Review: biomarkers towards personalised therapy in cancer
Since the sequence of the human genome was published some 20 years ago, omics strategies have enabled the generation of detailed molecular signatures of cancers and their subtypes.
This new information has spurred efforts towards stratification of patients bearing those signatures, development of targeted therapies, and has opened up the paradigm of precision medicine – by using biomarkers. However, the inherent complexity and ever-shifting genetic landscape of cancer has seen many targeted therapies become provocateurs of treatment-induced phenotypes and acquired resistance. Even promising biomarkers that have been identified in attempts to bypass this harbour issues concerning translation and implication into the clinic. Yet there is hope. Evidence from the successful use of biomarkers for diagnosis, screening and management of cancers such as breast and prostate has resulted in earlier diagnoses, higher survival and lower morbidity rates, thus validating the clinical relevance of this concept. Additionally, research into new biomarkers such as PD-1 and CTLA4, and new biomarker classes such as microRNAs and exosomes, coupled with the promise of stronger connections between the realms of molecular biology and biotechnology, means that the new era of biomarker discovery for precision medicine in cancer begins now.
Cancer has existed for millennia, and efforts to fight it have been met with galling failures. We have come a long way from Sidney Farber’s attempts to cure leukaemia by administering folic acid mimics. Following the sequencing of the human genome and development of high-throughput sequencing techniques, the number of genetic signatures illustrative of cancer subtypes has soared. However, in spite of these developments mortality has not significantly improved over the past few decades.1,2 The complex nature of treating a genetically multifarious disease with the propensity to develop therapy resistance quickly is reflected in the low approval rate of new drugs. Furthermore, the ethical and human considerations of sending a drug that may at best marginally improve survival through clinical trials are substantial.
While cancer incidence across our ageing population is increasing, treatment still relies heavily on a technique that has existed as long as medicine itself – surgery – and a cache of chemotherapeutics rife with noxious side effects. The targeted therapies that do exist can push development of further genetic/epigenetic irregularities leading to resistance, metastatic propagation and recurrent disease.3,4 Efficient management of this scenario hangs on identifying suitable treatment strategies from the outset, and monitoring treatment response both throughout and after the course of a disease.
Thus, as the prospect of a cancer cure may seem increasingly distant, development of biomarkers to aid in decision making and predict treatment outcome for personalised therapy now represents the Holy Grail of cancer treatment.