The Genetic Complexity of Prostate Cancer

Compérat, Éva; Wasinger, Gabriel; Oszwald, André; Kain, Renate; Cancel‐Tassin, Géraldine; Cussenot, Olivier

doi:10.3390/genes11121396

Cited by 9 publications

(8 citation statements)

References 65 publications

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“…Both enzymes, the transmembrane angiotensinconverting enzyme 2 (ACE2) and the transmembrane protease, serine 2 (TMPRSS2) regulate SARS-CoV-2 invasion through cell membrane [4,5]. These enzymes are androgen-dependent and can be strongly upregulated by elevated levels of androgens [4,6]. Moreover, the expression of TMPRSS2 is found in the lung, gastrointestinal system, and heart [4,6].…”

Section: Introductionmentioning

confidence: 99%

“…These enzymes are androgen-dependent and can be strongly upregulated by elevated levels of androgens [4,6]. Moreover, the expression of TMPRSS2 is found in the lung, gastrointestinal system, and heart [4,6]. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland [4] during prostate carcinogenesis, are regulated by androgens.…”

Section: Introductionmentioning

confidence: 99%

“…Androgen deprivation therapy (ADT) and the secondgeneration androgen receptor (AR) targeting therapy were developed to suppress the androgen-activated intracellular cascade that leads to tumor progression and aggressive tumor growth [6]. Several trials are currently evaluating androgen suppression in patients with SARS-CoV-2 infection with a focus on coronavirus disease 2019 (COVID- 19) disease severity [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis

et al. 2021

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Purpose Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT). Methods We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane’s Q test and I2 statistic, respectively. Results Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44–1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9–1.68). Conclusion We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis

et al. 2021

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“…In the complex genomic landscape of PCa, the PI3K-AKT-mTOR pathway is one of the most frequently activated signaling pathways and PTEN one of the most consistently altered genes. Indeed, PTEN loss is associated with events occurring early in PCa development, and is strongly linked to advanced PCa progression and poor clinical outcome (33). In addition to its role in the PI3K pathway, PTEN plays an important role in the regulation of the tumor microenvironment cross-talk, DNA damage, immune response and inflammation (34).…”

Section: Discussionmentioning

confidence: 99%

HER2 Mediates PSMA/mGluR1-Driven Resistance to the DS-7423 Dual PI3K/mTOR Inhibitor in PTEN Wild-type Prostate Cancer Models

Gómez

Galazi

Weitsman

et al. 2022

Molecular Cancer Therapeutics

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Prostate cancer remains a major cause of male mortality. Genetic alteration of the PI3K/AKT/mTOR pathway is one of the key events in tumor development and progression in prostate cancer, with inactivation of the PTEN tumor suppressor being very common in this cancer type. Extensive evaluation has been performed on the therapeutic potential of PI3K/AKT/mTOR inhibitors and the resistance mechanisms arising in patients with PTEN mutant background. However, in patients with a PTEN wild type phenotype, PI3K/AKT/mTOR inhibitors have not demonstrated efficacy and this remains an area of clinical unmet need. In this study, we have investigated the response of PTEN wild-type prostate cancer cell lines to the dual PI3K/mTOR inhibitor DS-7423 alone or in combination with HER2 inhibitors or mGluR1 inhibitors. Upon treatment with the dual PI3K/mTOR inhibitor DS-7423, PTEN wild-type prostate cancer CWR22/22RV1 cells upregulate expression of the proteins PSMA, mGluR1 and the tyrosine kinase receptor HER2, while PTEN mutant LNCaP cells upregulate androgen receptor and HER3. PSMA, mGluR1 and HER2 exert control over one another in a positive feedback loop that allows cells to overcome treatment with DS-7423. Concomitant targeting of PI3K/mTOR with either HER2 or mGluR1 inhibitors results in decreased cell survival and tumor growth in xenograft studies. Our results suggest a novel therapeutic possibility for PTEN wild-type-PI3K/AKT mutant prostate cancer patients based in the combination of PI3K/mTOR blockade with HER2 or mGluR1 inhibitors.

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“…Prostate cancer (PC) is the most common cancer in men and the second most prevalent cause of cancer-related death worldwide [ 1 ]. Despite recent major breakthroughs in the treatment, PC remains a major public health concern, with more than 1.1 million cases worldwide detected every year.…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets

Ioannidou

Moschetta

Shah

et al. 2021

IJMS

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Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory castration-resistant PC (CRPC) have demonstrated increased toxicity with no clinical benefit. A better understanding of the mechanism of angiogenesis may help to understand the failure of trials, possibly leading to the development of new targeted anti-angiogenic therapies in PC. These could include the identification of specific subsets of patients who might benefit from these therapeutic strategies. This paper provides a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on anti-angiogenic agents and the potential mechanisms of resistance.

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The Genetic Complexity of Prostate Cancer

Cited by 9 publications

References 65 publications

Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis

Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis

HER2 Mediates PSMA/mGluR1-Driven Resistance to the DS-7423 Dual PI3K/mTOR Inhibitor in PTEN Wild-type Prostate Cancer Models

Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets

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