Summarize the key findings on cancer ecosystems, drug therapy, immune response, pressure points and all the recent drug therapies used to target the tumor ecosystem or the microenvironment of the tumor including the protein-protein interactions and genomic mutations or sequencing that takes place in a cancer patient.
The short term of response to therapy for most patients is due to a major degree to the almost inevitable emergence of resistance. We have used PARP inhibitors as an effective emerging therapy to explore genomic and adaptive mechanisms of resistance.
Please summarize the current therapies being used to target the cancer or tumor ecosystems.
The different disease states are being treated through the ecosystem methodology that focuses on the surrounding microenvironment.
Understanding the factors that affect the normalization of the tumor environment.
Tumour ecosystems are increasingly recognized as major determinants of treatment response2
and we hypothesized that improved prediction models need to account for tumours as complex ecosystems,
comprising communities of malignant clones within a microenvironment
of stromal, vascular and immune cell types that are perturbed by therapy. Giving extra attention to the breast cancer or tumor ecosystem and types of medications.
Discuss the latest findings from the article:
Treatment landscape of triple-negative breast cancer — expanded options, evolving needs
Giampaolo Bianchini,
Carmine De Angelis,
Luca Licata &
Luca Gianni
Nature Reviews Clinical Oncology volume 19, pages91–113 (2022)Cite this article
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Abstract
Tumour heterogeneity and a long-standing paucity of effective therapies other than chemotherapy have contributed to triple-negative breast cancer (TNBC) being the subtype with the least favourable outcomes. In the past few years, advances in omics technologies have shed light on the relevance of the TNBC microenvironment heterogeneity, unveiling a close dynamic relationship with cancer cell features. An improved understanding of tumour–immune system co-evolution supports the need to adopt a more comprehensive view of TNBC as an ecosystem that encompasses the intrinsic and extrinsic features of cancer cells. This new appreciation of the biology of TNBC has already led to the development of novel targeted agents, including PARP inhibitors, antibody–drug conjugates and immune-checkpoint inhibitors, which are revolutionizing the therapeutic landscape and providing new opportunities both for patients with early-stage TNBC and for those with advanced-stage disease. The current therapeutic scenario is only the tip of the iceberg, as hundreds of new compounds and combinations are in development. The translation of these experimental therapies into clinical benefit is a welcome and ongoing challenge. In this Review, we describe the current and upcoming therapeutic landscape of TNBC and discuss how an integrated view of the TNBC ecosystem can define different levels of risk and provide improved opportunities for tailoring treatment.
Key points
Improved understanding of the interplay between triple-negative breast cancer (TNBC) tumour cells and their microenvironment supports the adoption of a new comprehensive view of this cancer type as an ecosystem.
Tumour–immune co-evolution from early-stage disease through to the metastatic process is accompanied by profound changes in immune cell dynamics that explain variations in the activity of immune-checkpoint inhibitors in different disease settings.
Chemotherapy remains the reference treatment of TNBC, although the optimal use of platinum-based agents, dose-dense therapy and post-neoadjuvant capecitabine remains to be clarified.
Targeted agents, such as PARP inhibitors and antibody–drug conjugates, are established additions in the therapeutic landscape of TNBC.
The key role of immune-checkpoint inhibitors in the treatment of TNBC is being defined and a plethora of ongoing trials testing different combination approaches will provide additional insights to improve the efficacy of immunotherapy.
The application of a breast cancer immunogram describing the TNBC ecosystem will help to successfully implement precision immunology and fulfil the promise of immunotherapy in TNBC.
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