World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Review

Volume 12, Number 4, August 2021, pages 85-92

Personalized Medicine in Ovarian Cancer: A Perspective From Mexico

Figure 1. Key features of OC. (a) Associated factors. (b) Treatment options. (c) OC FIGO staging. OC: ovarian cancer.

**Table 1.** OC in Numbers in Mexico and the World According to Globocan 2018
	Worldwide	Mexico
Incidence	295,414	4,759
Mortality	184,799	2,765
Prevalence	762,663	12,942

Table 1. OC in Numbers in Mexico and the World According to Globocan 2018

Worldwide

Mexico

Incidence

295,414

4,759

Mortality

184,799

2,765

Prevalence

762,663

12,942

**Table 2.** Milestones in PM of OC
Year	Landmark	Reference
ADAMTS: A disintegrin and metalloproteinase with thrombospondin motifs; AHT: adjuvant hormone therapy; AKT: protein kinase B; ARID1A: AT-rich interaction domain 1A; CA-125: cancer antigen-125; DNA: deoxyribonucleic acid; EZH2: enhancer of Zeste homolog 2; GWAS: genome-wide association study; HE4: human epididymis protein 4; HGSC: high-grade serous ovarian cancer; miRNA: microribonucleic acid; MOC: mucinous ovarian carcinoma; mTOR: mammalian target of rapamycin; OC: ovarian cancer; OCSI: Ovarian Cancer Symptom Index; OS: overall survival; PARP: poly (ADP-ribose) polymerase; PIK3CA: p110α subunit of phosphatidylinositol 3-kinase; PM: personalized medicine; ROCA: risk of ovarian cancer algorithm; VEGF: vascular endothelial growth factor.
2007	VEGF-targeted therapy showed to be effective in the treatment of OC.	[9]
2007	OC screening calculated the OC risk of an individual by analyzing serial CA-125 values via ROCA and made it possible to choose the right dose of medication.	[10]
2007	The OCSI was created, anticipating being useful for early diagnosis and in this way improving personalized treatments.	[11]
2008	Biomarkers for OC, like HE4, were shown to be over-expressed in epithelial OC. Examining values of 11 markers showed that the combination of HE4 and CA-125 had the highest predictive value of this study.	[12]
2008	Screening OC patients for BRCA mutations allowed a new personalized treatment with a PARP inhibitor (AZD2281 blocks the pathway used by BRCA mutated cells to repair DNA damage).	[13]
2010	Use of bevacizumab as the leading molecular targeted agent for OC. Identification of biomarkers to select patients for bevacizumab treatment became an advance because it was well tolerated.	[14]
2011	DICER1 mutations were found in non-epithelial ovarian tumors. Aberrant miRNA processing resulted from DICER1 could be a specific feature in the development of certain types of non-epithelial OC.	[15]
2010	PIK3CA mutations could predict response to PI3K/AKT/mTOR inhibitors. PIK3CA mutations are known to be common in 12% of OC.	[16]
2010	Introduction of neoadjuvant chemotherapy in OC: right therapy to the right person.	[17]
2015	The first genetic map of how HGSC evolves in response to chemotherapy was created. At least four molecular events were associated with acquired resistance.	[18]
2015	ADAMTS mutations were found as a possible predictor of chemosensitivity in OC without BRCA1 or BRCA2 mutations.	[19]
2015	A GWAS for MOC identified three risk associations at 2q13, 2q31.1 and 19q13.2.	[20]
2015	The relation between EZH2 and ARID1A is a potentially effective treatment target for ovarian clear cell carcinoma, where < 50% of ARID1A is mutated and shows a low response to platinum-based chemotherapy.	[21]
2015	BRCAs mutations were detected in 28% of samples of OC cases.	[22]
2016	AHT after surgery becomes a personalized medicine approach for helping extend the OS of the patients with OC.	[23]
2016	Development of a cancer therapy program using integrative genomic data. Therapeutic recommendations were made after considering the genetic and genomic alterations profiles.	[24]
2016	Four commercial tools were compared to identify therapeutic recommendations for a given genetic mutation in cancers.	[25]
2018	A total of 180 BRCAs genetic variants in sporadic OC tumors were found from Mexican patients.	[26]

Table 2. Milestones in PM of OC

Year

Landmark

Reference

ADAMTS: A disintegrin and metalloproteinase with thrombospondin motifs; AHT: adjuvant hormone therapy; AKT: protein kinase B; ARID1A: AT-rich interaction domain 1A; CA-125: cancer antigen-125; DNA: deoxyribonucleic acid; EZH2: enhancer of Zeste homolog 2; GWAS: genome-wide association study; HE4: human epididymis protein 4; HGSC: high-grade serous ovarian cancer; miRNA: microribonucleic acid; MOC: mucinous ovarian carcinoma; mTOR: mammalian target of rapamycin; OC: ovarian cancer; OCSI: Ovarian Cancer Symptom Index; OS: overall survival; PARP: poly (ADP-ribose) polymerase; PIK3CA: p110α subunit of phosphatidylinositol 3-kinase; PM: personalized medicine; ROCA: risk of ovarian cancer algorithm; VEGF: vascular endothelial growth factor.

2007

VEGF-targeted therapy showed to be effective in the treatment of OC.

[9]

2007

OC screening calculated the OC risk of an individual by analyzing serial CA-125 values via ROCA and made it possible to choose the right dose of medication.

[10]

2007

The OCSI was created, anticipating being useful for early diagnosis and in this way improving personalized treatments.

[11]

2008

Biomarkers for OC, like HE4, were shown to be over-expressed in epithelial OC. Examining values of 11 markers showed that the combination of HE4 and CA-125 had the highest predictive value of this study.

[12]

2008

Screening OC patients for BRCA mutations allowed a new personalized treatment with a PARP inhibitor (AZD2281 blocks the pathway used by BRCA mutated cells to repair DNA damage).

[13]

2010

Use of bevacizumab as the leading molecular targeted agent for OC. Identification of biomarkers to select patients for bevacizumab treatment became an advance because it was well tolerated.

[14]

2011

DICER1 mutations were found in non-epithelial ovarian tumors. Aberrant miRNA processing resulted from DICER1 could be a specific feature in the development of certain types of non-epithelial OC.

[15]

2010

PIK3CA mutations could predict response to PI3K/AKT/mTOR inhibitors. PIK3CA mutations are known to be common in 12% of OC.

[16]

2010

Introduction of neoadjuvant chemotherapy in OC: right therapy to the right person.

[17]

2015

The first genetic map of how HGSC evolves in response to chemotherapy was created. At least four molecular events were associated with acquired resistance.

[18]

2015

ADAMTS mutations were found as a possible predictor of chemosensitivity in OC without BRCA1 or BRCA2 mutations.

[19]

2015

A GWAS for MOC identified three risk associations at 2q13, 2q31.1 and 19q13.2.

[20]

2015

The relation between EZH2 and ARID1A is a potentially effective treatment target for ovarian clear cell carcinoma, where < 50% of ARID1A is mutated and shows a low response to platinum-based chemotherapy.

[21]

2015

BRCAs mutations were detected in 28% of samples of OC cases.

[22]

2016

AHT after surgery becomes a personalized medicine approach for helping extend the OS of the patients with OC.

[23]

2016

Development of a cancer therapy program using integrative genomic data. Therapeutic recommendations were made after considering the genetic and genomic alterations profiles.

[24]

2016

Four commercial tools were compared to identify therapeutic recommendations for a given genetic mutation in cancers.

[25]

2018

A total of 180 BRCAs genetic variants in sporadic OC tumors were found from Mexican patients.

[26]

**Table 3.** Current Clinical Studies for OC in Mexico [30]
Title of the study	Recruitment countries	Research sites in Mexico	Duration	Subjects (worldwide/national)
OC: ovarian cancer.
Phase III, open-label, randomized, controlled, multi-center study to assess the efficacy and safety of Olaparib monotherapy versus physician’s choice single-agent chemotherapy in the treatment of platinum-sensitive relapsed ovarian cancer in patients carrying germline BRCA 1/2 mutations.	Argentina, Belgium, Brazil, Canada, Czechia, Hungary, Israel, Italy, Republic of Korea, Mexico, Poland, Spain, and the United States of America	Oaxaca Site Management Organization, S.C., Oaxaca, Oaxaca	6 years	411/64
Hyperthermic intraperitoneal chemotherapy in ovarian carcinoma clinical-stage IIIC and IV during interval laparotomy. Phase II study.	Mexico	National Institute of Cancerology of Mexico	3 years	100/100
Validation of HISPANEL in Mexican patients with a high risk of hereditary breast and ovarian cancer syndrome.	Mexico	National Institute of Cancerology and Tec-Salud-Tecnologico de Monterrey	4 years	1,290/700
Phase 3 randomized placebo-controlled double-blind study of Romiplostim for the treatment of Chemotherapy-induced Thrombocytopenia in patients receiving chemotherapy for treatment of non-small cell lung cancer (NSCLC), ovarian cancer, or breast cancer.	United States of America, Argentina, Austria, Brazil, Bulgaria, Chile, Colombia, Greece, Hungary, Mexico, Peru, Poland, Portugal, Romania, Russian Federation, Spain, Turkey, and Ukraine	Oaxaca Site Management Organization, S.C., Oaxaca, Oaxaca and not specified research sites in San Luis Potosi, San Luis Potosi and La Paz, Baja California Sur	1 year	162/10

Table 3. Current Clinical Studies for OC in Mexico [30]

Title of the study

Recruitment countries

Research sites in Mexico

Duration

Subjects (worldwide/national)

OC: ovarian cancer.

Phase III, open-label, randomized, controlled, multi-center study to assess the efficacy and safety of Olaparib monotherapy versus physician’s choice single-agent chemotherapy in the treatment of platinum-sensitive relapsed ovarian cancer in patients carrying germline BRCA 1/2 mutations.

Argentina, Belgium, Brazil, Canada, Czechia, Hungary, Israel, Italy, Republic of Korea, Mexico, Poland, Spain, and the United States of America

Oaxaca Site Management Organization, S.C., Oaxaca, Oaxaca

6 years

411/64

Hyperthermic intraperitoneal chemotherapy in ovarian carcinoma clinical-stage IIIC and IV during interval laparotomy. Phase II study.

Mexico

National Institute of Cancerology of Mexico

3 years

100/100

Validation of HISPANEL in Mexican patients with a high risk of hereditary breast and ovarian cancer syndrome.

Mexico

National Institute of Cancerology and Tec-Salud-Tecnologico de Monterrey

4 years

1,290/700

Phase 3 randomized placebo-controlled double-blind study of Romiplostim for the treatment of Chemotherapy-induced Thrombocytopenia in patients receiving chemotherapy for treatment of non-small cell lung cancer (NSCLC), ovarian cancer, or breast cancer.

United States of America, Argentina, Austria, Brazil, Bulgaria, Chile, Colombia, Greece, Hungary, Mexico, Peru, Poland, Portugal, Romania, Russian Federation, Spain, Turkey, and Ukraine

Oaxaca Site Management Organization, S.C., Oaxaca, Oaxaca and not specified research sites in San Luis Potosi, San Luis Potosi and La Paz, Baja California Sur

1 year

162/10

**Table 4.** FDA-Approved Drugs for the Treatment of OC [38]
Drug	Manufactures	Administration	Dose	Approval	Mexico
FDA: Food and Drug Administration; OC: ovarian cancer.
Tepadina (thiotepa)	Adienne SA	Injection	15 mg/vial	1959	No
Platinol (cisplatin)	Hq Spclt Pharma	Injection	75 mg/m²	1978	Yes
Doxil (doxorubicin hydrochloride liposome)	Baxter healthcare Corp.	Injection	2 mg/mL	1995	Yes
Gemzar (gemcitabine hydrochloride)	Lilly	Injection	200 mg base/vial	1996	Yes
Taxol (paclitaxel)	Bristol-Myers Squibb	Injection	175 mg/m²	1998	Yes
Hycamtin (topotecan hydrochloride)	SmithKline Beecham Pharmaceuticals	Injection	1.5 mg/m²	1998	Yes
Alkeran (melphalan)	Glaxo Wellcome, Inc.	Tablets	0.2 mg/kg	2001	Yes
Paraplatin (carboplatin aqueous solution)	Bristol-Myers Squibb	Injection	Determined by doctor	2003	Yes
Doxorubicin hydrochloride	Sun Pharm	Injection	50 mg/m²	2013	Yes
Lynparza (Olaparib)	AstraZeneca	Capsules, tablets	300 mg	2014, 2017	Yes
Rubraca (Rucaparib)	Clovis Oncology, Inc.	Tablets	600 mg	2016	No
Zejula (Niraparib)	Tesaro, Inc.	Capsules	300 mg	2017	No
Avastin (bevacizumab)	Genetech, Inc.	Injection	25 mg/mL	2018	Yes

Table 4. FDA-Approved Drugs for the Treatment of OC [38]

Drug

Manufactures

Administration

Dose

Approval

Mexico

FDA: Food and Drug Administration; OC: ovarian cancer.

Tepadina (thiotepa)

Adienne SA

Injection

15 mg/vial

1959

Platinol (cisplatin)

Hq Spclt Pharma

Injection

75 mg/m²

1978

Yes

Doxil (doxorubicin hydrochloride liposome)

Baxter healthcare Corp.

Injection

2 mg/mL

1995

Yes

Gemzar (gemcitabine hydrochloride)

Lilly

Injection

200 mg base/vial

1996

Yes

Taxol (paclitaxel)

Bristol-Myers Squibb

Injection

175 mg/m²

1998

Yes

Hycamtin (topotecan hydrochloride)

SmithKline Beecham Pharmaceuticals

Injection

1.5 mg/m²

1998

Yes

Alkeran (melphalan)

Glaxo Wellcome, Inc.

Tablets

0.2 mg/kg

2001

Yes

Paraplatin (carboplatin aqueous solution)

Bristol-Myers Squibb

Injection

Determined by doctor

2003

Yes

Doxorubicin hydrochloride

Sun Pharm

Injection

50 mg/m²

2013

Yes

Lynparza (Olaparib)

AstraZeneca

Capsules, tablets

300 mg

2014, 2017

Yes

Rubraca (Rucaparib)

Clovis Oncology, Inc.

Tablets

600 mg

2016

Zejula (Niraparib)

Tesaro, Inc.

Capsules

300 mg

2017

Avastin (bevacizumab)

Genetech, Inc.

Injection

25 mg/mL

2018

Yes