Novel Therapeutic Strategies for Refractory Ovarian Cancers: Clear Cell and Mucinous Carcinomas
Abstract
:Simple Summary
Abstract
1. Introduction
2. Clear Cell Carcinoma
2.1. Biological Characteristics
2.2. Previous Clinical Studies for Clear Cell Carcinoma
2.3. Ongoing or Planned Clinical Studies for Clear Cell Carcinoma
2.4. New Pharmacotherapy for Clear Cell Carcinoma
3. Mucinous Carcinoma
3.1. Biological Characteristics
3.2. Chemotherapy for Mucinous Carcinoma
3.3. Clinical Studies Using L-OHP and 5-FU for Mucinous Carcinoma
3.4. New Pharmacotherapy for Mucinous Carcinoma
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Gene | Pathways Affected | Type of Expression Abnormality | Frequency (%) |
---|---|---|---|
ARID1A [18] | SWI/SNF | Mutation | 62 |
ARID1B [18] | SWI/SNF | Mutation | 10 |
PIK3CA [18,19] | PI3K | Mutation | 35–51 |
PTEN [18,19] | PI3K | Mutation | 2–5 |
PIK3R1 [18,19] | PI3K | Mutation | 7–8 |
PIK3R2 [19] | PI3K | Mutation | 5 |
KRAS [19] | MAPK | Mutation | 9 |
ERBB2 [19] | MAPK | Mutation and amplification | 11 |
HNF-1β [20] | Metabolic pathway | Methylation | >80 |
Trials | Patients | N | Arms/Treatments | ORR | Median PFS/ 2-Year Disease-Free Survival Rate *** | Median OS/ 2-Year Survival Rate *** |
---|---|---|---|---|---|---|
JGOG3014 [22] | Stage I-IV First-line | 99 | TC* × 6 CPT-P × 6 | 40 25 | NA NA | NA NA |
JGOG3017 [23] | Stage I-IV First-line | 667 | TC** × 6 CPT-P × 6 | 46.7 29.4 | 77.6% *** 73.0% *** | 87.4% *** 85.5% *** |
GOG268 [24] | StageIII/IV First-line | 45 (Japan) 45 (US/Korea) | TC** + Temsirolimus 25 mg/body × 6 →Temsirolimus 25 mg/body | 71 (Japan) 54 (US/Korea) | 12 (Japan) 11 (US/Korea) | 26 (Japan) 23 (US/Korea) |
GOG254 [25] | Recurrent | 35 | Sunitinib 50 mg/day | 6.7 | 2.7 | 12.8 |
NRG-GY001 [26] | Recurrent | 13 | Cabozantinib 60 mg/day | 0 | 3.6 | 8.1 |
Table. | Patients | Phase | N | Arms/Treatments |
---|---|---|---|---|
GOG283 [31] | Recurrent | II | 35 | Dasatinib 140 mg/day |
NiCCC (ENGOT-GYN1) [32] | Recurrent | II (Randomized) | 120 | SoC Nintedanib 400 mg/day |
NRG-GY-014 [33] | Recurrent | II (basket) | 86 | Tazemetostat |
NRG-GY-016 [34] | Recurrent | II | 14 | Pembrolizumab + Epacadostat |
ATARI [35] | Recurrent | II | 40<, <116 | Ceralasertib 160 mg +/− Olaparib 600mg/day * |
Primary Ovarian Mucinous Carcinomas | Primary Colorectal Mucinous Carcinomas | |
---|---|---|
KRAS mutations | 32–56% [50,51,52,53] | 23–38% [55,56,57] |
HER2 amplification | 18% [54] | <1% [58] |
BRAF mutations | 0% [53] | 14–28% [56,57,59] |
TP53 mutation | 26% [50] | 20–48% [59,60] |
. | Primary Ovarian Mucinous Carcinomas | Primary Colorectal Mucinous Carcinomas |
---|---|---|
CK7 | 79–100% [63,64,65] | 10% [69] |
CK20 | 56–98% [64.65] | 100% [64] |
CDX2 | 18–42% [63,66] | 59% [70] |
MUC2 | 100% [67] | 86–96% [67,71,72,73] |
MUC5AC | 50–100% [64,68] | 2–33% [70,73] |
Author | Patients | N | Regimen | OOR (%) | Median PFS | Median OS |
---|---|---|---|---|---|---|
Shimada M [48] | Stage I-IV | 24 | Platinum based regimen | 12.5 | NA | NA |
Hess V [74] | Stage III/IV | 19 | Platinum based regimen | 26.3 | 5.7 | 12.0 |
Bamias A [75] | Stage III/IV | 24 | Paclitaxel/platinum | 45.0 | NA | 15.4 |
Pectasides D [76] | Stage III/IV | 47 | Platinum based regimen | 38.5 | 11.8 (TTP) | 33.2 |
Pisano C [77] | Stage I-IV | 19 | Platinum based regimen | 42.1 | NA | NA |
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Shoji, T.; Tatsuki, S.; Abe, M.; Tomabechi, H.; Takatori, E.; Kaido, Y.; Nagasawa, T.; Kagabu, M.; Baba, T.; Itamochi, H. Novel Therapeutic Strategies for Refractory Ovarian Cancers: Clear Cell and Mucinous Carcinomas. Cancers 2021, 13, 6120. https://doi.org/10.3390/cancers13236120
Shoji T, Tatsuki S, Abe M, Tomabechi H, Takatori E, Kaido Y, Nagasawa T, Kagabu M, Baba T, Itamochi H. Novel Therapeutic Strategies for Refractory Ovarian Cancers: Clear Cell and Mucinous Carcinomas. Cancers. 2021; 13(23):6120. https://doi.org/10.3390/cancers13236120
Chicago/Turabian StyleShoji, Tadahiro, Shunsuke Tatsuki, Marina Abe, Hidetoshi Tomabechi, Eriko Takatori, Yoshitaka Kaido, Takayuki Nagasawa, Masahiro Kagabu, Tsukasa Baba, and Hiroaki Itamochi. 2021. "Novel Therapeutic Strategies for Refractory Ovarian Cancers: Clear Cell and Mucinous Carcinomas" Cancers 13, no. 23: 6120. https://doi.org/10.3390/cancers13236120