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Kondapuram et al. J Cancer Metastasis Treat 2019;5:32 I http://dx.doi.org/10.20517/2394-4722.2018.105 Page 21 of 25

reviewed and analyzed the available autophagy inducers/inhibitors. Except for the mTOR targeting rapalogs,
no other autophagy targeting agents are approved in the clinics for cancer treatment. Currently, chloroquine
and hydroxychloroquine are being clinically tested as autophagy modulators either alone or in combination
with other anti-cancer therapeutics (e.g., temozolomide, bortezomib, temsirolimus, vorinostat, doxorubicin,
etc.). Eventhough hydroxychloroquine shows partial response and improves treatment outcomes in various
cancers such as melanoma, colorectal cancer, myeloma and renal cell carcinoma, dose related toxicity may
preclude its widespread use as autophagy modulator. However, this may change soon as several groups
are developing molecules to various drug targets such as ULK and Vps34 within the autophagy signaling
pathway. Developing selective autophagy modulators with minimal cross-talk with other targets will be
challenging and crucial for making autophagy modulation as a successful strategy for cancer therapy.
Moreover, patient selection based on the alteration in the autophagy signaling pathways could pave way for
better treatment outcomes for autophagy modulators.

The importance of autophagy related research can be fathomed from the ever increasing number of
publications (90 articles in the year 2000, 2050 in 2010 and 6700 articles in 2018; scopus data) and the fact
that 2016 Nobel prize in Physiology or Medicine was awarded to Prof. Yoshinori Ohsumi for his research
on Autophagy in yeast. Eventhough, we have made big strides in understanding the autophagy process,
the complete molecular machinery of autophagy, the signaling process involved and their roles in various
disease conditions are not yet completely elucidated in humans. Future research should hold promise as well
as provide insights in these directions for identifying better treatment for cancer and other diseases.

DECLARATIONS
Authors’ contributions
Collected the literature and wrote the article: Kondapuram SK, Sarvagalla S
Collected the literature, corrected the article and approved: Coumar MS

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

REFERENCES
1. Morel E, Mehrpour M, Botti J, Dupont N, Hamaï A, et al. Autophagy: a druggable process. Annu Rev Pharmacol Toxicol 2017;57:375-
98.
2. Saha S, Panigrahi DP, Patil S, Bhutia SK. Autophagy in health and disease: a comprehensive review. Biomed Pharmacother
2018;104:485-95.