Thermal and Microwave Constrained Focusing for Patient-Specific Breast Cancer Hyperthermia: A Robustness Assessment

The development of new computational approaches that are able to design the correct personalized drugs is the crucial therapeutic issue in cancer research. However, tumor heterogeneity is the main obstacle to developing patient-specific single drugs or combinations of drugs that already exist in clinics. In this study, we developed a computational approach that integrates copy number alteration, gene expression, and a protein interaction network of 73 basal breast cancer samples. 2509 prognostic genes harboring a copy number alteration were identified using survival analysis, and a protein–protein interaction network considering the direct interactions was created. Each patient was described by a specific combination of seven altered hub proteins that fully characterize the 73 basal breast cancer patients. We suggested the optimal combination therapy for each patient considering drug–protein interactions. Our approach is able to confirm well-known cancer related genes and suggest novel potential drug target genes. In conclusion, we presented a new computational approach in breast cancer to deal with the intra-tumor heterogeneity towards personalized cancer therapy.

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Breast cancer hyperthermia using a grid array applicator

2020 SoutheastCon ◽

10.1109/southeastcon44009.2020.9249686 ◽

2020 ◽

Author(s):

Sreekala Suseela ◽

Parveen Wahid

Keyword(s):

Breast Cancer ◽

Cancer Hyperthermia

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Towards integration of 64Cu-DOTA-trastuzumab PET-CT and MRI with mathematical modeling to predict response to neoadjuvant therapy in HER2 + breast cancer

Scientific Reports ◽

10.1038/s41598-020-77397-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Angela M. Jarrett ◽

David A. Hormuth ◽

Vikram Adhikarla ◽

Prativa Sahoo ◽

Daniel Abler ◽

...

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Treatment Response ◽

Growth Factor Receptor ◽

Patient Specific ◽

Mathematical Framework ◽

Breast Cancer Patients ◽

Data Types ◽

Her2 Breast Cancer ◽

Mri Scans

AbstractWhile targeted therapies exist for human epidermal growth factor receptor 2 positive (HER2 +) breast cancer, HER2 + patients do not always respond to therapy. We present the results of utilizing a biophysical mathematical model to predict tumor response for two HER2 + breast cancer patients treated with the same therapeutic regimen but who achieved different treatment outcomes. Quantitative data from magnetic resonance imaging (MRI) and 64Cu-DOTA-trastuzumab positron emission tomography (PET) are used to estimate tumor density, perfusion, and distribution of HER2-targeted antibodies for each individual patient. MRI and PET data are collected prior to therapy, and follow-up MRI scans are acquired at a midpoint in therapy. Given these data types, we align the data sets to a common image space to enable model calibration. Once the model is parameterized with these data, we forecast treatment response with and without HER2-targeted therapy. By incorporating targeted therapy into the model, the resulting predictions are able to distinguish between the two different patient responses, increasing the difference in tumor volume change between the two patients by > 40%. This work provides a proof-of-concept strategy for processing and integrating PET and MRI modalities into a predictive, clinical-mathematical framework to provide patient-specific predictions of HER2 + treatment response.

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Drug-Induced Resistance and Phenotypic Switch in Triple-Negative Breast Cancer Can Be Controlled via Resolution and Targeting of Individualized Signaling Signatures

Cancers ◽

10.3390/cancers13195009 ◽

2021 ◽

Vol 13 (19) ◽

pp. 5009

Author(s):

Swetha Vasudevan ◽

Ibukun A. Adejumobi ◽

Heba Alkhatib ◽

Sangita Roy Chowdhury ◽

Shira Stefansky ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Growth Factor Receptor ◽

Patient Specific ◽

Network Structures ◽

Breast Cancers ◽

Drug Induced ◽

Tcga Dataset

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancers which is treated mainly with chemotherapy and radiotherapy. Epidermal growth factor receptor (EGFR) was considered to be frequently expressed in TNBC, and therefore was suggested as a therapeutic target. However, clinical trials of EGFR inhibitors have failed. In this study, we examine the relationship between the patient-specific TNBC network structures and possible mechanisms of resistance to anti-EGFR therapy. Using an information-theoretical analysis of 747 breast tumors from the TCGA dataset, we resolved individualized protein network structures, namely patient-specific signaling signatures (PaSSS) for each tumor. Each PaSSS was characterized by a set of 1–4 altered protein–protein subnetworks. Thirty-one percent of TNBC PaSSSs were found to harbor EGFR as a part of the network and were predicted to benefit from anti-EGFR therapy as long as it is combined with anti-estrogen receptor (ER) therapy. Using a series of single-cell experiments, followed by in vivo support, we show that drug combinations which are not tailored accurately to each PaSSS may generate evolutionary pressure in malignancies leading to an expansion of the previously undetected or untargeted subpopulations, such as ER+ populations. This corresponds to the PaSSS-based predictions suggesting to incorporate anti-ER drugs in certain anti-TNBC treatments. These findings highlight the need to tailor anti-TNBC targeted therapy to each PaSSS to prevent diverse evolutions of TNBC tumors and drug resistance development.

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Multiomics analysis of serial PARP inhibitor treated metastatic TNBC inform on rational combination therapies

npj Precision Oncology ◽

10.1038/s41698-021-00232-w ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Marilyne Labrie ◽

Allen Li ◽

Allison Creason ◽

Courtney Betts ◽

Jamie Keck ◽

...

Keyword(s):

Breast Cancer ◽

Parp Inhibitor ◽

Parp Inhibitors ◽

Parp Inhibition ◽

Patient Specific ◽

Combination Therapies ◽

Breast Cancer Patients ◽

Effector Cells ◽

Basal Breast Cancer ◽

Rational Combination

AbstractIn a pilot study, we evaluated the feasibility of real-time deep analysis of serial tumor samples from triple negative breast cancer patients to identify mechanisms of resistance and treatment opportunities as they emerge under therapeutic stress engendered by poly-ADP-ribose polymerase (PARP) inhibitors (PARPi). In a BRCA-mutant basal breast cancer exceptional long-term survivor, a striking tumor destruction was accompanied by a marked infiltration of immune cells containing CD8 effector cells, consistent with pre-clinical evidence for association between STING mediated immune activation and benefit from PARPi and immunotherapy. Tumor cells in the exceptional responder underwent extensive protein network rewiring in response to PARP inhibition. In contrast, there were minimal changes in the ecosystem of a luminal androgen receptor rapid progressor, likely due to indifference to the effects of PARP inhibition. Together, identification of PARPi-induced emergent changes could be used to select patient specific combination therapies, based on tumor and immune state changes.

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Therapeutic Potential of Lymphoid Infiltrates in Breast Cancer

Current Medicinal Chemistry ◽

10.2174/0929867328666210430132701 ◽

2021 ◽

Vol 28 ◽

Author(s):

Xiao-Yang Chen ◽

Puay Hoon Tan

Keyword(s):

Breast Cancer ◽

Immune Response ◽

Immune System ◽

Therapeutic Potential ◽

Antibody Therapy ◽

Tumour Microenvironment ◽

Current Treatment ◽

Adoptive Cell Transfer ◽

Treatment Modalities ◽

Patient Specific

: Despite diagnostic and therapeutic advances in breast cancer, it remains the most frequently diagnosed malignancy in females, with the highest cancer-related mortality rate in women globally. With an improved understanding of the complex interactions between breast cancer and the immune system, immunotherapy has shown great potential in clinical management, potentially adding to current treatment modalities. These immunotherapeutic approaches include adoptive cell transfer therapy, cancer vaccination, monoclonal antibody therapy, and oncolytic virus therapy. Depending on the immune cells and cytokines present, the tumour microenvironment (TME) can be immunosuppressive or favourable for mounting an immune response. Effector lymphocytes play an essential role during an anticancer immune response, but their activities can be suppressed by the hostile TME. Many studies have made good progress in the modulation of the immune response to allow the identification and elimination of tumour cells. However, the efficacy of these immunotherapies is patient-specific and highly dependent on the immunological profile of the tumour and its TME. This review will give an overview of breast cancer, the immune system as well as their complex relationship. Strategies and approaches that can harness the potential of immunotherapy that engages lymphocytes in the treatment of breast cancer, along with their current challenges, will also be discussed.

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