Clinicogenomic characterization of prostate cancer liver metastases

Alshalalfa, Mohammed; Seldon, Crystal; Franco, Idalid; Vince, Randy; Carmona, Ruben; Punnen, Sanoj; Kaochar, Salma; Dess, Robert T.; Kishan, Amar U.; Spratt, Daniel E.; Sharma, Janaki; Pra, Alan Dal; Pollack, Alan; Abramowitz, Matthew C.; Mahal, Brandon A.

doi:10.1038/s41391-021-00486-2

Cited by 11 publications

(11 citation statements)

References 11 publications

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“…On the other hand, PCa is the most prevalent non-skin cancer identified in males, ranging from a localized, indolent progression to a quickly developing, metastatic malignancy [ 162 ]. Untreated PCa patients are predicted to have a high mortality rate due to the increased risk of metastasis, such as liver metastases [ 163 ]. Ethnicity, age, family history, and IGF all have a recognized role in cancer pathogenesis.…”

Section: Autophagy and Aging-related Conditionsmentioning

confidence: 99%

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view

Raee,

Tan,

Najafi

et al. 2023

Reprod Biol Endocrinol

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Autophagy is a highly conserved, lysosome-dependent biological mechanism involved in the degradation and recycling of cellular components. There is growing evidence that autophagy is related to male reproductive biology, particularly spermatogenic and endocrinologic processes closely associated with male sexual and reproductive health. In recent decades, problems such as decreasing sperm count, erectile dysfunction, and infertility have worsened. In addition, reproductive health is closely related to overall health and comorbidity in aging men. In this review, we will outline the role of autophagy as a new player in aging male reproductive dysfunction and prostate cancer. We first provide an overview of the mechanisms of autophagy and its role in regulating male reproductive cells. We then focus on the link between autophagy and aging-related diseases. This is followed by a discussion of therapeutic strategies targeting autophagy before we end with limitations of current studies and suggestions for future developments in the field.

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Section: Autophagy and Aging-related Conditionsmentioning

confidence: 99%

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view

Raee,

Tan,

Najafi

et al. 2023

Reprod Biol Endocrinol

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“…Liver metastasis is associated with some of the worst clinical outcomes compared with other sites [ 32 , 33 ]. Out of all the patient with liver metastasis, those which originated from the prostate have the second worse survival (behind testicular cancer) [ 34 ].…”

Section: Prostate Metastasis To the Livermentioning

confidence: 99%

“…Compared to other metastatic sites for PCa, liver metastases reportedly have the highest fraction of genomic alterations and there are also potential liver specific alterations such as MYC amplification, PTEN deletion or PIK3CB amplification [ 33 ]. PCa may undergo site specific transcriptional changes, whereby the tumors adapt to survive and thrive in that specific micro-environment, and it may be that the changes in metabolism pathways are especially important to PCa that have located to the liver [ 38 , 39 ].…”

Section: Prostate Metastasis To the Livermentioning

confidence: 99%

Liver Microenvironment Response to Prostate Cancer Metastasis and Hormonal Therapy

Buxton

Abbasova

Bevan

et al. 2022

Cancers

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Prostate cancer-associated deaths arise from disease progression and metastasis. Metastasis to the liver is associated with the worst clinical outcomes for prostate cancer patients, and these metastatic tumors can be particularly resistant to the currently widely used chemotherapy and hormonal therapies, such as anti-androgens which block androgen synthesis or directly target the androgen receptor. The incidence of liver metastases is reportedly increasing, with a potential correlation with use of anti-androgen therapies. A key player in prostate cancer progression and therapeutic response is the microenvironment of the tumor(s). This is a dynamic and adaptive collection of cells and proteins, which impart signals and stimuli that can alter biological processes within prostate cancer cells. Investigation in the prostate primary site has demonstrated that cells of the microenvironment are also responsive to hormones and hormonal therapies. In this review, we collate information about what happens when cancer moves to the liver: the types of prostate cancer cells that metastasize there, the response of resident mesenchymal cells of the liver, and how the interactions between the cancer cells and the microenvironment may be altered by hormonal therapy.

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“…In fact, the hazard ratio of death from PCLM is the highest compared to LM from other tumor types [17]. In addition, PC patients are often not routinely screened for visceral metastasis such as LM, and LM does not seem to respond as well to conventional therapies, such as hormonal or chemotherapy, that are successfully used to treat other metastatic sites of mCRPC [17][18][19][20]. While PC visceral metastasis in 2 of 13 general renders an unfavourable prognosis, patients with LM have much worse outcomes than those with lung metastases, regardless of treatment [20,21].…”

Section: Introductionmentioning

confidence: 97%

“…This is highly problematic as the liver is the most lethal metastatic site of mCRPC, being associated with a median overall survival of 10 to 14 months [10,[13][14][15][16]. In fact, the hazard ratio of death from PCLM is the highest compared to LM from other tumor types [17]. In addition, PC patients are often not routinely screened for visceral metastasis such as LM, and LM does not seem to respond as well to conventional therapies, such as hormonal or chemotherapy, that are successfully used to treat other metastatic sites of mCRPC [17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Prostate Cancer Liver Metastasis: An Ominous Metastatic Site in Need of Distinct Management Strategies

Shiner,

Sperandio,

Naimi

et al. 2024

JCM

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Prostate cancer liver metastasis (PCLM), seen in upwards of 25% of metastatic castration-resistant PC (mCRPC) patients, is the most lethal site of mCRPC with a median overall survival of 10–14 months. Despite its ominous prognosis and anticipated rise in incidence due to longer survival with contemporary therapy, PCLM is understudied. This review aims to summarize the existing literature regarding the risk factors associated with the development of PCLM, and to identify areas warranting further research. A literature search was conducted through Ovid MEDLINE from 2000 to March 2023. Relevant subject headings and text words were used to capture the following concepts: “Prostatic Neoplasms”, “Liver Neoplasms”, and “Neoplasm Metastasis”. Citation searching identified additional manuscripts. Forty-one studies were retained for detailed analysis. The clinical risk factors for visceral/liver metastasis included <70 years, ≥T3 tumor, N1 nodal stage, de novo metastasis, PSA >20 ng/mL, and a Gleason score >8. Additional risk factors comprised elevated serum AST, LDH or ALP, decreased Hb, genetic markers like RB1 and PTEN loss, PIK3CB and MYC amplification, as well as numerous PC treatments either acting directly or indirectly through inducing liver injury. Further research regarding predictive factors, early detection strategies, and targeted therapies for PCLM are critical for improving patient outcomes.

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Clinicogenomic characterization of prostate cancer liver metastases

Cited by 11 publications

References 11 publications

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view

Liver Microenvironment Response to Prostate Cancer Metastasis and Hormonal Therapy

Prostate Cancer Liver Metastasis: An Ominous Metastatic Site in Need of Distinct Management Strategies

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