Periodic Reporting for period 2 - CancerADAPT (Targeting the adaptive capacity of prostate cancer through the manipulation of transcriptional and metabolic traits)
Reporting period: 2021-05-01 to 2022-10-31
The mission of CancerADAPT is to identify key vulnerabilities of prostate cancer by applying an innovative perspective of the biological process of prostate cancer progression. As stated in the original proposal “CancerADAPT will help decipher the mechanisms by which cancer cells adapt to hostile environments existing in our body”. Knowing which are the strategies that cancer cells exploit to survive and growth in our body is a fundamental step to design rational therapeutic strategies with greater clinical benefit. Decades of modern cancer research has revealed that cancers are highly plastic and adaptive entities, that are in continuous change, and that can also remodel the niche they inhabit to ensure their survival and growth. As such, we propose that targeting the adaptability of tumour cells will represent an innovative therapeutic strategy for modern cancer medicine. CancerADAPT focuses on metabolism as the cornerstone of prostate cancer adaptability, and deploys state-of-the-art technologies and concepts in order to provide a change in the paradigm of current prostate cancer management.
The benefit for society emanates from its innovative perspective to undertake such a societal challenge. We believe that only the fundamental understanding of the biological processes underlying cancer biology can lead to the identification of innovative combinatorial therapies. In the context of this proposal, we aim to tackle cancer treatment applying ecology and evolutionary concepts to reduce the adaptability and plasticity of tumors.
The benefit for society emanates from its innovative perspective to undertake such a societal challenge. We believe that only the fundamental understanding of the biological processes underlying cancer biology can lead to the identification of innovative combinatorial therapies. In the context of this proposal, we aim to tackle cancer treatment applying ecology and evolutionary concepts to reduce the adaptability and plasticity of tumors.
During this first period of the proposal we have exploited computational biology to identify key molecular determinants of prostate cancer progression. In turn, we have finalized and published relevant stories describing our results, we have contributed to the development of complementary projects by our collaborators and have exciting ongoing projects that will have a significant impact on our understanding of prostate cancer adaptation.
CancerADAPT has given us the opportunity to attract and train outstanding young researchers, to acquire and exploit innovative technologies, and to push the boundaries of our comprehension of tumor cell biology.
In short, we have made significant progress in the following areas:
- Exploiting public datasets to identify potential mediators of prostate cancer progression. In the advent of modern sequencing technologies, international groups and consortia have sequence large cohorts of prostate cancers with rich clinical annotation. This data is publicly available, and we have exploited it using advanced computational strategies in order to identify molecular events that are consistently altered in recurrent of metastatic disease. Some of these candidates have been proven to regulate cancer cell biology and are current subjects of study in the lab.
- Identifying effectors of androgen signaling and adaptation to androgen deprivation. Prostate cancer patients are frequently treated with androgen-deprivation therapies once they fail to respond to first line treatments. However, resistance often emerges, leading to castration-resistant prostate cancer. We have studied metabolic processes regulated by androgens to shed light on the mechanism that might lead to resistance to androgen deprivation therapies. Some of these studies have been published in international journals and presented in conferences, and received recognitions in the form of best poster communication.
- Unraveling the mechanism of action of key metabolic drivers of prostate cancer progression. The lab is recognized by its seminal work in methionine metabolism, a molecular process that is deregulated in cancer and required for proper cell function. Our ongoing work has identified key regulators and effectors of methionine metabolism that explain the role of these metabolites in prostate cancer cell adaptation, as a critical effort to refine and improve the use of drugs targeting this pathway. In addition, we have demonstrated and published that the same molecular strategy that cancer cells use to hijack methionine metabolism is relevant beyond cancer to ensure a healthy organismal homeostasis.
CancerADAPT has given us the opportunity to attract and train outstanding young researchers, to acquire and exploit innovative technologies, and to push the boundaries of our comprehension of tumor cell biology.
In short, we have made significant progress in the following areas:
- Exploiting public datasets to identify potential mediators of prostate cancer progression. In the advent of modern sequencing technologies, international groups and consortia have sequence large cohorts of prostate cancers with rich clinical annotation. This data is publicly available, and we have exploited it using advanced computational strategies in order to identify molecular events that are consistently altered in recurrent of metastatic disease. Some of these candidates have been proven to regulate cancer cell biology and are current subjects of study in the lab.
- Identifying effectors of androgen signaling and adaptation to androgen deprivation. Prostate cancer patients are frequently treated with androgen-deprivation therapies once they fail to respond to first line treatments. However, resistance often emerges, leading to castration-resistant prostate cancer. We have studied metabolic processes regulated by androgens to shed light on the mechanism that might lead to resistance to androgen deprivation therapies. Some of these studies have been published in international journals and presented in conferences, and received recognitions in the form of best poster communication.
- Unraveling the mechanism of action of key metabolic drivers of prostate cancer progression. The lab is recognized by its seminal work in methionine metabolism, a molecular process that is deregulated in cancer and required for proper cell function. Our ongoing work has identified key regulators and effectors of methionine metabolism that explain the role of these metabolites in prostate cancer cell adaptation, as a critical effort to refine and improve the use of drugs targeting this pathway. In addition, we have demonstrated and published that the same molecular strategy that cancer cells use to hijack methionine metabolism is relevant beyond cancer to ensure a healthy organismal homeostasis.
Our research has unraveled potential processes that underlie the adaptation of prostate cancer cells to hostile environments during the process of disease progression.
Our aim for the next period of the proposal is to decipher the mechanism of action of such processes, and to translate this information into biomarkers or therapeutic strategies that redefine prostate cancer patient management. In addition, our research will provide biological understanding beyond the framework of cancer, to shed light into the regulatory mechanism of organism pathophysiology.
Our aim for the next period of the proposal is to decipher the mechanism of action of such processes, and to translate this information into biomarkers or therapeutic strategies that redefine prostate cancer patient management. In addition, our research will provide biological understanding beyond the framework of cancer, to shed light into the regulatory mechanism of organism pathophysiology.