Theranostics: A treasured tailor for tomorrow

Abstract

Emerging as a targeted, safe, and efficient pharmacotherapy is the approach of theranostics, which focuses on patient-centered care. It is a combination of diagnosis and therapeutics. It provides a transition from conventional medicine to personalized medicine. It deals with the custom made treatment plan based on uniqueness of every individual thus resulting in right drug for the right patient at the right time. Genetics plays a significant role in theranostics. Theranostics provides a cost-effective specific successful treatment protocol. Pharmacogenetics, proteomics and biomarker profiling forms the backbone of theranostics. The role of theranostics is interestingly appreciated at multi levels with special consideration in oncology wherein nano formulations in the form of liposomes, dendrimers, polymeric nanoparticles, metallic nanoparticles, quantum dots and carbon nanotubes play a very important role. Thus, theranostics is a holistic transition from trial and error medicine to predictive, preventive and personalized medicine leading to improved quality care of pharmacotherapy.

Advances in science have always been an inseparable part of human contribution to the welfare of mankind. Traditional medicine has relied upon rationale history taking, relevant clinical examination for arriving at the cause of the problem – diagnosis and planning of appropriate management initially, which was with herbs, and which later gradually progressed to chemical products of plants and various other sources resulting in diverse medical modalities. The arrival of diagnosis and treatment was a reactive approach, which completely depended upon and focused on the individual patient's clinical signs and symptoms, past medical history, personal history, family history, and results of investigations from laboratory and occasionally imaging to diagnose illnesses and planning the relevant treatment modalities with common platform being medical management with drugs.

Patient-centered care has always been the priority and predominant basis of treating patients with drugs and more important a transition from universal medicine that is, “one medicine fits all” practice to personalized medicine has emerged as a revolution to include the unique approach for custom-made drug therapy based on interpersonal variation in drug response. This has to the exploration of an amazing platform called theranostics, which is an intimate connection of diagnosis and therapeutics that could provide treatment protocols, which are more specific to individuals and therefore, more likely to provide improved prognoses thus drawing diagnosis and therapy closer. The objective is to render safe and more targeted efficient pharmacotherapy by offering individual patients the “right” drug at the “right” dose in the form of theranostics as part of personalized medicine.[1,2,3,4]

Theranostics - portmanteau of therapeutics and diagnostics Portmanteau means a combination of two (or more) words into one new word. Theranostics combines therapy and diagnostics.[5] The pioneer of the term theranostics is attributed to John Funkhouser. The term “theranostics” was coined to explain developments in science to establish more specific and individualized therapies for various pathologies, and to bring about a union of diagnostic and therapeutic applications into a single agent thus leading to a promising therapeutic paradigm involving diagnosis, drug delivery and monitoring of treatment response.[6]

Theranostics is a proposed process of diagnostic therapy for individual patients - to test them for possible reaction to taking a new medication and to tailor a treatment for them based on the test results.

Of utmost importance is that theranostics plays a significant role in economic aspect resulting in cost-effective treatment plans and highly efficient and specific medicine protocols, serving as a guidance in preclinical drug development or clinical trial eligibility to obtain positive results.

Genetic information forms a key part in theranostics and it has been contributed by Human genome project, which emphasizes on variations in genetics and expected risk for many of the common diseases. Interestingly, this has led to the growth of fields such as pharmacogenetics and proteomics.[7]

Pharmacogenetics

Pharmacogenetics is the science that studies about the individual variations in DNA sequences and responses to treatment interventions by biomarker. This genotyping approach helps in tailoring drug therapy with advantages such as reduction in time and cost and increase in success rates. The field of pharmacogenomics extends to cover variations in RNA and proteins also that may have significance in treatment decisions.[8]

Proteomics

It is the science that deals with comprehensive analysis and characterization of all of the proteins and protein isoforms encoded by the human genome. Proteomics also plays a very vital role in tailoring therapy and have therapeutic implications because proteins play an important role in the physiological aspect of the cell when compared to the genes which is the storehouse of information.[9]

Biomarker Profiling

Theranostics tailors optimized therapies based on biomarker profile of each individual patient's specimen reducing side-effects and increasing tissue bio availability thus reducing treatment costs and improving response to treatment. Today's biomarker is tomorrow's theranostics.[10]

Challenges in Theranostics

The fundamental principle of theranostics has been followed since decades, with the utilization of radioiodine to diagnose (image) and manage cancers of thyroid gland which dates back to 1940. Since its inception until date, theranostics has been fostering unremarkable tailored and targeted therapy.

In the context of pharmacotherapy, the fundamental aspect of individual absorption distribution metabolism excretion is to understood with regards to the complex interactions and detailed characterization, especially focusing on the functional variations genetically also including population variations. Furthermore interestingly, epigenetic variations and the impact of environmental factors including the circadian rhythms on an individual's response to drugs needs to be assessed specific to each individual.

Apart from the above variations educating the health care provider, payor, regulator, and the patient also is mandatory. Theranostics has extended impact on patients in that more than individual centric care, guaranteed outcomes expected by patients seem to pose an alarming aspect of theranostics.

Due to existing less targeted and tailored pharmacotherapy, the resulting loss in 40% of ineffective treatment has resulted in loss in overall economy of the pharmacological market accounting to $400 billion out of total global pharmaceutical market $825 billion. Our country accounts to 20% of global population and involves 2% of global pharmaceutical market, especially with respect to generic drugs. Every year after conducting clinical trials, approval by the Central Drugs Standard Control Organization has considerably decreased since 2009.

The most common reason for failure and avoidable deaths, including expensive hospitalization has been found to be side effects associated with less targeted nonspecific therapy contrary to theranostics based management. Furthermore age, and gender, diet, lifestyle of a patient including the intestinal microflora plays a significant role in patient's response to a drug.[11]

Theranostics in Oncology

In contrast to normal cells, cancer cells break the harmony of normal check points and divide and live forever by maintaining their telomeres (a region of repetitive DNA at the end of a chromosome from deterioration thus leading to uncontrolled growth and spread).

Currently, employed techniques in diagnosis are limited by lack of specificity and treatment associated with systemic toxicity. Current treatment techniques for cancer include surgery, radiotherapy, chemotherapy, hyperthermia, immunotherapy, hormone therapy, stem cell therapy, and combinations of above.

Opening new vistas in cancer management in three dimensions – diagnosis treatment and monitoring the response is the application of theranostics, especially with the support of nanotechnology.[12]

Liposomes, dendrimers, polymeric nanoparticles, metallic nanoparticles, quantum dots and carbon nanotubes are examples of nano formulations that can be used as mutifunctional platforms for cancer theranostics. Liposomes are concentric closed bilayer membranes of water insoluble polar lipids that can be used to encapsulate biomolecules and drugs for targeted delivery, while protecting their bioactivity. Members of the fullerene structural class, carbon based are carbon nano tubes. Nano tubes are a sheet of graphite rolled into a cylinder. They are composed of carbon atoms arranged in hexagonal networks that are approximately 1 nm in diameter and 1–100 μm in length. The generation of them takes place by the optical excitation of plasmonic nanoparticles with short pulses of laser. They are used as localized nano bombs to destroy cancer cells. Quantum dots are semi-conductor nano crystals made of cadmium selenide that range from 2 to 10 nm in diameter, which glow when exposed to ultraviolet light and are useful in the detection of cancer in very incipient stages and preferentially killing them. Thus theranostics opens new avenues from point of diagnostic care and allows for holistic patient management approaches.[13,14,15,16,17]

Conclusion

A seamless and interesting integration of multiple imaging and treatment technologies within a single nano particle is required to tackle pathologies. Nanorobots approximately the dimension of bacteria probably 1 day may roam human's bodies tracking out organisms and repairing damaged body tissues.[18]

In the broader sense, theranostics is a proposed diagnostic methodology for personalizing treatment intervention (diagnostic therapy for individual patients).

Theranostics paves a way for the holistic transition from “trial and error” medicine to personalized medicine. Personalized medicine or PM is an interesting field that plans with the customization in caring for health - with relevant medical decisions, rationale practices, and/or various products being tailored to the specific patient.

Contradictory to one decision suits all practice, personalized medicine has revolutionized as a genuine interventional approach for custom-made drug regimen based on variations between patients with respect to drug response rendering increased safety and improved efficiency thus offering the right drug with right dose to the right patient at the right time. This is achieved by properly identifying and appropriately selecting patients with a specific molecular phenotype indicative of positive response to treatment.[19]

Thus, theranostics approach can be considered as “P4 medicine,” that is predictive, preventive, personalized, and participatory. This field promises to increase the quality of clinical care and treatments and will ultimately save costs thus helps to identify the right drug for the right patient at the right time.[20]