Editorial [Hot Topic: Mechanisms of Drug Sensitivity and Resistance in Cancer (Guest Editor: Lorraine O'Driscoll)]

It was with great pleasure that I accepted the invitation to be Guest Editor for this issue of Current Cancer Drug Targets. This volume collates reviews by experts on a wide range of research topics relevant to anti-cancer drug sensitivity and resistance, considering both traditional chemotherapeutic agents and newer, targeted therapies. The use of chemotherapy to treat cancer began in 1943 following the observation of leukopenia in those exposed to mustard gas (alkylating agent) after the explosion of a battle ship in Bari harbour during World War II. This alkylating agent was adapted for i.v. application and it produced dramatic, if short-lived, responses in lymphoma and leukaemia patients. Advancing on this, an extensive range of anti-cancer chemotherapeutic agents have been developed and are used in the oncology clinic. Such anti-cancer drugs aim to destroy cancer cells by stopping them from growing or multiplying. Unfortunately, due to the relative non-specific effects of some of these drugs, healthy cells (especially those that divide quickly) can also be harmed, resulting in undesirable side-effects. Based on our increasing understanding of normal versus cancer cells, in recent years the specific design and targeting of anti-cancer treatment is becoming increasingly sophisticated. The initially crude chemotherapy poisons which have since been continuously fine-tuned to increase efficacy and reduce side-effects and the newer “targeted agents” (which more specifically target features of cancer cells, with more limited side-effects) are set to revolutionise cancer treatment. Most types of cancer show some response to traditional chemotherapy and/or newer targeted agents, but only a limited number of forms of cancer can be completely cured by these approaches. In fact, the successful treatment of cancers varies greatly depending upon the specific malignancy. Some cancers, such as testicular seminoma, leukaemias and malignant lymphomas, are highly responsive to anti-cancer treatment; others are devastating diseases, showing limited, if any, response to currently available therapies. Unfortunately, intrinsic and acquired resistance to anti-cancer agents still represents a serious obstacle to success as patients refractory to treatment often exhibit resistance to multiple anti-cancer agents of differing structures and, often, differing functions. This clinical resistance, comparable to the experimental phenomenon termed multiple drug resistance (MDR), is likely to be multifactorial and heterogeneous, with many molecular mechanisms potentially contributing to the drug resistance phenotype. This resistance -whether inherent or acquired- of cancer cells to the effects of such agents is a serious problem, which we need to better understand and overcome. Studies on mechanisms of cancer drug resistance have yielded, and continue to yield, important information about how to circumvent this problem to improve response. Applying both basic and advanced analytical technologies, genome-wide studies correlating drug response phenotypes with large DNA, RNA, and miRNA microarray and proteomic datasets are being performed to identify the genes, RNAs, and proteins involved in drug sensitivity or resistance. The goal is to identify panels of sensitive- and/or resistance-associated genes, that are predictive of treatment response, for each anti-cancer agent/treatment regime. The hope is that such emerging panels of biomarkers will offer the potential for the selection of optimal treatment regimens for individual patients and also for the identification of novel therapeutic targets to overcome drug resistance.