Current best practices and rationalistic perspectives in causation-based prevention, early detection and multidisciplinary treatment of breast and gastric cancer

Gastric & Breast Cancer e-journal
DOI: 10.2122/gbc.2017.0267


Linear transcription dogma: the standard approach for drug discovery.

William CS CHO, MD, PhD.

Affiliation: William CS Cho, Scientific Officer, Department of Clinical Oncology, Queen Elizabeth Hospital, Room 1305, 13/F, Block R, 30 Gascoigne Road, Kowloon, Hong Kong.


Targeted drugs alone or added to chemotherapy represent the grand hope of systemic therapy to kill deregulated cancer cells, micro-metastases, and distant metastases. However, despite the progress over the past decades with more than 80 targeted drugs approved by the FDA, there are two major limitations. First, their temporary efficacy with subsequent timeline dissemination of resistant cancer cells leading to patient’s death, and second their moderate efficacy in modern oncological chemotherapeutics which explains the high resistance rates.
Despite these limitations, pharmaceutical industry continues to major investments in linear transcription drugs to the development of novel targeted drugs. This conventional strategy since Crick’s dogma in 1958 which is in contrast to recent non-linear transcription one revealed recently by the ENCODE project, can be justified by the high financial benefits derived by approval of new very expensive targeted drugs.
This Review describes the rapid progress and approval of new drugs by the FDA that are documented by the discovery of novel therapeutic targets with Next-Generation Sequencing (NGS) techniques. Advances in overcoming the unmet needs of       primary and acquired resistance by using Whole Exome Sequencing (WES), Whole Genome Sequencing (WGS), and RNA Sequencing (RNA-seq) for the identification of new druggable mutations and drugs targeting these variants are discussed.


(Citation: Gastric & Breast Cancer 2017; 12(2): 122-134)



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last update: 31 August 2017