistant phenotype driven by TGFβ can be overcome by the addition of galunisertib to chemoradiation in rectal cancer.

Here, we evaluated targeting candidates from this signature KMT5B/C and IKBKE using inhibitors A-196 and IKBKEi respectively, alongside anti-estrogen (fulvestrant) and a TGFβ blocking antibody (NIS793), both individually and in combination with αPD-L1, within this rat model. Comprehensive tumor profiling through polychromatic flow cytometry and single-cell RNA sequencing revealed that A-196 induced a luminal-to-basal shift in tumor epithelial cells, enhancing antigen presentation, whereas epithelial-to-mesenchymal transition was linked to fulvestrant resistance. Our findings underscore the value of the rat mammary tumor model for preclinical studies in ER-positive breast cancer and advocate for the further validation and potential clinical development of KMT5B/C inhibitors to enhance the efficacy and broaden the applicability of ICI therapy in cancer patients.

TGFBR1 inhibition with galunisertib or senolytic treatment reduces tumor progression driven by cisplatin-induced senescence, and concomitant use of TGFBR1 inhibitors with platinum-based chemotherapy reduces tumor burden and improves survival. Finally, we validate the translational relevance of tumor-promoting TGFβ-enriched SASP using clinical NSCLC and HGSOC samples from patients who received neoadjuvant platinum-based chemotherapy. Together, our findings identify a potential cancer therapy resistance mechanism and provide preclinical proof of concept for future trials.

Selective blockade of latent TGF-β1 activation represents a promising approach for treating a broad range of fibrotic diseases and cancers. By specifically targeting TGF-β1, SOF10 may offer a safer and more effective therapeutic option compared to non-selective TGF-β inhibitors. This strategy has the potential to transform the treatment paradigm for fibrosis-related conditions.

STP355 also reduced tumor weight significantly, without the toxicity observed with cisplatin, resulting in prolonged survival of mice compared with this small molecule. It increased immune cell penetration into TME and reduced metastases to the lung. STP355 was more efficacious than, and somewhat additive with, immune checkpoint inhibitory monoclonal antibodies.

P2/3, N=167, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting | N=840 --> 167

These results demonstrate OS advantage for maintenance treatment of adult females with newly diagnosed, advanced stage IIIb-IV ovarian cancer with HRP status and cTMB-H profile who are in complete response after debulking surgery and frontline platinum-based doublet chemotherapy.

Biomarker data provide proof of mechanism and a potential ccRCC patient selection strategy. ClinicalTrials.gov identifier: NCT04291079 .

Instead, tranilast seems to indirectly suppress channel activation by reducing reactive oxygen species (ROS). This refined understanding of how tranilast modulates TRPV2 has important implications for the interpretation of prior and future pharmacological studies targeting TRPV2.

The PSMD14 inhibitor Capzimin exhibited potent anti-tumor effects in vitro and in vivo, and combination therapy with the TGF-β inhibitor galunisertib demonstrated enhanced efficacy...Consequently, the PSMD14-HMMR axis emerges as a promising therapeutic target. Inhibition of PSMD14 exhibited significant anti-tumor efficacy, underscoring its potential for clinical translation in LUAD treatment.

Our findings demonstrate that combination therapy targeting immune cells critical for antitumor responses and blocking immune-suppressive environment significantly improves antitumor therapeutic efficacy. These findings provide a strong basis for using HCW9218 to enhance the efficacy of ICIs against solid tumors in the clinical setting.

P2, N=60, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2026 --> Dec 2026