SMIP34 / Evestra, UT Health Science Center - LARVOL DELTA

Pelp1 inhibition disrupts dna repair and enhances topoisomerase inhibitor efficacy in triple negative breast cancer (SABCS 2025) - "These findings highlight PELP1 as a critical modulator of DNA damage response in TNBC and support the development of combination strategies using SMIP34 and topoisomerase inhibitors. This approach offers a promising therapeutic avenue for improving outcomes in patients with TNBC."

Clinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • BRCA1 • CDKN1A • CHEK1 • CHEK2 • PELP1

PELP1 oncogene targeted therapy for the treatment of ovarian cancer (AACR 2025) - "SMIP34 markedly diminished the viability of OCa cells resistant to carboplatin, cisplatin, and taxol. Collectively our results using in vitro, ex vivo, and in vivo models suggest that SMIP34 may serve as potential therapeutic for treating OCa by inhibiting PELP1 oncogenic signaling."

Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • ANXA5 • CASP3 • CASP7 • PELP1 • SENP3

Inhibiting PELP1 signaling enhances the therapeutic effectiveness of topoisomerase inhibitors in triple-negative breast cancer (AACR 2025) - "Collectively, these findings establish a robust preclinical foundation for the development of PELP1-targeted combination strategies for the treatment of TNBC."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • PELP1

PELP1 is a novel therapeutic target in hepatocellular carcinoma. (PubMed, Cancer Res Commun) - "Importantly, SMIP34, a first-in-class small molecule inhibitor targeting PELP1, effectively decreased the cell viability, clonogenic survival and invasiveness of HCC cells...Further, the knockdown or pharmacological inhibition of PELP1 significantly decelerated the HCC tumor growth in xenograft models. In summary, our study findings indicate that PELP1 could serve as a promising target for therapeutic intervention in HCC."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • MYC • PELP1

Significance of PELP1 signaling in liver cancer progression (AACR 2024) - "Overall, the results of our study point to PELP1 as a potential therapeutic target for HCC intervention."

Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • PELP1

PELP1 inhibition enhances the therapeutic efficacy of topoisomerase inhibitors in triple-negative breast cancer (AACR 2024) - "Of the five drugs, the three drugs Gemcitabine, Valrubicin, and Mitoxantrone, induced DNA damage by inhibiting topoisomerase, a protein that cleaves and reconnects DNA during replication. Together, these results suggest a novel targeted therapy for the treatment of TNBC, involving the combination of topoisomerase inhibitors and the PELP1 inhibitor SMIP34."

Clinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • PELP1 • TOP2A

Small molecule inhibitor of PELP1 exhibit cytotoxic effects on breast cancer cells by blocking ribosome biogenesis (SABCS 2023) - "These findings provide solid evidence that the Rix1 complex, which is required for ribosomes production, is disturbed by SMIP34 binding to PELP1. SMIP34 represents a new therapeutic for the treatment of both ER+ and TNBC breast cancer. Supported by VA grant 1 I01 BX004545-01A1."

Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • PELP1 • RPS6

PELP1 inhibition by SMIP34 reduces endometrial cancer progression via attenuation of ribosomal biogenesis. (PubMed, Mol Oncol) - "Importantly, SMIP34 treatment resulted in a significant reduction of the growth of ECa xenografts. Collectively, these findings underscore the potential of SMIP34 in treating ECa."

Journal • Endometrial Cancer • Oncology • Solid Tumor • PELP1

Targeting PELP1 oncogenic signaling in TNBC with the small molecule inhibitor SMIP34. (PubMed, Breast Cancer Res Treat) - "Together, these findings from in vitro, ex vivo, and in vivo models show that SMIP34 may be a useful therapeutic agent for inhibiting PELP1 signaling in TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • EIF4EBP1 • LAS1L • MYC • PELP1

The role of PELP1 inhibitor SMIP34 in the treatment of endometrial cancer (AACR 2023) - "Response rates and progression free survival are still low for recurrent ECa treatments such as hormone therapy, chemotherapy, and targeted therapies like Bevacizumab and Everolimus. Collectively, our results suggest that SMIP34 inhibits ECa growth in vitro, in vivo, and ex vivo and combination of SMIP34 with mTOR inhibitor represents a novel therapeutic strategy for ECa."

Endometrial Cancer • Oncology • Solid Tumor • ANXA5 • LAS1L • PELP1