Autophagy: shaping the tumor microenvironment and therapeutic response

ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death

“…33,34 In view of our recent findings that Hyp-PDT was in fact capable of inducing bona fide ICD 9,17 13,32 it was imperative to ascertain the impact of autophagy on the emission of ecto-CALR and secreted ATP after Hyp-PDT. However, contrary to the chemotherapy-induced ATP secretion, 13 we observed that Hyp-PDT-induced ATP secretion was independent of autophagy.…”

“…13 Moreover, autophagy also plays an important role in optimal ATP release from cancer cells undergoing chemotherapy-induced ICD. 13,32 We have previously observed that Hyp-PDT-mediated phox-ER stress 9,22 in cancer cells causes accumulation of oxidatively damaged proteins (characterized by the presence of protein carbonyls) along with stimulation of the autophagic flux. 33,34 Autophagy contributes to the clearance of these oxidatively damaged proteins, 33 thereby mitigating the damage caused by Hyp-PDT-induced ROS at the ER.…”

Glutaminolysis and autophagy in cancer

“…65 Autophagy is primarily a prosurvival adaptive response that enables cells to tolerate unfavorable conditions, including those to which cancer cells are exposed. 16,55,[66][67][68][69][70] In response to metabolic stress, caused by limited nutrient and oxygen, autophagy is induced resulting in the degradation of some cellular components and their recycling. This provides nutrients and energy necessary to sustain metabolism; in the case of cancer cells, this ensures tumor growth and survival.…”

“…[71][72][73] In contrast, in advanced stages of tumorigenesis, autophagy may contribute to tumor progression by providing nutrients that allow cell survival under stressful conditions (e.g., oncogene activation, changes in metabolism, hypoxia, ROS accumulation, and acidic pH). 66,67,69,74 Thus, RRAS-induced transformation and tumorigenesis requires autophagy to sustain tumor metabolism and growth. 75 Similarly, BRAF V600E -lung driven tumors become addicted to autophagy to sustain mitochondrial glutamine metabolism and tumor growth.…”

HER2/neu: an increasingly important therapeutic target. Part 1: basic biology & therapeutic armamentarium

“…The co-targeting of other biological processes, such as the autophagy pathway, or other signaling pathways, such as the HedgeHog pathway, may be beneficial and could be simultaneously impacted by agents such as the HSP90 inhibitors [321][322][323]. Similarly targeting the microenvironment in which tumors survive may be a complimentary approach [324,325].…”