scholarly journals A filter-flow perspective of hematogenous metastasis offers a non-genetic paradigm for personalized cancer therapy

2013 ◽  
Author(s):  
Jacob G Scott ◽  
Alexander G Fletcher ◽  
Philip K Maini ◽  
Alexander R A Anderson ◽  
Philip Gerlee
Keyword(s):  
Metastatic Disease ◽  
Efficiency Index ◽  
Rational Method ◽  
Hematogenous Metastasis ◽  
Primary Target ◽  
Large Dataset ◽  
Oligometastatic Disease ◽  
Metastatic Patterns ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

Background: Research into mechanisms of hematogenous metastasis has largely become genetic in focus, attempting to understand the molecular basis of `seed-soil' relationships. However, preceding this biological mechanism is the physical process of dissemination of circulating tumour cells (CTCs) in the circulatory network. We utilize a novel, network perspective of hematogenous metastasis and a large dataset on metastatic patterns to shed new light on this process. %a fundamental gap in our knowledge of this process. Experimental Design: The metastatic efficiency index (MEI), previously suggested by Weiss, quantifies the process of hematogenous metastasis by taking the ratio of metastatic incidence for a given primary-target organ pair and the relative blood flow between the two sites. In this paper we extend the methodology by taking into account the reduction in CTC number that occurs in capillary beds and a novel network model of CTC flow. Results: By applying this model to a dataset of metastatic incidence, we show that the MEI depends strongly on the assumptions of micrometastatic lesions in the lung and liver. Utilizing this framework we can represent different configurations of metastatic disease and offer a rational method for identifying patients with oligometastatic disease for inclusion in future trials. Conclusions:We show that our understanding of the dynamics of CTC flow is significantly lacking, and that this specifically precludes our ability to predict metastatic patterns in individual patients. Our formalism suggests an opportunity to go a step further in metastatic disease characterization by including the distribution of CTCs at staging, offering a rational method of trial design for oligometastatic disease.

Oncogenomics and CYP450 Implications in Personalized Cancer Therapy

2020 ◽  
Vol 17 (2) ◽  
pp. 104-113
Author(s):  
G.K. Udayaraja ◽  
I. Arnold Emerson
Keyword(s):  
Cytochrome P450 ◽  
Cancer Treatment ◽  
Cancer Susceptibility ◽  
Mutant Gene ◽  
Genome Project ◽  
Interdisciplinary Field ◽  
Precision Therapy ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer ◽  
Genetic Events

Background: The Human Genome Project has unleashed the power of genomics in clinical practice as a choice of individualized therapy, particularly in cancer treatment. Pharmacogenomics is an interdisciplinary field of genomics that deals with drug response, based on individual genetic makeup. Objective: The main genetic events associated with carcinogenesis activate oncogenes or inactivate tumor-suppressor genes. Therefore, drugs should be specific to inactivate or regulate these mutant genes and their protein products for effective cancer treatment. In this review, we summarize how polymedication decisions in cancer treatments based on the evaluation of cytochrome P450 (CYP450) polymorphisms are applied for pharmacogenetic assessment of anticancer therapy outcomes. Results: However, multiple genetic events linked, inactivating a single mutant gene product, may be insufficient to inhibit tumor progress. Thus, genomics and pharmacogenetics directly influence a patient’s response and aid in guiding clinicians to select the safest and most effective combination of medications for a cancer patient from the initial prescription. Conclusion: This review outlines the roles of oncogenes, the importance of cytochrome P450 (CYP450) in cancer susceptibility, and its impact on drug metabolism, proposing combined approaches to achieve precision therapy.

scholarly journals Making the Most of Complexity to Create Opportunities: Comprehensive Genomic Profiling and Molecular Tumor Board for Patients with Non-Small Cell Lung Cancer (NSCLC)

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 609
Author(s):  
Caterina Fumagalli ◽  
Elena Guerini-Rocco ◽  
Massimo Barberis
Keyword(s):  
Lung Cancer ◽  
Small Cell ◽  
Tumor Board ◽  
Genomic Profiling ◽  
Small Cell Lung ◽  
Molecular Alterations ◽  
Comprehensive Genomic Profiling ◽  
Molecular Tumor Board ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

Personalized cancer therapy matches the plan of treatment with specific molecular alterations [...]

scholarly journals 3D Bioprinted cancer models: Revolutionizing personalized cancer therapy

2021 ◽  
Vol 14 (4) ◽  
pp. 101015
Author(s):  
Robin Augustine ◽  
Sumama Nuthana Kalva ◽  
Rashid Ahmad ◽  
Alap Ali Zahid ◽  
Shajia Hasan ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Models ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

Imaging of TKI–Target Interactions for Personalized Cancer Therapy

2012 ◽  
Vol 93 (3) ◽  
pp. 239-241 ◽  
Author(s):  
A J Poot ◽  
P Slobbe ◽  
N H Hendrikse ◽  
A D Windhorst ◽  
GAMS van Dongen
Keyword(s):  
Cancer Therapy ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

Sequencing Approaches for Personalized Cancer Therapy Selection in Pathology

2019 ◽  
pp. 432-438
Author(s):  
Wendy de Leng ◽  
Manon Huibers ◽  
John Hinrichs ◽  
Edwin Cuppen ◽  
Stefan Willems
Keyword(s):  
Cancer Therapy ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

scholarly journals Palliative esophagectomy in unexpected metastatic disease: sense or nonsense?

2018 ◽  
Vol 26 (7) ◽  
pp. 552-557 ◽  
Author(s):  
Lieven P Depypere ◽  
Johnny Moons ◽  
Toni E Lerut ◽  
Willy Coosemans ◽  
Hans Van Veer ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Lymph Nodes ◽  
Metastatic Disease ◽  
Palliative Resection ◽  
Oligometastatic Disease ◽  
Group 3 ◽  
Group 2 ◽  
Curative Esophagectomy ◽  
Group 1 ◽  
Single Organ

Background Despite integrated positron emission tomography and computed tomography screening before and after neoadjuvant treatment in patients with locally advanced esophageal cancer, unexpected metastatic disease is still found in some patients during surgery. Should then esophagectomy be aborted or is there a place for palliative resection? Methods Between 2002 and 2015, 681 patients with potentially resectable esophageal cancer were sheduled for neoadjuvant therapy and subsequent esophagectomy. In 552 patients, a potentially curative esophagectomy was performed. In 12 patients, unexpected disease was discovered during surgery but esophagectomy was performed with synchronous resection of metastases; 10 of them had oligometastatic disease (≤4 single-organ metastases). Esophagectomy was not performed in 117 patients (because of disease progression in 50); 14 were also single-organ oligometastatic. Data of 10 single-organ oligometastatic patients who underwent esophageal resection (group 1) were compared those of 10 non-resected but treated counterparts (group 2) and with 228 patients who underwent potentially curative esophagectomy with persistent pathological lymph nodes (group 3). Results Five oligometastatic esophagectomy patients had lung metastases: 1 peritoneal, 2 adrenal, 1 pleural, and 1 pancreatic. Two oligometastatic non-resected patients had lung, 5 liver, and 3 brain metastases. Median overall survival was 21.4, 12.1, and 20.2 months in the respective groups (group 1 vs. group 2  p = 0.042; group 2 vs. group 3  p = 0.002; group 1 vs. group 3  p = 0.88). Conclusions Survival is longer in patients undergoing palliative esophagectomy with unexpected single-organ oligometastatic disease and comparable to survival in patients with persistent pathological lymph nodes. Palliative resection in these patients seems to be justified.

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