Sex steroid hormones and DNA repair regulation: Implications on cancer treatment responses

Rangsrikitphoti, Pattarasiri; Marguez-Garban, Diana C; Pietras, Richard J.; McGowan, Eileen; Boonyaratanakornkit, Viroj

doi:10.1016/j.jsbmb.2022.106230

Cited by 3 publications

(4 citation statements)

References 153 publications

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“…Over the years, strategies that modulate these hormones or their receptors have shown promise across various cancers. Tamoxifen, for instance, has become a cornerstone for ER+ breast cancer due to its ability to antagonize estrogen receptors ( 165 ), significantly reducing recurrence rates. Aromatase inhibitors, such as letrozole and anastrozole, by decreasing estrogen production, hinder tumor growth ( 166 ).…”

Section: Clinical Outcomes and Observationsmentioning

confidence: 99%

“…Some studies, like the Women’s Health Initiative, have shown an increased risk of breast cancer with combined estrogen-progestin therapy, while estrogen-only therapy might have a protective effect. Additionally, other studies have highlighted an increased ovarian cancer risk with prolonged HRT ( 165 , 176 ), whereas evidence suggests a protective effect against colorectal cancer ( 37 ). The effects of estrogen and its receptors on the immune tumor microenvironment in breast cancer ( 25 ) further complicate this dynamic.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

“…As biotechnological advancements like antibody-drug conjugates emerge, these allow for a more targeted delivery to hormone-sensitive tumors. The potential of gene therapy in modulating specific hormonal pathways also presents promising avenues for treatment, especially when considering how sex steroid hormones might interact with DNA repair components affecting genotoxic therapy response ( 165 ). Additionally, insights into sex differences in immunotherapy responses ( 33 ) highlight the potential of novel combinations that might be more tailored to the individual’s hormonal landscape.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

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Sex-specific outcomes in cancer therapy: the central role of hormones

Bakhshi,

Ho,

Zanganeh

2024

Front. Med. Technol.

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Sex hormones play a pivotal role in modulating various physiological processes, with emerging evidence underscoring their influence on cancer progression and treatment outcomes. This review delves into the intricate relationship between sex hormones and cancer, elucidating the underlying biological mechanisms and their clinical implications. We explore the multifaceted roles of estrogen, androgens, and progesterone, highlighting their respective influence on specific cancers such as breast, ovarian, endometrial, and prostate. Special attention is given to estrogen receptor-positive (ER+) and estrogen receptor-negative (ER−) tumors, androgen receptor signaling, and the dual role of progesterone in both promoting and inhibiting cancer progression. Clinical observations reveal varied treatment responses contingent upon hormonal levels, with certain therapies like tamoxifen, aromatase inhibitors, and anti-androgens demonstrating notable success. However, disparities in treatment outcomes between males and females in hormone-sensitive cancers necessitate further exploration. Therapeutically, the utilization of hormone replacement therapy (HRT) during cancer treatments presents both potential risks and benefits. The promise of personalized therapies, tailored to an individual’s hormonal profile, offers a novel approach to optimizing therapeutic outcomes. Concurrently, the burgeoning exploration of new drugs and interventions targeting hormonal pathways heralds a future of more effective and precise treatments for hormone-sensitive cancers. This review underscores the pressing need for a deeper understanding of sex hormones in cancer therapy and the ensuing implications for future therapeutic innovations.

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Section: Clinical Outcomes and Observationsmentioning

confidence: 99%

Section: Therapeutic Implicationsmentioning

confidence: 99%

Section: Therapeutic Implicationsmentioning

confidence: 99%

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Sex-specific outcomes in cancer therapy: the central role of hormones

Bakhshi,

Ho,

Zanganeh

2024

Front. Med. Technol.

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“…Of note, interest in studying the relationship between PR signaling and DNA damage and repair mechanisms is increasingly emerging. Progesterone has been shown to impact the expression of genes involved in DNA repair pathways, potentially influencing genomic stability, but the mechanism remains still unknown [ 131 ]. Some work suggests that progesterone-activated PRs may modulate the expression of key DNA repair proteins and influence the cellular response to DNA damage [ 132 ].…”

Section: Introductionmentioning

confidence: 99%

Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients

De Lazzari,

Opattova,

Arena

2024

J Exp Clin Cancer Res

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Over the last few decades, the incidence of urogenital cancers has exhibited diverse trends influenced by screening programs and geographical variations. Among women, there has been a consistent or even increased occurrence of endometrial and ovarian cancers; conversely, prostate cancer remains one of the most diagnosed malignancies, with a rise in reported cases, partly due to enhanced and improved screening efforts.Simultaneously, the landscape of cancer therapeutics has undergone a remarkable evolution, encompassing the introduction of targeted therapies and significant advancements in traditional chemotherapy. Modern targeted treatments aim to selectively address the molecular aberrations driving cancer, minimizing adverse effects on normal cells. However, traditional chemotherapy retains its crucial role, offering a broad-spectrum approach that, despite its wider range of side effects, remains indispensable in the treatment of various cancers, often working synergistically with targeted therapies to enhance overall efficacy.For urogenital cancers, especially ovarian and prostate cancers, DNA damage response inhibitors, such as PARP inhibitors, have emerged as promising therapeutic avenues. In BRCA-mutated ovarian cancer, PARP inhibitors like olaparib and niraparib have demonstrated efficacy, leading to their approval for specific indications. Similarly, patients with DNA damage response mutations have shown sensitivity to these agents in prostate cancer, heralding a new frontier in disease management. Furthermore, the progression of ovarian and prostate cancer is intricately linked to hormonal regulation. Ovarian cancer development has also been associated with prolonged exposure to estrogen, while testosterone and its metabolite dihydrotestosterone, can fuel the growth of prostate cancer cells. Thus, understanding the interplay between hormones, DNA damage and repair mechanisms can hold promise for exploring novel targeted therapies for ovarian and prostate tumors.In addition, it is of primary importance the use of preclinical models that mirror as close as possible the biological and genetic features of patients’ tumors in order to effectively translate novel therapeutic findings “from the bench to the bedside”.In summary, the complex landscape of urogenital cancers underscores the need for innovative approaches. Targeted therapy tailored to DNA repair mechanisms and hormone regulation might offer promising avenues for improving the management and outcomes for patients affected by ovarian and prostate cancers.

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Pesticide exposure and oxidative stress generation are linked to poor prognosis outcomes in breast cancer women carrying the allelic variant rs7438135 in the UGT2B7 gene

Vacario,

da Silva,

Machado

et al. 2024

J Biochem & Molecular Tox

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Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q‐PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity—TRAP, and nitric oxide metabolites—NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high‐grade and triple‐negative/Luminal B tumors, and low‐risk stratified patients. TRAP was depleted in young patients at menopause and those with triple‐negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide‐induced oxidative stress generation in BC patients.

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Sex steroid hormones and DNA repair regulation: Implications on cancer treatment responses

Cited by 3 publications

References 153 publications

Sex-specific outcomes in cancer therapy: the central role of hormones

Sex-specific outcomes in cancer therapy: the central role of hormones

Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients

Pesticide exposure and oxidative stress generation are linked to poor prognosis outcomes in breast cancer women carrying the allelic variant rs7438135 in the UGT2B7 gene

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