Redrawing the Lines: The Next Generation of Treatment in Metastatic Breast Cancer

Savard, Marie-France; Khan, Omar; Hunt, Kelly K.; Verma, Sunil

doi:10.1200/edbk_237419

Cited by 25 publications

(25 citation statements)

References 78 publications

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“…In recent years, an upsurge of life-saving treatment advances against BC has been accomplished, thereby creating new optimism. Indeed, there is now an overwhelming choices of treatment options fighting the complex combination of cells in each individual cancer [20]. Here, we introduce in principle the available therapeutic choices for BC treatment, with a brief overview on the most relevant pharmacological ones currently in clinical use.…”

Section: Outline On the Therapeutic Approaches For Bc Treatmentmentioning

confidence: 99%

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Ferraro

Piccolo

Misso

et al. 2020

Cells

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In this review we have showcased the preclinical development of original amphiphilic nanomaterials designed for ruthenium-based anticancer treatments, to be placed within the current metallodrugs approach leading over the past decade to advanced multitarget agents endowed with limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC) interventions, including the triple-negative subtype (TNBC) with poor therapeutic alternatives. BC is currently the second most widespread cancer and the primary cause of cancer death in women. Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced next-generation metallotherapeutics, with NAMI-A and KP1019 as two iconic ruthenium complexes having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently conceived and developed into anticancer drugs demonstrating attractive properties. In this field, we focused on the evaluation of a Ru(III) complex—named AziRu—incorporated into a suite of both zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu inspired by the well-known NAMI-A complex, information on non-nanostructured Ru-based anticancer agents have been included in a precise manner.

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Section: Outline On the Therapeutic Approaches For Bc Treatmentmentioning

confidence: 99%

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Ferraro

Piccolo

Misso

et al. 2020

Cells

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“…For TNBC there are still no specific established therapies due to lack of defined targets, and radio-and chemotherapies are commonly used instead [15]. Additional potential therapeutic targets for personalized therapies have been identified (e.g., PI3KCA, EGFR, PARP, and PDL/PDL-1) [16][17][18]. Gene expression profiling classified BC into different molecular subtypes with distinct features and clinical outcomes: luminal A, luminal B, HER2-enriched, basal-like, claudin-low and normal-like subtypes [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

MAGI1, a New Potential Tumor Suppressor Gene in Estrogen Receptor Positive Breast Cancer

Alday-Parejo

Richard

Wörthmüller

et al. 2020

Cancers

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Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an intracellular adaptor protein that stabilizes epithelial junctions consistent with a tumor suppressive function in several cancers of epithelial origin. Here we report, based on experimental results and human breast cancer (BC) patients’ gene expression data, that MAGI1 is highly expressed and acts as tumor suppressor in estrogen receptor (ER)+/HER2− but not in HER2+ or triple negative breast cancer (TNBC). Within the ER+/HER2− subset, high MAGI1 expression associates with ESR1 and luminal genes GATA3 and FOXA1 expression and better prognosis, while low MAGI1 levels correlates with higher histological grade, more aggressive phenotype and worse prognosis. Experimentally, MAGI1 downregulation in the ER+ human BC cells MCF7 impairs ER expression and signaling, promotes cell proliferation, and reduces apoptosis and epithelial differentiation. MAGI1 downregulation in the ER+ murine BC cell line 67NR accelerates primary tumor growth and enhances experimental lung metastasis formation. MAGI1 expression is upregulated by estrogen/ER, downregulated by prostaglandin E2/COX-2axis, and negatively correlates with inflammation in ER+/HER2− BC patients. Taken together, we show that MAGI1 is a new potential tumor suppressor in ER+/HER2− breast cancer with possible prognostic value for the identification of patients at high-risk of relapse within this subset.

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“…Targeted therapies, that is, use of drugs that inhibit cancer driver genes, has greatly improved patient outcome for several different cancer types in recent years 1‐3 . However, of the approximate 700 identified cancer genes, 4,5 approved treatments are currently available for only approximate 40 6 .…”

Section: Introductionmentioning

confidence: 99%

Drugging “undruggable” genes for cancer treatment: Are we making progress?

Duffy

Crown

2020

Intl Journal of Cancer

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RAS, TP53 (p53) and MYC are among the most frequently altered driver genes in cancer. Thus, RAS is the most frequently mutated oncogene, MYC the most frequently amplified gene and TP53 the most frequently mutated tumor suppressor gene and overall the most frequently mutated gene in cancer. Theoretically, therefore, these genes are highly attractive targets for cancer treatment. However, as the protein products of each of these genes lack an accessible hydrophobic pocket into which low molecular weight compounds might bind with high affinity, they have proved difficult to target and have traditionally been referred to as "undruggable." Despite this branding, several low molecular weight compounds targeting each of these proteins have recently been reported to have anticancer activity in preclinical models. Indeed, several drugs inhibiting mutant KRAS, MYC overexpression or reactivating mutant p53 have undergone or are currently undergoing clinical trials. For targeting mutant KRAS and reactivating mutant p53, trials have progressed to a Phase III stage, that is, the mutant-p53 reactivating drug, APR-246 is currently being investigated in patients with myelodysplastic syndrome (MDS) and the RAS inhibitor, rigosertib is also undergoing evaluation in patients with MDS. Although there appears to be no directly acting MYC inhibitor currently being tested in a clinical trial, an anti-MYC compound, known as OmoMYC has been extensively validated in multiple preclinical models and is being developed for clinical evaluation. Based on current evidence, the traditional perception of RAS, p53 and MYC as being "undruggable" would appear to be coming to an end.

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Redrawing the Lines: The Next Generation of Treatment in Metastatic Breast Cancer

Cited by 25 publications

References 78 publications

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

MAGI1, a New Potential Tumor Suppressor Gene in Estrogen Receptor Positive Breast Cancer

Drugging “undruggable” genes for cancer treatment: Are we making progress?

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