RITA / Aprea - LARVOL DELTA

Transient 18F-FDG PET/CT uptake of contralateral adrenal gland in patient under Mitotane for R0 corticosurrenaloma (ESPE-ESE 2025) - "S Leboulleux et al. Fluorodesoxyglucose uptake in the remaining adrenal glands during the follow-up of patients with adrenocortical carcinoma;EJE;01/2011.DOI:10.1530/EJE-10-0666."

Clinical • FDG PET • Adrenal Cortex Carcinoma • Cardiovascular • Dyslipidemia • Endocrine Disorders • Genito-urinary Cancer • Oncology • Solid Tumor • CYP11B1

Cr (VI) induces lactate utilization through HIF-1α/MCT1 dependent on p53 protein level. (PubMed, Food Chem Toxicol) - "CoCl2, an HIF-1α inducer, increased MCT1, while the HIF-1α inhibitor YC-1 and MCT1 inhibitor AZD3965 suppressed Cr (VI)-induced lactate utilization and cell growth...These findings highlighted the role of p53 protein level in the effects of Cr (VI) on HIF-1α/MCT1 to induce lactate utilization and cell growth. Targeting the p53/HIF-1α/MCT1 pathway could inhibit Cr (VI)-mediated tumorigenesis."

Journal • Oncology • HIF1A • SLC16A1

Artemisinin regulates cell proliferation, apoptosis, and the inflammatory response of human dental pulp stem cells through the p53 signaling pathway under LPS-induced inflammation. (PubMed, Int Immunopharmacol) - "This study demonstrates that ART facilitates the alleviation of inflammation and preserves the viability of HDPSCs. Therefore, ART may serve as a promising therapeutic drug for the repair and regeneration of dental pulp in the treatment of deep caries and reversible pulpitis."

Journal • Dental Disorders • Inflammation • CASP3

Primary neuroendocrine carcinoma of the prostate: a case series (ECP 2024) - "Primary NECa of the prostate, albeit being an extremely rare entity, can be seen in routine practice, either mixed with adenocarcinoma or in a pure form and is associated with low PSA levels, which may mislead the clinicians. Both NECa components are seen in the mixed cases and may show intraductal spread similarly to their adenocarcinoma counterparts. In contrast to therapy-related NECa, p53 frequently shows a wild-type pattern of expression and AR and PSA may be positive."

Clinical • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor

Astilbin Induces Apoptosis in Oral Squamous Cell Carcinoma through p53 Reactivation and Mdm-2 Inhibition. (PubMed, Dokl Biochem Biophys) - "This was followed by the induction of mitochondrial intrinsic apoptosis via the activation of caspases 9 and 3, cleavage of PARP, and the suppression of pro-apoptotic Bid. Astilbin-induced p53-mediated apoptosis in OSCC cells as herbal medicinal ingredients."

Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CASP9

MiR-34b promotes oxidative stress and induces cellular senescence through TWIST1 in human cervical cancer. (PubMed, Transl Oncol) - "MiR-34b promotes cellular senescence and oxidative stress by targeting TWIST1, a known oncogene and EMT regulator. This study delved into the mechanism of miR-34b-mediated tumor suppression and provided novel insights for development of miR-34b based therapeutics for cervical cancer."

Journal • Cervical Cancer • Oncology • Solid Tumor • MIR34B • TWIST1

Therapeutic targeting of ARID1A-deficient cancer cells with RITA (Reactivating p53 and inducing tumor apoptosis). (PubMed, Cell Death Dis) - "Taken together, ARID1A loss significantly heightens sensitivity to RITA in CRC, revealing a novel synthetic lethal interaction between ARID1A and RITA. These findings present a promising therapeutic approach for colorectal cancer characterized by ARID1A loss-of-function mutations."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ARID1A • CDKN1A • CHEK2

Sex Differences in Pulmonary Arterial Hypertension Traced to Sphingosine-1-Phosphate Dynamics (ATS 2024) - "Our results underscore that female pulmonary ECs, with a higher predisposition to apoptosis, release amplified S1P levels. Together with early alterations in the expression of S1P metabolic enzymes, specific to females, this upregulated S1P signaling axis could be a key determinant of the increased female predisposition to PAH."

Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CLU • S1PR1 • SGPP1

p53-dependent HIF-1α /autophagy mediated glycolysis to support Cr(VI)-induced cell growth and cell migration. (PubMed, Ecotoxicol Environ Saf) - "RITA, a p53 inducer, attenuated Cr(VI)-induced HIF-1α and LC3-II in A549 cells, suggesting that p53 might be the mechanism underlying the different effects of Cr(VI) on HIF-1α in A549 and HELF cells. Thus, p53-dependent HIF-1α / autophagy-mediated glycolysis plays a role in facilitating Cr(VI)-induced carcinogenesis."

Journal • Oncology • ATG4B • HIF1A

Mutant p53 gain-of-function stimulates canonical Wnt signaling via PI3K/AKT pathway in colon cancer. (PubMed, J Cell Commun Signal) - "We also found that while wt-p53 expression contributes to 5-FU sensitivity in colon cancer cells, the RITA p53 reactivating molecule counteracted the resistance against 5-FU in cells expressing mut-p53. Our results indicate that mut-p53 GOF acts as a positive regulator of canonical Wnt signaling and participates in the induction of resistance to 5-FU in colon cancer cells."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • TP53

RITA selectively inhibits proliferation of BAP1-deficient cutaneous melanoma cells in vitro (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations."

Journal • Preclinical • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • Targeted Protein Degradation • BAP1

Nucleolar phosphoprotein modifications as a marker of apoptosis induced by RITA treatment. (PubMed, Biochim Biophys Acta Mol Cell Res) - "Simultaneously, inverse changes occurred at Serine S4 of the NPM. These new findings of RITA mechanism of action could establish the NPM pT199/pS4 ratio as a marker for suitability of RITA treatment of AML cells."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • NCL • NPM1

Apatinib combined with olaparib induces ferroptosis via a p53-dependent manner in ovarian cancer. (PubMed, J Cancer Res Clin Oncol) - "This discovery revealed the specific mechanism of ferroptosis induced by apatinib combined with olaparib in p53 wild-type ovarian cancer cells and provided a theoretical basis for the clinical combined use of apatinib and olaparib in p53 wild-type ovarian cancer patients."

Journal • Oncology • Ovarian Cancer • Solid Tumor • BRCA • GPX4

MDM2 antagonists promote CRISPR/Cas9-mediated precise genome editing in sheep primary cells. (PubMed, Mol Ther Nucleic Acids) - "Besides, we identified three potent small molecules, RITA, Nutlin3, and CTX1, inhibitors of p53-MDM2 interaction, that caused activation of the p53 pathway, resulting in distinct G2/M cell-cycle arrest in response to DNA damage and improved CRISPR-Cas9-mediated HDR efficiency by 1.43- to 4.28-fold in SFFs. Furthermore, we demonstrated that genetic knockout of p53 could inhibit HDR in SFFs by suppressing the expression of several key factors involved in the HDR pathway, such as BRCA1 and RAD51. Overall, this study offers an optimized strategy for the usage of dsDNA repair template, more importantly, the application of MDM2 antagonists provides a simple and efficient strategy to promote CRISPR/Cas9-mediated precise genome editing in sheep primary cells."

Journal • BRCA1 • RAD51

Strategies for Alleviating Tyrosine Kinase Resistance in Acute Myeloid Leukemia By Modulating p53 Signaling Pathway with Small Molecules (ASH 2022) - "While midostaurin and gilteritinib are FDA-approved for these high-risk patients, they only result in a temporary response without transplantation, suggesting the importance of identifying the acquired resistance...Subsequently, cell cytotoxicity assay showed these two cabozantinib-resistant cells were also resistant to quizartinib, sorafenib and gilteritinib... These findings suggested that reactivation of p53 is a potential therapeutic option to alleviate drug resistance in FLT3-mutated AML, provided that AML patients are tested for p53 dysfunction, including TP53 mutational status and downregulation."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • BBC3 • CDKN1A • FLT3 • ZMAT3

Decreased DNA damage and improved p53 specificity of RITA analogs. (PubMed, Mol Cancer Ther) - "We found that RITA analog NSC782846, but not NSC777196, induced p53-regulated genes, targeted oncogene addiction and killed cancer cells upon p53 reactivation, but without induction of DNA damage and inhibition RNA pol II. Our results might demonstrate a method for designing more specific and potent RITA analogs to accelerate translation of p53 targeting compounds from lab bench to clinic."

Journal • CNS Disorders • Oncology • Psychiatry

Novel Allosteric Mechanism of Dual p53/MDM2 and p53/MDM4 Inhibition by a Small Molecule. (PubMed, Front Mol Biosci) - "Ion mobility-mass spectrometry revealed that the binding of RITA to serine 33 and serine 37 is responsible for inducing the allosteric shift in p53, which shields the MDM2 binding residues of p53 and prevents its interactions with MDM2 and MDM4. Our results point to an alternative mechanism of blocking p53 interaction with MDM2 and MDM4 and may pave the way for the development of novel allosteric inhibitors of p53/MDM2 and p53/MDM4 interactions."

Journal • Oncology • MDM4

Reactivation of p53 by RITA Induces Apoptosis in Human Oral Squamous Cell Carcinoma Cells. (PubMed, Anticancer Res) - "The inhibitory effect of RITA on human OSCC cell proliferation is mediated by apoptosis induction through p53 and Bax."

Journal • Head and Neck Cancer • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ANXA5 • BAX • CA9 • MDM2

Restoring p53 Function in Head and Neck Squamous Cell Carcinoma to Improve Treatments. (PubMed, Front Oncol) - "First, compounds targeting degradation or direct inhibition of WT p53, such as PM2, RITA, nutlin-3 and CH1iB, achieve p53 reactivation by affecting p53 inhibitors such as MDM2 and MDMX/4 or by preventing the breakdown of p53 by inhibiting the proteasomal complex. Second, compounds that directly affect mutated p53 by binding it and restoring the WT conformation and transcriptional activity (PRIMA-1, APR-246, COTI-2, CP-31398). Third, treatments that specifically affect HPV cancer cells by targeting the viral enzymes E6/E7 which are responsible for the breakdown of p53 such as Ad-E6/E7-As and bortezomib. In this review, we describe and discuss p53 regulation and its targeting in combination with existing therapies for HNSCC through a new classification of such cancers based on p53 mutation status and HPV infection."

Journal • Review • Head and Neck Cancer • Infectious Disease • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MDM2

PPM1D Is a Therapeutic Target in Childhood Neural Tumors. (PubMed, Cancers (Basel)) - "Comparison of different inhibitors of WIP1 showed that SL-176 was the most potent compound inhibiting medulloblastoma and neuroblastoma growth and had similar or more potent effects on cell survival than the MDM2 inhibitor Nutlin-3 or the p53 activator RITA. SL-176 monotherapy significantly suppressed the growth of established medulloblastoma and neuroblastoma xenografts in nude mice. These results suggest that the development of clinically applicable compounds inhibiting the activity of WIP1 is of importance since PPM1D activating mutations, genetic gain or amplifications and/or overexpression of WIP1 are frequently detected in several different cancers."

Clinical • Journal • Brain Cancer • Medulloblastoma • Neuroblastoma • Oncology • Solid Tumor • MDM2 • PPM1D

Effect of RITA on TP53 Mutant Human Mantle Cell Lymphoma Cell Line and Its Mechanism (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi) - "RITA can inhibit the proliferation and induce the apoptosis of Mino cells significantly. The mechanism may be dependent on the Caspase pathway, but independent on the P53 pathway."

IO biomarker • Journal • Preclinical • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • BCL2 • CASP3 • MDM2 • TP53

Andrographolide Induces Apoptosis in Gastric Cancer Cells through Reactivation of p53 and Inhibition of Mdm-2. (PubMed, Dokl Biochem Biophys) - "Andrographolide inhibited the colony formation abilities in SGC7901 in a p53-dependent manner followed by induction of mitochondrial intrinsic apoptosis through activation of caspases-9 and -3, cleavage of PARP, and inhibition of pro-apoptotic Bcl-2. Andrographolide induced p53 mediated apoptosis in gastric carcinoma cells which adds to a novel approach in anticancer therapies."

IO biomarker • Journal • Gastric Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • BCL2 • CASP9 • MDM2

Real-Time Spatial and Temporal Analysis of the Translocation of the Apoptosis-Inducing Factor in Cells. (PubMed, ACS Chem Biol) - "On the other hand, treatment with apoptosis inducers, such as paclitaxel, silibinin, doxorubicin, actinomycin D, and camptothecin caused AIF translocation to the nucleus after 4 h incubation through AIF binding to CypA, reaching saturation after 6-7 h. It was also found that Hsp70 and CypA regulate AIF translocation in a mutually exclusive manner because they do not interact with AIF simultaneously in cells undergoing apoptosis. The results demonstrate clearly that ANAP-incorporated proteins are powerful to obtain a more in-depth understanding of protein translocation."

Journal • Immunology • Oncology

Editor's Note: Dual Targeting of Wild-Type and Mutant p53 by Small-molecule RITA Results in the Inhibition of N-Myc and Key Survival Oncogenes and Kills Neuroblastoma Cells In Vivo and In Vitro. (PubMed, Clin Cancer Res) - No abstract available

Journal • Preclinical • Neuroblastoma • Oncology • Solid Tumor • MYCN • TP53

Recombinant human bone morphogenetic protein 2 and 7 inhibit the degeneration of intervertebral discs by blocking the Puma-dependent apoptotic signaling. (PubMed, Int J Biol Sci) - "Importantly, administration of rhBMPs in aged rats could inhibit the occurrence of IDD. Our results provide a link between BMP/Smad signaling and Puma-dependent apoptotic signaling, revealing a new mechanism of how BMPs contribute to IDD pathogenesis and providing evidence that rhBMPs may decrease apoptosis and improve the outcome of IDD."

Journal • Oncology • HDAC1 • SMAD4