TABLE 6.

Mechanisms of antitumor drug resistance mediated by CAAs.

Tumor type	Drug resistance	Mechanisms	References
ALL	ASNase	CAAs producing both ASN and GLN, counteracting the effects of ASNase.	Ehsanipour et al., 2013
	Vincristine	CAAs secreting SDF-1α, promoting the migration of ALL toward adipose tissue.	Pramanik et al., 2013
	Daunorubicin	CAAs decreasing daunorubicin concentration in ALL cells by expressing daunorubicin-metabolizing enzymes.	Sheng et al., 2017
Breast cancer	Trastuzumab	Adipose-derived factors decreasing the secretion of INF-γ in natural killer cells.	Duong et al., 2015
	Doxorubicin	CAAs inducing the overexpression of MVP in tumor cells, increasing drug efflux and decreasing drug intracellular accumulation.	Lehuédé et al., 2019
CRC	5-FU	CAAs secreting leptin activating the PI3K/AKT signaling pathway.	Bartucci et al., 2010
Myeloma	Bortezomib	CAAs derived leptin promoting the activation of JAK/STAT-PI3K/AKT pathway.	Yu et al., 2016
	Melphalan, bortezomib	CAAs derived adipokines activating JAK/STAT3 signaling and inducing the upregulation of autophagic proteins, promoting autophagy.	Liu Z. et al., 2015
Ovarian cancer	Paclitaxel	CAAs-derived exosomes transferring higher levels of miR21 to the cancer cells.	Yeung et al., 2016
	Cisplatin	CAAs releasing AA, activating the Akt pathway in ovarian cancer cells.	Yang et al., 2019
	Carboplatin	Adipocytes inducing FABP4 expression.	Mukherjee et al., 2020

CAAs, cancer associated adipocytes; ALL, acute lymphoblastic leukemia; ASNase, L-asparaginase; ASN, amino acids asparagine; GLN, glutamine; ADCC, antibody-dependent cellular cytotoxicity; CRC, Colorectal cancer; 5-FU, 5-fluorouracil; miR21, microRNA-21; LDs, lipid droplets; ROS, reactive oxygen species; AA, Arachidonic acid; PDAC, pancreatic ductal adenocarcinoma.