The growing role of precision and personalized medicine for cancer treatment

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Abstract

Cancer is a devastating disease that takes the lives of hundreds of thousands of people every year. Due to disease heterogeneity, standard treatments, such as chemotherapy or radiation, are effective in only a subset of the patient population. Tumors can have different underlying genetic causes and may express different proteins in one patient versus another. This inherent variability of cancer lends itself to the growing field of precision and personalized medicine (PPM). There are many ongoing efforts to acquire PPM data in order to characterize molecular differences between tumors. Some PPM products are already available to link these differences to an effective drug. It is clear that PPM cancer treatments can result in immense patient benefits, and companies and regulatory agencies have begun to recognize this. However, broader changes to the healthcare and insurance systems must be addressed if PPM is to become part of standard cancer care.

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Most cited references 160

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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

F. Stephen Hodi, Steven J O'Day, David F McDermott … (2010)

An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)

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Julie Brahmer, Karen L. Reckamp, Paul Baas … (2015)

New England Journal of Medicine, 373(2), 123-135

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Molecular portraits of human breast tumours.

Charles Perou, Therese Sørlie, Michael B. Eisen … (2000)

Human breast tumours are diverse in their natural history and in their responsiveness to treatments. Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each cell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the level of expression of every gene in the genome. Here we have characterized variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a distinctive molecular portrait of each tumour. Twenty of the tumours were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumour samples from the same individual were almost always more similar to each other than either was to any other sample. Sets of co-expressed genes were identified for which variation in messenger RNA levels could be related to specific features of physiological variation. The tumours could be classified into subtypes distinguished by pervasive differences in their gene expression patterns.

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Author and article information

Journal

Journal ID (nlm-journal-id): 101622420

Journal ID (pubmed-jr-id): 42351

Journal ID (nlm-ta): Technology (Singap World Sci)

Journal ID (iso-abbrev): Technology (Singap World Sci)

Title: Technology

ISSN (Print): 2339-5478

Publication date Nihms-submitted: 23 January 2019

Publication date (Electronic): 11 January 2019

Publication date (Print): Sep-Dec 2018

Publication date PMC-release: 30 January 2019

Volume: 6

Issue: 3-4

Pages: 79-100

Affiliations

[1 ]Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, USA.

[2 ]Department of Chemical & Biochemical Engineering, Rutgers University, 98 Brett Road, Piscataway, NJ 08854, USA.

Author notes

Author contributions were as follows: Krzyszczyk played a leading role in the organization, flow, project management, and final submission of the article. White also played a leading role when setting the initial foundation of the review. Acevedo helped with organization during final submission. Davidoff and Krzyszczyk worked together to envision and create all figures. The written contributions are as follows: for the Introduction: Timmins, Davidoff, and Krzyszczyk; for Acquiring PPM Data: Acevedo, Davidoff, Hartmanshenn, Patel, and Krzyszczyk; for Developing a PPM Product: Timmins, Marrero-Berríos, Acevedo, Sherba, Patel, Balter, Davidoff, and Fritz; for Broader Consequences of PPM: White, Lowe, O’Neill, and Timmins; for Outlook: O’Neill and Timmins; and for Summary and Conclusions: Krzyszczyk.

Schloss played an essential role in the development of the review article, from beginning to end. Her support and feedback greatly contributed to the completion of a polished, final product. As scientific leaders, Androulakis and Yarmush provided knowledgeable perspectives and opinions on the field of PPM. Yarmush also played an important role in the original conception and in guiding the group of authors during the evolution of the article.

Correspondence should be addressed to: M.Y. ( yarmush@ 123456soe.rutgers.edu )

Article

Manuscript ID: NIHMS1007676

DOI: 10.1142/S2339547818300020

PMC ID: 6352312

PubMed ID: 30713991

SO-VID: 3327793b-9a83-4cf4-8235-fc6f4371f593

License:

This is an Open Access article published by World Scientific Publishing Company. It is distributed under the terms of the Creative Commons Attribution 4.0 (CC-BY) License. Further distribution of this work is permitted, provided the original work is properly cited.