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European Journal of Pharmaceutical Sciences 134 (2019) 116–137
was reported to induce autophagy and decrease prostate tumor growth in the bone (Gaur et al., 2015).
Malignant transformation requires initiation and maintenance of fundamental changes in biological processes to support the high levels of energy consumption and to supply the building blocks for tumor mass under stressful conditions. Additionally, uncontrolled prolifera-tion results in tumor growth to a degree that the existing vasculature can no longer support the tumor mass. This triggers cellular adaptations for survival under nutrient- and oxygen-limiting conditions. Therefore, alterations in the expression levels of a set of genes also ensure onco-genic activation and metabolic re-programming to survive during stressful conditions.
mTOR, MYC, and RAS are among the most popular signaling pathways which are frequently hijacked by the cancer Herboxidiene to be exploited for re-programming of all metabolism, protein and organelle turnover, cell survival and bio-energetic functions (Qiu and Simon, 2015). Interestingly, almost all of these cancer-related signaling path-ways are also found to intersect with autophagy at multiple levels. These observations suggest that autophagy plays dynamic and complex roles in cancer, which in fact might explain the two-faced nature of autophagy in carcinogenesis (Kimmelman and White, 2017). Evidence suggests that in the early stages of malignant transformation and/or cancer progression autophagy may act as a tumor suppressor, whereas in later stages it displays a rather protumorigenic nature to promote tumor maintenance and confer resistance to therapies. Although, tar-geting the autophagy-related pathways seems to be a promising tool for developing novel cancer therapeutics, findings point to the fact that the underlying molecular mechanisms and the specific targets of autophagy in cancer must be defined before it can be eﬀectively exploited in pharmaceutical and medical research areas.
To achieve this goal, important questions such as how the autop-hagic activity is diﬀerentially regulated in diﬀerent cancers or which factors determine the tissue-specific inhibition and/or activation of autophagy should be addressed. Additionally, animal models would allow tissue/organ specific, diﬀerential regulation of autophagic ac-tivity may also open new avenues for exploring the molecular con-nections between autophagy and cancer.
Conflict of interest
The authors declare that there are no conflicts of interests.
This work was supported by Scientific and Technological Research Council of Turkey (TUBITAK)-1001 Grant number: 114Z836. YA is supported by TUBITAK-BIDEB 2211 Scholarships for his PhD studies.
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