Introduction
Drug-metabolizing CYP enzymes
Expression of CYP3A4, CYP3A5, and CYP2C8 in tumors
Study | References | CYP3A | CYP2C | ||||||
---|---|---|---|---|---|---|---|---|---|
Protein | mRNA | Protein | mRNA | ||||||
Tumor (n) | Healthy (n) | Tumor (n) | Healthy (n) | Tumor (n) | Healthy (n) | Tumor (n) | Healthy (n) | ||
Breast cancer | |||||||||
Albin et al. (1993) | [68] | 0% (12) | 0% (12) | – | – | 0% (12) | 0% (12) | – | – |
Hellmold et al. (1998) | [63] | – | 0%(15) | 75% (4) | 73% (15) | – | 0% (14)c | 100% (4) | 100% (15) |
Murray et al. (1993) | [66] | 22% (54)a | – | – | – | – | – | – | – |
Huang et al. (1996) | [62] | – | – | 15% (13) | 73% (11)a 82% (11)b | – | – | 100% (13) | 100% (11) |
Yokose et al. (1999) | [67] | 0% (6) | – | – | – | 33% (6) | – | – | – |
Iscan et al. (2001) | [64] | – | – | 0% (8)a 0% (4)b | 0% (8)a 0% (4)b | – | – | 83% (6) | 83% (6) |
Miyoshi et al. (2002) | [101] | 37% (38)a,d | – | – | – | – | – | – | – |
El-Rayes et al. (2003) | [56] | + (29) | + (29) | – | – | – | – | – | – |
Kapucuoglu et al. (2003) | [29] | 100% (25)a | 68% (25)a | – | – | – | – | – | – |
Knüpfer et al. (2004) | [72] | – | – | – | – | – | 100% (10)c | – | |
Schmidt et al. (2004) | [71] | 100% (11)a 0% (10)b | – | – | – | – | – | – | |
Miyoshi et al. (2005) | [102] | 52% (31)a | – | – | – | – | – | – | – |
Haas et al. (2006) | [70] | 25% (393)a,b | – | – | – | – | – | – | – |
Vaclavikova et al. (2007) | [65] | – | – | BLQ (40)a | BLQ (40)a | – | – | ||
Murray et al. (2010) | [32] | 52% (170)a,d,e 19% (170)b,d,e | – | – | – | 30% (170) | – | – | – |
Sakurai et al. (2011) | [103] | 55% (42)a | – | – | – | – | – | – | – |
Floriano-Sanchez et al. (2014) | [69] | + (48)*,a | + (48)a | – | – | – | – | – | – |
Prostate cancer | |||||||||
Murray et al. (1995) | [79] | 61% (51) | – | – | – | 25% (51) | – | – | – |
Yokose et al. (1999) | [67] | 0% (6) | – | – | – | 83% (6) | – | – | – |
Finnström et al. (2001) | [58] | – | – | 11% (28)a,f 86% (28)b,f | 11% (28)a,f 86% (28)b,f | – | – | – | – |
Koch et al. (2002) | [74] | – | – | – | 0% (47)a + (47)b | – | – | – | – |
Di Paolo et al. (2005) | [80] | – | 58% (24)a 54% (24)b | – | – | – | – | – | – |
Moilanen et al. (2007) | [77] | – | 100% (6)b | – | – | – | – | – | – |
Bièche et al. (2007) | [54] | – | – | – | + (32)b | ||||
Leskelä et al. (2007) | [76] | 0% (35)b | 100% (10)b | 0% (10)b | + (10)b | – | – | – | – |
Fujimura et al. (2009) | [81] | 75% (107)a | 93% (88)a | – | – | – | – | – | – |
Mitsiades et al. (2012) | [75] | – | – | + (146)a,b | + (29)**,a,b | – | – | – | – |
NSCLC | |||||||||
Nakajima et al. (1994) | [85] | – | – | – | – | + (27) | + (11) | – | – |
Kivistö et al. (1995) | [86] | 25% (32) | 34% (32) | – | – | – | – | – | – |
Kivistö et al. (1996) | [87] | 100% (8) | 100% (8) | 0% (8)a 50% (8)b | 0% (8)a 100% (8)b | – | – | – | – |
Anttila et al. (1997) | [88] | – | 18,5% (27)a | – | 13% (8)a 100% (8)b | – | – | – | – |
Macé et al. (1998) | [84] | – | – | – | 0% (14)a 93% (14)b | – | – | – | 100% (14) |
Yokose et al. (1999) | [67] | 0% (18) | 0% (18) | ||||||
Fujitaka et al. (2001) | [90] | – | – | + (10)a | + (10)a | – | – | + (10)* | + (10) |
Bièche et al. (2007) | [54] | – | – | – | + (6)b | – | – | – | – |
Qixing et al. (2017) | [89] | 74% (87)***,a,d + (87)b,d | + (87)a + (87)***,b | – | – | – | – | – | – |
Endometrial cancer | |||||||||
Hukkanen et al. (1998) | [94] | – | – | – | 57% (7)a 43% (7)b | – | – | – | – |
Yokose et al. (1999) | [67] | 0% (12) | 0% (12) | ||||||
Sarkar et al. (2003) | [95] | – | – | – | 57% (23)a | – | – | – | – |
Masuyama et al. (2003) | [50] | – | – | + (20)a | – | – | – | – | – |
Ovarian cancer | |||||||||
Yokose et al. (1999) | [67] | 0% (12) | – | – | – | 0% (12) | – | – | – |
Klose et al. (1999) | [91] | – | – | – | – | – | – | – | 100% (1) |
Downie et al. (2005) | [98] | 91% (99)/ 80% (22)a,g 66% (99)/ 55% (22)b,g | 64% (13)a 55% (13)b | – | – | 17% (99)/ 10% (22)g | 36% (13) | – | – |
Bièche et al. (2007) | [54] | – | – | – | + (15)b | – | – | – | + (15) |
DeLoia et al. (2008) | [97] | – | – | 9% (47)a 89% (47)b | – | – | – | 69% (48)c | – |
Breast cancer
Prostate cancer
Non-small cell lung cancer (NSCLC)
Endometrial cancer
Ovarian cancer
Taxanes and CYP3A expression in tumor cells
Concomitant treatment with taxanes and HIV-protease inhibitors
Cell line | PI | Proposed effect | References |
---|---|---|---|
NCI-H460 NCI-H520 | Nelfinavir | Nelfinavir-induced inhibition of Akt signaling leading to more sensitivity to docetaxel | [114] |
DU145 cell line | Ritonavir | Increased effect of docetaxel on activation of caspase-3 and cleavage of PARP | [99] |
DU145 cell line | Ritonavir | Reduced DNA-binding activity of NFκB, surpassing one resistance mechanism of docetaxel | [99] |
DU145 cell line | Ritonavir | Blocked the docetaxel-induced increase in CYP3A4 mRNA, decreasing the metabolism of docetaxel | [99] |