China
Africa
Explore chapters and articles related to this topic
Advances in the Treatment of Brain Metastases
Published in Kishan J. Pandya, Julie R. Brahmer, Manuel Hidalgo, Lung Cancer, 2016
Malika L. Siker, Minesh P. Mehta
Radiosensitizers are designed to increase the efficacy of radiotherapy in tumors with no added damage to normal tissue. Historically, radiosensitizers have demonstrated little value in patients with brain metastases. Misonidazole, bromodeoxyuridine, lonidamine, nimustine, fluorouracil, and others have failed to show significant benefit in randomized trials (114,115). The development of two new compounds, motexafin gadolinium (MGd) and efaproxaril, has renewed interest in this domain.
DQAsomes as Mitochondria-Targeted Nanocarriers for Anti-Cancer Drugs
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Shing-Ming Cheng, Sarathi V. Boddapati, Gerard G. M. D’Souza, Volkmar Weissig
Several conventional anti-cancer drugs, such as doxorubicin, and cisplatin, have no direct effect on mitochondria.51 These conventional chemotherapeutic agents elicit mitochondrial permeabilization in an indirect fashion by induction of endogenous effectors that are involved in the physiologic control of apoptosis.1 However, a variety of clinically approved drugs such as paclitaxel,52–60 VP-16 (etoposide)61–64 and vinorelbine58 as well as an increasing number of experimental anticancer drugs such as betulinic acid, lonidamine, CD-437 (a synthetic retinoids) and ceramide (reviewed in1) have been found to act directly on mitochondria resulting in triggering apoptosis. These agents may induce apoptosis in circumstances in which conventional drugs fail to act because endogenous apoptosis inducing pathways, e.g., such as those involving p53, death receptors or apical caspase activation, are disrupted, leading to the apoptosis-resistance of tumor cells. For example, several in vitro and in vivo studies have shown that the synthetic retinoid CD437 is able to induce apoptosis in human lung, breast, cervical and ovarian carcinoma cells (reviewed in Kaufmann and Gores 2000). It could be demonstrated that in intact cells, CD437-dependent caspase activation is preceded by the release of cytochrome C from mitochondria.65 Moreover, it was shown that when added to isolated mitochondria, CD437 causes membrane permeabilization and that this effect is prevented by inhibitors of the mPTPC such as cyclosporine A. CD437 constitutes an experimental drug that exerts its cytotoxic effect via the mPTPC, i.e., by acting directly at the surface or inside of mitochondria.
Spheroids in Radiobiology Research
Published in Rolf Bjerkvig, Spheroid Culture in Cancer Research, 2017
Spheroids composed of human cervical carcinoma cells (HeLa-S3) have been used in a pair of studies of combined radiation and drug cytotoxicity. He et al.182 studied the effects of AT 1727, a clinical chemotherapeutic agent, alone and in combination with radiation, using regrowth delay as an end point. There was an increased growth delay when comparing the radiation and drug combination to radiation alone, using a dose of drug that had a minimal effect on regrowth when given without radiation. It should be noted that AT1727 was present throughout the regrowth period, and the increased effectiveness of the combination treatment was not shown to be greater than additive. However, treatment with a similar chemotherapeutic analogue (ICRF159) gave no increased regrowth delay when combined with radiation. Using the same spheroid system, Kim et al.183 have recently shown that lonidamine, an inhibitor of energy metabolism, greatly increased spheroid growth delay when given in combination with fractionated doses of radiation. Combined treatment of spheroids with lonidamine and single-dose radiation exposures showed no enhancement of the growth delay, as compared to radiation treatment alone. As above, these effects were determined on spheroids exposed to the drug throughout the entire regrowth period. Removal of the drug during regrowth after fractionated radiation and drug exposure resulted in an immediate increase in the spheroid growth rate. The authors proposed that this drug was not acting by inhibiting the repair of radiation damage, but that fractionated radiation treatment made the cells more sensitive to the growth inhibitory action of lonidamine. No mechanism was proposed to explain the connection between radiation exposure and increased sensitivity to inhibition of energy metabolism.
Targeting glucose metabolism to develop anticancer treatments and therapeutic patents
Published in Expert Opinion on Therapeutic Patents, 2022
Yan Zhou, Yizhen Guo, Kin Yip Tam
Indazole derivatives (1–1) have been investigated for cancer treatment since 1970ʹs [16]. One of the most famous ones, lonidamine (1-1-1), is an approved drug in a few countries in Europe for several types of human cancer treatment. 1-1-1 is capable of inhibiting of mitochondria bounded HK2 and then reducing ATP generation [22]. Mark Matteucci and his team found that 1-1-1 and its analogs (1-1-2, 1-1-3) with high aqueous solubility were useful in treating or preventing cancer, benign prostatic hyperplasia, macular degeneration, and prostatic intraepithelial neoplasia, or for use as an anti-spermatigenic agent with effective doses around 380.00 µM/mL in cells [23]. In addition to that, the effective dose of 1-1-1 was relatively safe for combination therapy [24].
Indazole derivatives and their therapeutic applications: a patent review (2013-2017)
Published in Expert Opinion on Therapeutic Patents, 2018
Ireen Denya, Sarel F. Malan, Jacques Joubert
Indazole derivatives have also made a mark in the line of cancer drugs through molecules that target tumor cell-specific metabolic pathways. Lonidamine (Figure 3) is currently registered for cancer treatment in some countries such as Italy and Australia. It acts by inhibiting the glycolytic enzyme hexokinase II, the electron transport chain, and the mitochondrial permeability transition pore. It has recently become increasingly apparent that the anticancer effects of lonidamine do not occur through a single target, that is, the drug works at multiple sites in a nonspecific manner. Irrespective of the molecular targets, what lonidamine does in the end is to undo what the tumor cells have done in terms of reprogramming cellular metabolism and mitochondrial function [22,23].
Antifungal effects and potential mechanisms of lonidamine in combination with fluconazole against Candida albicans
Published in Expert Review of Anti-infective Therapy, 2021
Xueqi Chen, Yinping Shi, Yiman Li, Shan Su, Peng Wang, Shujuan Sun
Lonidamine (LND) is clinically used as an unconventional anti-tumor agent which can interfere with energy metabolism of cancer cells through inhibiting glycolysis pathway [7,8]. Furthermore, LND has been reported to exert anti-tumor activities by affecting NAD-linked electron transport, inducing cellular reactive oxygen species and inhibiting succinate-ubiquinone reductase activity of mitochondrial complex II [8,9]. Several studies have suggested that the anti-tumor activity will be more effective and the drug resistance will be reversed when LND combines with adriamycin and epirubicin [9–11]. However, there are no reports have illustrated the antifungal activity of LND alone or its combined effects with FLC against C. albicans.