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B-cell lymphoma 2 (BCL-2) family proteins primarily work as a programmed cell death regulator, whereby multiple interactions between them determine cell survival. This explains the two major classes of BCL-2 proteins which are anti-apoptotic and pro-apoptotic proteins. The anti-apoptotic proteins are attractive targets for BCL-2 family inhibitors, which result in the augmentation of the intrinsic apoptotic pathway. BCL-2 family inhibitors have been studied extensively for novel targeted therapies in various cancer types, fibrotic diseases, aging-related as well as autoimmune diseases. Navitoclax is one of them and it has been discovered to have a high affinity toward BCL-2 anti-apoptotic proteins, including BCL-2, BCL-W and B-cell lymphoma-extra-large. Navitoclax has been demonstrated as a single agent or in combination with other drugs to successfully ameliorate tumor progression and fibrosis development. To date, navitoclax has entered phase I and phase II clinical studies. Navitoclax alone potently treats small cell lung cancer and acute lymphocytic leukemia, whilst in combination therapy for solid tumors, it enhances the therapeutic effect of other chemotherapeutic agents. A low platelet count has always associated with single navitoclax treatments, though this effect is tolerable. Moreover, the efficacy of navitoclax is determined by the expression of several BCL-2 family members. Here, we elucidate the complex mechanisms of navitoclax as a pro-apoptotic agent, and review the early and current clinical studies of navitoclax alone as well as with other drugs. Additionally, some suggestions on the development of navitoclax clinical studies are presented in the future prospects section.

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The characteristics and functional properties of polysaccharides extracted from Malaysia's seaweeds have not been fully established to date. Hence, this study was carried out to produce high yield fermentable sugars from Kappaphycus alvarezii for the potential production of biotechnology products such as bioflavours. In order to achieve this objective, the effectiveness of hydrolysis process was studied by using chemical treatments, followed by enzymatic treatments. K. alvarezii were hydrolysed in different heating times and temperatures followed by different types of acids and their concentrations. The optimal conditions for chemical hydrolysis were achieved at 8.0 g/100 mL of dried powder K. alvarezii in 0.2 M H2SO4 and HCl at 110 °C for 90 min which produced 34.275 ± 0.976 g/L and 35.872 ± 3.610 g/L, respectively with 42.8% and 44.8% of yield of sugar production. However, there are no significant different between H2SO4 and HCl. Thus, H2SO4 was chose as a catalyst for chemical hydrolysis. As for the combination of chemical and enzymatic hydrolysis, several pH of hydrolysates and incubation temperature were studied. The optimum condition for Celluclast activity was at pH 5.5 and 50 °C incubation temperature which produced the highest reducing sugars with an increment of 15.60 g/L from the chemical hydrolysis alone. The yield of reducing sugars after combining both methods reached 62.35% (49.92 ± 1.163 g/L reducing sugar). From this study, the characterization of these seaweeds can lead to a better understanding of their functional characteristics and promote the exploitation of these natural resources for the production of expensive new biotechnology products.

Combination therapy emerges as a fundamental scheme in cancer. Many targeted therapeutic agents are developed to be used with chemotherapy or radiation therapy to enhance drug efficacy and reduce toxicity effects. ABT-263, known as navitoclax, mimics the BH3-only proteins of the BCL-2 family and has a high affinity towards pro-survival BCL-2 family proteins (i.e., BCL-XL, BCL-2, BCL-W) to induce cell apoptosis effectively. A single navitoclax action potently ameliorates several tumor progressions, including blood and bone marrow cancer, as well as small cell lung carcinoma. Not only that, but navitoclax alone also therapeutically affects fibrotic disease. Nevertheless, outcomes from the clinical trial of a single navitoclax agent in patients with advanced and relapsed small cell lung cancer demonstrated a limited anti-cancer activity. This brings accumulating evidence of navitoclax to be used concomitantly with other chemotherapeutic agents in several solid and non-solid tumors that are therapeutically benefiting from navitoclax treatment in preclinical studies. Initially, we justify the anti-cancer role of navitoclax in combination therapy. Then, we evaluate the current evidence of navitoclax in combination with the chemotherapeutic agents comprehensively to indicate the primary regulator of this combination strategy in order to produce a therapeutic effect.