Novel combinatorial strategies for boosting the efficacy of immune checkpoint inhibitors in advanced breast cancers

Tolba, Mai F.; Elghazaly, Hesham; Bousoik, Emira; Elmazar, Mohamed M.; Tolaney, Sara M.

doi:10.1007/s12094-021-02613-w

Cited by 18 publications

(13 citation statements)

References 114 publications

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“…Kinase inhibitor drugs have been used in different breast cancer research and clinical trials, especially for TNBC, and they are considered one of the most successful targeted therapies for cancer [ 126 , 127 ]. They were used as a monotherapy and combined therapy for TNBC, and they are considered a promising strategy to treat advanced TNBC [ 128 ]. As a monotherapy, a tyrosine kinase inhibitor effectively inhibits the proliferation and induced autophagy and apoptosis in TNBC cells [ 129 ].…”

Section: Resultsmentioning

confidence: 99%

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

Al-Taie

Hannink

Mitchem

et al. 2021

Cancers

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Breast cancer (BC) is the leading cause of death among female patients with cancer. Patients with triple-negative breast cancer (TNBC) have the lowest survival rate. TNBC has substantial heterogeneity within the BC population. This study utilized our novel patient stratification and drug repositioning method to find subgroups of BC patients that share common genetic profiles and that may respond similarly to the recommended drugs. After further examination of the discovered patient subgroups, we identified five homogeneous druggable TNBC subgroups. A drug repositioning algorithm was then applied to find the drugs with a high potential for each subgroup. Most of the top drugs for these subgroups were chemotherapy used for various types of cancer, including BC. After analyzing the biological mechanisms targeted by these drugs, ferroptosis was the common cell death mechanism induced by the top drugs in the subgroups with neoplasm subdivision and race as clinical variables. In contrast, the antioxidative effect on cancer cells was the common targeted mechanism in the subgroup of patients with an age less than 50. Literature reviews were used to validate our findings, which could provide invaluable insights to streamline the drug repositioning process and could be further studied in a wet lab setting and in clinical trials.

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Section: Resultsmentioning

confidence: 99%

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

Al-Taie

Hannink

Mitchem

et al. 2021

Cancers

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“…Checkpoint inhibitors used in clinical practice for BC target either the PD-1 receptor or the PD-L1 ligand. The disruption of PD-1/PD-L1 interaction enhances the ability of T cells to attack the tumor [53]. The U.S. Food and Drug Administration (FDA) (https://www.fda.gov/, accessed on 14 November 2021) recently (in 2019) approved atezolizumab (anti-PD-L1 antibody) with paclitaxel as a combination therapy for PD-L1-positive unresectable locally advanced or metastatic TNBC [54].…”

Section: Immune Checkpoint Inhibition (Ici) Anti-her2 Antibodies and ...mentioning

confidence: 99%

Peripheral Blood Transcriptome in Breast Cancer Patients as a Source of Less Invasive Immune Biomarkers for Personalized Medicine, and Implications for Triple Negative Breast Cancer

Čelešnik

Potočnik

2022

Cancers

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Transcriptome studies of peripheral blood cells can advance our understanding of the systemic immune response to the presence of cancer and the mechanisms underlying cancer onset and progression. This enables the identification of novel minimally invasive immune biomarkers for early cancer detection and personalized cancer management and may bring forward new immunotherapy options. Recent blood gene expression analyses in breast cancer (BC) identified distinct patient subtypes that differed in the immune reaction to cancer and were distinct from the clinical BC subtypes, which are categorized based on expression of specific receptors on tumor cells. Introducing new BC subtypes based on peripheral blood gene expression profiles may be appropriate, since it may assist in BC prognosis, the identification of patients likely to benefit from immunotherapy, and treatment efficacy monitoring. Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous, and difficult-to-treat disease, and identification of novel biomarkers for this BC is crucial for clinical decision-making. A few studies have reported TNBC-enriched blood transcriptional signatures, mostly related to strong inflammation and augmentation of altered immune signaling, that can differentiate TNBC from other classical BC subtypes and facilitate diagnosis. Future research is geared toward transitioning from expression signatures in unfractionated blood cells to those in immune cell subpopulations.

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“…Initial work exploring immunotherapy focused on triple-negative breast cancer (TNBC) since it was known to have higher rates of PD-L1 expression, higher prevalence of tumor-infiltrating lymphocytes (TILs), and higher mutational burden ( 1 ). Clinical trials for antibodies targeting PD-1/PD-L1 in metastatic TNBC have demonstrated promising therapeutic outcomes ( 1 , 2 ). Despite a very modest response rate to checkpoint inhibition as monotherapy in TNBC, patients who achieved response were found to have prolonged overall survival ( 1 ).…”

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confidence: 99%

“…While there is a benefit in adding checkpoint inhibitors to chemotherapy in TNBC, not all patients respond to immunotherapy. This has underscored the need for novel strategies to expand the benefits of checkpoint inhibitors for broader populations of patients including patients with advanced hormone receptor-positive (HR+) BC as well as HER-2 positive tumors that are refractory to the standard therapy ( 2 ). Early data generated from immunotherapy studies with those other BC subtypes showed clues of improved therapeutic outcomes potentially within certain subsets of patients ( 2 ).…”

mentioning

confidence: 99%

“…This has underscored the need for novel strategies to expand the benefits of checkpoint inhibitors for broader populations of patients including patients with advanced hormone receptor-positive (HR+) BC as well as HER-2 positive tumors that are refractory to the standard therapy ( 2 ). Early data generated from immunotherapy studies with those other BC subtypes showed clues of improved therapeutic outcomes potentially within certain subsets of patients ( 2 ). There are therefore several registration studies for early-stage HR+ disease along with early and advanced HER2+ disease.…”

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confidence: 99%

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Editorial: Immunotherapy as an Evolving Approach for the Treatment of Breast Cancer

et al. 2021

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Novel combinatorial strategies for boosting the efficacy of immune checkpoint inhibitors in advanced breast cancers

Cited by 18 publications

References 114 publications

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

Peripheral Blood Transcriptome in Breast Cancer Patients as a Source of Less Invasive Immune Biomarkers for Personalized Medicine, and Implications for Triple Negative Breast Cancer

Editorial: Immunotherapy as an Evolving Approach for the Treatment of Breast Cancer

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