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Diversity Analysis of Indian Mangrove Organisms to Explore Their Potential in Novel and Value-Added Biomolecules
Published in Jayanta Kumar Patra, Gitishree Das, Sanjeet Kumar, Hrudayanath Thatoi, Ethnopharmacology and Biodiversity of Medicinal Plants, 2019
Angana Sarkar, Sushant Prajapati, Amulya Sai Bakshi, Asma Khatoon, Raghavarapu Swathi, Siddharth Kumar, Arpita Behera, Rahul Pradhan
Mangrove organisms such as sponge have many useful compounds such as cytarabine (Ara C), Vidarabine (Ara-A), Eribulin Mesylate (E7389) which are all FDA approved and targets dangerous diseases such as cancer (Mayer et al., 2016; Newman and Cragg, 2016) (Table 2.3). Other mangrove organisms such as Tunicate, Mollusca, Nudibranch also targets the disease, cancer. The omega 3 fatty acid ethyl esters from fish can be used for the treatment of Hypertriglyceridemia. Some important compounds such as Brentuximab Vedotin (SGN-35) Elisidesin, Glembatumumab Vedotin (CDX 011), SGN-75, ASG-5ME can be obtained from Mollusca majorly found in Baratang and Krishna Godavari mangroves. The bacterium Bryozoa gives Bryostatin, which can treat cancer and Alzheimer’s disease. The soft Coral produces pseudopterosins whose molecular target is Eicosanoid Metabolism and helps in wound healing. The compound Trabectedin (ET 743), which belongs to the alkaloid class targets the minor, grooves of DNA and helps in the treatment of cancer. The compound, Eribulin Mesylate (E7389) obtained from the sponge targets the microtubules for the treatment of cancer. Zincoside, obtained from cone nail is used as an analgesic drug. The compound DMXBA (GTS-21) obtained from worm targets the alpha-7 Nicotinic Acetylcholine Receptor and helps in the treatment of cognition schizophrenia (Table 2.3). Mangrove pharmaceuticals can be used as cytostatic drugs, antiviral drugs, analgetic drugs, antihyperlipidemic drugs and can also be used as diagnostic and experimental tools. The cosmetics industry is also stepping towards the sea, so as to find new ingredients (Fenical et al., 2009; Martins et al., 2014).
Current and emerging biologic therapies for triple negative breast cancer
Published in Expert Opinion on Biological Therapy, 2022
Saba S. Shaikh, Leisha A. Emens
Glembatumumab vedotin is an ADC that targets the glycoprotein NMB (expressed by about 40% of TNBCs) and delivers MMAE. EMERGE was a randomized Phase 2 study that enrolled 125 patients with advanced treatment refractory breast cancer at a 2:1 ratio to receive the ADC, or chemotherapy of investigator’s choice [47]. The primary endpoint, ORR, was 12% in each arm. However, exploratory analyses of TNBC patients showed an ORR of 18% versus 0% with the ADC as compared to chemotherapy. The ORR increased to 40% versus 0% in gpNMB-expressing patients treated with the ADC or chemotherapy, respectively. The Phase 2b METRIC trial enrolled 327 patients with gpNMB-positive metastatic TNBC at a 2:1 ratio to receive either the ADC or capecitabine [48]. There was no significant difference in the primary endpoint of PFS between the arms, at 2.9 versus 2.9 months (HR 0.95, p = 0.76). Clinical development of this agent has been discontinued.
Antibodies to watch in 2018
Published in mAbs, 2018
Hélène Kaplon, Janice M. Reichert
Glembatumumab vedotin (CDX-011, CR011-vcMMAE) is an IgG2 human antibody targeting transmembrane glycoprotein non-metastatic gene B (gpNMB) conjugated to monomethyl auristatin E, a cytotoxic drug that, when released in cancer cells, may lead to tumor cell death. High expression of gpNMB has been reported in TNBC and in basal-like breast cancer (BLBC) and correlates with a poor prognosis and increased risk for recurrence. This mAb is currently being investigated in a pivotal Phase 2 METRIC study (NCT01997333) for patients with metastatic breast cancer whose tumor overexpress gpNMB. Overexpression of gpNMB is defined as greater than or equal to 25% of tumor cells testing positive for gpNMB. Patients are randomized (2:1) into 2 arms: glembatumumab vedotin by IV infusion on day 1 of each 21 day cycle or capecitabine on day 1 through 14 of each 21 day cycle. The primary endpoint is PFS. The study enrolled 327 patients. Celldex Therapeutics has announced that topline results for the primary outcome measure should be available in the second quarter of 2018. Glembatumumab vedotin was granted Fast Track designation for advanced, refractory/resistant gpNMB-expressing breast cancer. The mAb is also in development for the treatment of melanoma.
Pharmacotherapeutic options for patients with refractory breast cancer
Published in Expert Opinion on Pharmacotherapy, 2019
Palma Fedele, Mariangela Ciccarese, Giammarco Surico, Saverio Cinieri
breast cancer is not an immunogenic tumor. Recent efforts reported that basal TNBC may be the most regulated by intratumoral T cells and thus it is reasonable to investigate therapies that target programmed death-1/programmed death ligand-1 (PD1-/PD-L1) in TNBC [77–79]. PD-1 is a checkpoint receptor expressed primarily by activated T cells, and it limits T-cell effector functions. PDL-1 a T cell inhibitory molecule is expressed on cancer cells, tumor-infiltrating inflammatory cells and immune cells. The binding of PD-L1 to PD-1 on T-cells is a major mechanism of tumor immune evasion. Higher expression of PD-L1 in TNBC than in hormone receptor-positive BC was reported [80]. Twenty-six percent of primary TNBCs expressed PD-L1 on the surface of the cancer cells, although the role of PD-L1 as a biomarker is unclear [81]. Based on the current clinical studies, it may not be completely predictive of treatment response. Additionally, there is a variability in the methodologies to assess PD-L1 expression, in the different numerical cut off values for positivity and in the analysis being performed on different types of tissue which include archive, fresh, primary and metastatic specimens. In particular, the phase III randomized trial Keynote 119 is investigating PFS and overall survival of pretreated patients with metastatic TNBC randomly assigned to receive either single agent pembrolizumab or single-agent chemotherapy chosen by the treating physician [82]. Moreover, different immunotherapeutic agents are in clinical development in pretreated TNBC patients. Glembatumumab Vedotin, an antibody–drug conjugate also known as CDX-011, is effective in treating patients who have advanced TNBC and whose tumor cells make a protein called glycoprotein NMB (gpNMB), which glembatumumab vedotin binds to. The METRIC study is a phase IIb study designed to further characterize the safety of CDX-011 treatment in this patient population [83].