Early-stage + HR+ HER2+ Invasive Breast Carcinoma in Older Women: Current Treatment and Future Perspectives for DeltaRex-G, a Inhibitor.

Women with HR+HER2+ early-stage breast cancer are disadvantaged by the lack of clinical trials focused on women ≥70 years of age. In the past years, there has been increasing controversy on the use of toxic chemotherapy as standard of care treatment for early- stage HR+ HER2+ breast carcinoma in older women. With precision medicine coming of age, molecular profiling of tumors and circulating tumor DNA has identified target oncogenes that could be used in designing an optimal treatment for this group of women.

Phase I-II study using DeltaRex-G, a tumor-targeted retrovector encoding a cyclin G1 inhibitor for metastatic carcinoma of breast.

Metastatic breast cancer is associated with a poor prognosis and therefore, innovative therapies are urgently needed. Here, we report on the results of a Phase I-II study using DeltaRex-G for chemotherapy resistant metastatic carcinoma of breast. Dose limiting toxicity; Antitumor activity.

Three year results of Blessed: Expanded access for DeltaRex-G for an intermediate size population with advanced pancreatic cancer and sarcoma (NCT04091295) and individual patient use of DeltaRex-G for solid malignancies (IND# 19130).

Innovative treatments are urgently needed for metastatic cancer. DeltaRex-G, a tumor-targeted retrovector encoding a dominant-negative/cytocidal cyclin G1 (CCNG1 gene) inhibitor construct-has been tested in over 280 cancer patients worldwide in phase 1, phase 2 studies and compassionate use studies, demonstrating long term (>10 years) survivorship in patients with advanced cancers, including pancreatic cancer, osteosarcoma, malignant peripheral nerve sheath tumor, breast cancer, and B-cell lymphoma. Endpoints: Survival, response, treatment-related adverse events.

Tumor protein p53 mutation in archived tumor samples from a 12-year survivor of stage 4 pancreatic ductal adenocarcinoma may predict long-term survival with DeltaRex-G: A case report and literature review.

DeltaRex-G is a replication-incompetent amphotropic murine leukemia virus-based retroviral vector that displays a collagen-matrix-targeting decapeptide on its surface envelope protein, gp70, and encodes a cytocidal 'dominant negative', i.e. a truncated construct of the executive cyclin G1 () oncogene.

A Phase 1b Dose Escalation Trial of NC-6300 (Nanoparticle Epirubicin) in Patients with Advanced Solid Tumors or Advanced, Metastatic, or Unresectable Soft-tissue Sarcoma.

Purpose: NC-6300 is a novel nanoparticle formulation of epirubicin that has a pH-sensitive linker conjugated to epirubicin. It exhibits selective tumor accumulation owing to enhanced permeability and retention effect. We conducted a phase 1b trial to determine MTD and recommended phase II dose (RP2D) of NC-6300 monotherapy in advanced, metastatic, or unresectable solid tumors, including soft-tissue sarcomas.

Phase 1 study of the MDM2 inhibitor AMG 232 in patients with advanced P53 wild-type solid tumors or multiple myeloma.

Background This open-label, first-in-human, phase 1 study evaluated AMG 232, an oral selective MDM2 inhibitor in patients with TP53 wild-type (P53WT), advanced solid tumors or multiple myeloma (MM). Methods In the dose escalation (n = 39), patients with P53WT refractory solid tumors enrolled to receive once-daily AMG 232 (15, 30, 60, 120, 240, 480, and 960 mg) for seven days every 3 weeks (Q3W). In the dose expansion (n = 68), patients with MDM2-amplified (well-differentiated and de-differentiated liposarcomas [WDLPS and DDLPS], glioblastoma multiforme [GBM], or other solid tumors [OST]), MDM2-overexpressing ER+ breast cancer (BC), or MM received AMG 232 at the maximum tolerated dose (MTD).

A Phase I-II Study Using Rexin-G Tumor-Targeted Retrovector Encoding a Dominant-Negative Cyclin G1 Inhibitor for Advanced Pancreatic Cancer.

Rexin-G is a replication-incompetent retroviral vector displaying a cryptic -binding peptide for targeting abnormal Signature () proteins in tumors and encoding a dominant-negative human cyclin G1 construct. Herein we report on the safety and antitumor activity of escalating doses of Rexin-G in gemcitabine-refractory pancreatic adenocarcinoma, with one 10-year survivor. For the safety analysis (n = 20), treatment-related grade 1 adverse events included fatigue (n = 6), chills (n = 2), and headache (n = 1), with no organ damage and no DLT.

Cell cycle checkpoint control: The cyclin G1/Mdm2/p53 axis emerges as a strategic target for broad-spectrum cancer gene therapy - A review of molecular mechanisms for oncologists.

Basic research in genetics, biochemistry and cell biology has identified the executive enzymes and protein kinase activities that regulate the cell division cycle of all eukaryotic organisms, thereby elucidating the importance of site-specific protein phosphorylation events that govern cell cycle progression. Research in cancer genomics and virology has provided meaningful links to mammalian checkpoint control elements with the characterization of growth-promoting proto-oncogenes encoding c-Myc, Mdm2, cyclins A, D1 and G1, and opposing tumor suppressor proteins, such as p53, pRb, p16 and p21, which are commonly dysregulated in cancer. While progress has been made in identifying numerous enzymes and molecular interactions associated with cell cycle checkpoint control, the marked complexity, particularly the functional redundancy, of these cell cycle control enzymes in mammalian systems, presents a major challenge in discerning an optimal locus for therapeutic intervention in the clinical management of cancer.

Eribulin in advanced liposarcoma and leiomyosarcoma.

The heterogeneity of soft tissue sarcomas (STS) presents a formidable management challenge. Consequently, one of the main research goals is to define specific tailored therapy for each histological subtype and to develop a more personalised approach to treatment. The standard first line chemotherapy for advanced STS is doxorubicin, with or without ifosfamide, however, a number of different drugs are emerging as active therapies beyond first-line.

Rexin-G, a tumor-targeted retrovector for malignant peripheral nerve sheath tumor: A case report.

Soft tissue sarcoma is a rare neoplasm of mesenchymal origin, accounting for only ~1% of all adult cancers and consisting of 75 histological subtypes. In the present report, the unique case of a 14 year-old female with metastatic malignant peripheral nerve sheath tumor (formerly, malignant melanotic schwannoma) of the parotid gland, who experienced a durable response and sustained tumor control with Rexin-G, a tumor-targeted retroviral expression vector encoding an anti-cyclin G1 construct, is described. Post-parotidectomy, and prior to the administration of Rexin-G, the patient received various chemotherapy regimens, including doxorubicin, ifosfamide, temozolomide, sorafenib, and an immunological therapy with interleukin-2, which only resulted in the further progression of lung metastases.

Trabectedin for Soft Tissue Sarcoma: Current Status and Future Perspectives.

Unlabelled: Trabectedin (ET743, Yondelis(®), manufactured by Baxter Oncology GmbH, Halle/Westfalen, Germany, for Janssen Products, LP, Horsham, PA), derived from the marine ascidian, Ecteinascidia turbinata, is a natural alkaloid with multiple complex mechanisms of action. On 23 October 2015, 15 years after the results of the first Phase 1 clinical trial using trabectedin for chemotherapy-resistant solid malignancies was reported, and 8 years after its approval in Europe, the United States Food and Drug Administration (USFDA) finally approved trabectedin for the treatment of unresectable or metastatic liposarcoma or leiomyosarcoma that has failed a prior anthracycline-containing regimen. Approval was based on the results of a pivotal Phase 3 trial involving a 2:1 randomization of 518 patients (who were further stratified by soft tissue sarcoma subtype), in which a significant improvement in progression-free survival was reported in the trabectedin-treated group vs.