**13. Conclusion**

vaccine against MDR/XDR-TB and revealed that agglutinating virus of Japan/Heat-Shock-Protein65DNA+Interleukin-12-12DNA vaccine provided strong therapeutic efficacy in killing MDR/XDR-TB bacilli in mice and monkey models [73]. A recent experiment using MDR-TB monkey models which received normal and genetically altered Bacilli Calmette Gue′rin (BCG) vaccines demonstrated that these 2 groups of monkeys survived well compared to the control group [74]. Another study in XDR-TB mice model showed ability of interleukin-7 to kill the

Totally drug-resistant tuberculosis (TDR-TB or XXDR-TB) was recently defined as TB bacilli which resist to all first-line and the 6 second-line drugs (para-aminosalicylic acid, fluoroqui‐ nolones, aminoglycosides, thiamines, polypeptides, and cycloserine) [75]. Meanwhile, a recent report from the US-CDC listed 7 challenges that should be addressed before new terminology

**1.** The definition should not hinge on resistance to all drugs tested, because the number of

**2.** In vitro testing data suggest cross-resistance among different drugs within a class of drugs or closely related classes of drugs (e.g., polypeptides and aminoglycosides) is not 100%.

**3.** Research and reference laboratories in many countries do not test for resistance to the third-line drugs (linezolid, thioridazine, other phenothiazines, monobactams (merope‐ nem, imipenem), macrolides, metronidazole and other imidazoles, clofazimine, and

**4.** DST for several anti-TB drugs is not sufficiently reliable or reproducible; retesting the

**5.** There are several new anti-TB agents in development pipeline that will be prototypes for new classes of antimycobacterial drugs or add new chemical entities to existing class. **6.** Avoiding the unintended implication that patients with TDR-TB should not or cannot be

**7.** Global laboratory capacity for DST of *Mycobacterium tuberculosis* isolates remains limited [75]. Two cases of TDR-TB with controversies of terminology and treatment occurred in 2003 in Italy and firstly reported in 2007 [77]. Currently, in Thailand, patients with all anti-TB drug-resistance will be prescribed isoniazid alone for lifelong whereas no standardized treatment is recommended yet. During 21-22 March 2012, the WHO had convened a technical consultation to discuss the feasibility and implications of a definition to cover more advanced patterns of TB resistance than XDR-TB [78]. The WHO concluded that reports of severe patterns of anti-TB drug resistance ( worse than XDR-TB alone) are increasing whereas a new definition of anti-TB drug resistance beyond XDR-TB is not recommended [78]. This undefined resistance patterns contributed to technical difficulties

of TDR-TB should be considered for adopting [76], following are the challenges:

bacilli [74].

**12. Totally drug-resistant tuberculosis**

256 Tuberculosis - Current Issues in Diagnosis and Management

drugs tested varies widely between laboratories.

same isolate provides a different result in many cases.

amoxicillin/clavulanic acid).

treated.

As countries are purchasing and using second-line drugs, the likelihood of misuse and developing of TB-resistant strains increases. Currently, WHO and its partners have reached the phase of expanding MDR-TB control as a component of a comprehensive TB control programme. Launching in 2002, the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) expected that requests for second-line drugs for MDR-TB management should go through the Green Light Committee to prevent their misuse. The number of Green Light Committee-approved MDR-TB control programme is increasing rapidly as a result of main streaming of MDR-TB management into general TB control efforts. Expanding projects and accelerating evidence gathering are essential to further develop international policies. The TBendemic countries themselves and the ability of the technical agencies, as well as the donor community are the factors of future success to expand MDR-TB control programmes.


**6. Education**

Many real time remote –based laboratory models have been constructed to help the students in schools and higher education institutions to perform the research and gain the knowledge from their own location itself. Several laboratories including the light sensing experiment designed by Singh et al. [14] using LabVIEW, LDR and LM35 sensor, the phasor estimation algorithm using NI ELVIS kit designed by Mondal et al. [15], operational process monitoring application using SHRIMP VL application, analog electronics experiment using "RedPitaya" [16] etc. The LabVIEW has been effectively and efficiently included in many studies in literature to enhance and boost the research community. Polat et al. [17], designed the Distance Vocation Education and Traning D-VET to monitor the lighting levels of LED lamps in remote laboratory with the help of PID controller, Sensor, Actuator, NI-IMAQ software and CompactRIO DAQ.

Azenova et al. [18] designed an e-learning course for second year industrial students under the category of laboratory experiments in electronics. The LabVIEW is incorporated in the Goodyear e-learning model they have adopted for implementing to their students. The basic laboratory experiments like clipper, clamper, inverting and non-inverting amplifier, summing and differential amplifier were simulated with the help of virtual instruments front panel in LabVIEW.

## **7. Miscellaneous applications**

The fault detection in analog circuit can be easily analyzed with the help of LabVIEW interfaces using deep forest learning method. Zhen et al. [19] have designed the fault diagnosis scheme with the Waveform generator Agilent 33250, Data acquisition module NI 1042q, LabVIEW, Digital oscilloscope Agilent 54853 along with power supply and testing circuit. The outputs of testing circuit are collected by data acquisition module and stored in the LabVIEW and used for further diagnosis.

For assessing the quality of water to ensure the living of aquatic species like fishes in a healthy environment. Othman et al. [20], proposed a system using the sensors to measure the pH level and temperature of the water in the tank. The data

**123**

**Author details**

**8. Conclusion**

*Certain Applications of LabVIEW in the Field of Electronics and Communication*

collected from the sensors are given to the Data Acquisition System (DAQ ) NI myRIO-1900. Then the data will be analyzed periodically in the workstation to ensure the safety of aquatic animals. The interface between DAQ and workstation is created with the help of LabVIEW software. The temperature and pH measure-

Ahmed et al. [21] discussed the implementation of LabVIEW software to control the FESTO MPS PA compact workstations as part of remote laboratory. In the paper they designed the Easyport USB data acquisition card based on activeX elements to interface with LabVIEW and control the applications in Fluid Lab. To obtain the real time information from the Sensors and actuators of MPS-PA station various VI were included. To incorporate remote monitoring web server of LabVIEW is required. With the help of the VI the user can adjust the parameters of Controller and with help of IP camera and web server the MPS PA compact workstation can be monitored remotely. Proportional-Integral-Derivative (PID) and ON/OFF controllers these two experiments as part of laboratory course were implemented using the

Mikhoylov et al. [22] aimed to monitor the specific content from the broadcast channels using the help of Cognitive Radio (CR). For the real time data analytics, particular subset of channels from the selective frequency range will be chosen and the significant information in the subset will be relayed for monitoring in the remotely using the VI from LabVIEW. For monitoring Software Defined Radio (SDR) technology USRP 2900/2901 and LabVIEW were utilized in the design. The key factor in the application is to either receive & process or transmit the subset of signals in the

digitized format with the help of the packages available in the LabVIEW.

The applications of LabVIEW in electronics and communication field has been presented in this chapter. The role of LabVIEW in Speech signal processing, Photovoltaic cell emulator, Fault diagnosis scheme, Cognitive radio signal analysis, FESTO workstation control, Water tank surveillance, Embedded system like the Crude Oil Separator, smart turf harvesting machine and robotics applications were discussed briefly. The demonstration and exploration of laboratory courses for school and college students are in reach of hand because of the interface provided

Prema Ramasamy\*, Shri Tharanyaa Jothimani Palanivelu and Abin Sathesan

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Bannari Amman Institute of Technology, Erode, Tamil Nadu, India

\*Address all correspondence to<EMAIL_ADDRESS>
provided the original work is properly cited.

by the LabVIEW and source of the Internet.

*DOI: http://dx.doi.org/10.5772/intechopen.96301*

system designed by Ahmed et al.

ments are displayed in the front panel of LabVIEW.

#### *Certain Applications of LabVIEW in the Field of Electronics and Communication DOI: http://dx.doi.org/10.5772/intechopen.96301*

collected from the sensors are given to the Data Acquisition System (DAQ ) NI myRIO-1900. Then the data will be analyzed periodically in the workstation to ensure the safety of aquatic animals. The interface between DAQ and workstation is created with the help of LabVIEW software. The temperature and pH measurements are displayed in the front panel of LabVIEW.

Ahmed et al. [21] discussed the implementation of LabVIEW software to control the FESTO MPS PA compact workstations as part of remote laboratory. In the paper they designed the Easyport USB data acquisition card based on activeX elements to interface with LabVIEW and control the applications in Fluid Lab. To obtain the real time information from the Sensors and actuators of MPS-PA station various VI were included. To incorporate remote monitoring web server of LabVIEW is required. With the help of the VI the user can adjust the parameters of Controller and with help of IP camera and web server the MPS PA compact workstation can be monitored remotely. Proportional-Integral-Derivative (PID) and ON/OFF controllers these two experiments as part of laboratory course were implemented using the system designed by Ahmed et al.

Mikhoylov et al. [22] aimed to monitor the specific content from the broadcast channels using the help of Cognitive Radio (CR). For the real time data analytics, particular subset of channels from the selective frequency range will be chosen and the significant information in the subset will be relayed for monitoring in the remotely using the VI from LabVIEW. For monitoring Software Defined Radio (SDR) technology USRP 2900/2901 and LabVIEW were utilized in the design. The key factor in the application is to either receive & process or transmit the subset of signals in the digitized format with the help of the packages available in the LabVIEW.


**3.1 Experimental environment**

In order to support this model-driven domain ontology modelling approach, Borland Together (Borland, 2006), a famous MDA tool, is employed in our experiment. By using UML extension mechanism, we implemented the UML Profile for RDF and OWL in Borland Together. In addition, Borland Together tool enable the model-to-model transformation, and this facilitates the transformation from PIM to PSM. Through the developed model-to-code transformation engine, we realize the transformation from PSM to ontology file encoded by OWL. At last, in order to verify whether the transformation is correct or not, the generated OWL file is imported in Protégé tool to test. By the experimental verification, the proposed model-driven ontology modelling approach can nicely support the constructing methodology of telecommunications service domain ontology.

Under the guidance of this approach, our research team has created a telecommunications service domain ontology knowledge repository which consists of around 430 telecommunications services-related ontology concepts/terminologies and 245 properties. Currently, these ontologies are published on our website (BUPT, 2009), see Figure 21.

description model triples (C, R, G). The states, input events and transformation function of the automaton correspond to the class nodes, relation nodes and relation matrix set respectively in PSM class graph. The begin state of automaton is the owlClass node or objectProperty/datatypeProperty node in class nodes and the terminate states set includes all class nodes whose out-degree are zero and all nodes have been transformed by the

The model transformation regulation table defines the transformation regulation from UML Profile for RDF and OWL to OWL language. In the states jump process of model transformation automaton, corresponding regulation is used to perform model transformation. In the process of formulating the transformation regulation, the relations between every label node should be unified, which makes the regulation can be formulated depending on the OWL label structure and the relations between UML model elements.

Model output module only stores the formalized result of the transformation to the appointed path. And in order to verify the validity of the OWL file transformed, user can import the generate code into protégé tool for verification. Protégé is an ontology editor developed by Stanford University, which represents the OWL structure in graphic interface

By using the above mentioned model to code transformation approach, the PSM of Figure

In this section, we describe our experimental environment, the implemented service use case and present the obtained evaluation results to validate the semantic interoperability enabled

In order to support this model-driven domain ontology modelling approach, Borland Together (Borland, 2006), a famous MDA tool, is employed in our experiment. By using UML extension mechanism, we implemented the UML Profile for RDF and OWL in Borland Together. In addition, Borland Together tool enable the model-to-model transformation, and this facilitates the transformation from PIM to PSM. Through the developed model-to-code transformation engine, we realize the transformation from PSM to ontology file encoded by OWL. At last, in order to verify whether the transformation is correct or not, the generated OWL file is imported in Protégé tool to test. By the experimental verification, the proposed model-driven ontology modelling approach can nicely support the constructing

Under the guidance of this approach, our research team has created a telecommunications service domain ontology knowledge repository which consists of around 430 telecommunications services-related ontology concepts/terminologies and 245 properties.

Currently, these ontologies are published on our website (BUPT, 2009), see Figure 21.

and makes the verification of OWL code validity more quickly and conveniently.

18 is transformed into the corresponding ontology encoded by OWL like Figure 20.

**3. Experimental environment, use cases and evaluation**

methodology of telecommunications service domain ontology.

And good regulation is easy to extend in the future.

by telecommunications service domain ontology.

**3.1 Experimental environment**

*<IP_ADDRESS>.4 Model output module*

automaton.

Fig. 20. A part of formal network ontology encoded by OWL.

Telecommunications Service Domain Ontology:

**3.3 Lessons learned**

using URIs and RDF.

service integration.

**4. Conclusion**

representations of telecommunication and Internet services.

Semantic Interoperation Foundation of Intelligent Integrated Services 207

Based on this domain ontology, we described the telecom network capability services in the semantic level to validate its feasibility. We apply the semantic web service and ontology technologies to the telecommunications service domain, and present an infrastructure to enable the semantic interoperability of telecom network and Internet in the service layer (Qiao et al., 2008b). The proposed approach improves the accuracy of telecommunication network services description, discovery and matching, and unifies the semantic

Currently, under the shift trend from Web2.0 to Web3.0 era, there have been some initial semantic web applications in Internet field. For example, the system of Twitter allows tweets to be tagged with information that will not appear in the message but can be read by computers (Twitter, 2010). Google is using structured data open standards such as microformats and RDFa to power the rich snippets feature. It's an experimental Semantic Web feature (Google, 2010). FOAF (Friend of a Friend) (FOAF, 2010) is a machine-readable ontology describing persons, their activities and their relations to other people and objects. As a "practical experiment" in the application of RDF and Semantic Web technologies to social networking, FOAF is becoming more and more popular now (FOAF, 2000). In addition, Linked Data (Linked Data, 2007) is a recommended best practice for exposing, sharing, and connecting pieces of data, information, and knowledge on the Semantic Web

However, the semantic web applications in telecommunication services domain are still in an early research phase. Although RDF-based CC/PP (Composite Capability/Preference Profiles) (W3C, 2007) and UAProf (User Agent Profile) (OMA, 2001) are used to describe the terminal capability and user preference, other practical applications are very rare. Therefore, in order to eliminate the semantic gap between telecom network and Internet, the research on semantic web applications in telecommunications field still need to be further enhanced. Telecommunications service domain ontologies consist of various domain related concepts and knowledge, which is the base of semantic interoperability. The wide acceptance of standards and common practices of telecommunications service domain ontologies are still a way ahead. The promotion of the telecommunications service domain ontology by related standardization organizations would be in the foundation for the semantic interoperability of heterogeneous communications equipments and the industrial practical convergent

The network heterogeneity and service convergence are the main characteristics of future network. The provision of self-adaptive intelligent integrated services has become the pursuing goal of network carriers and value-added service providers. Dynamic discovery and composition of services are the important enabling technologies for self-adaptive integrated services. In the service discovery and composition process, semantic interoperability is a key issue. Actually, ontology, as a semantic interoperability and knowledge sharing foundation, has obtained more and more attentions. However, telecommunication service field consists of a large number of concepts/terminologies and

Fig. 21. The published telecommunications service domain ontology.

#### **3.2 Use cases: Semantic telecommunications network capability services**

In order to support the shift from traditional closed business model to open service ecosystem of telecom industry, NGN (Next Generation Network) and 3G network all adopt the open API (Application Programming Interface) technologies in the service layer, such as Parlay/OSA and Parlay X (Moerdijk & Klostermann, 2003). Thus, the telecommunication network services, such as call control, short messaging service, and location service, are available to the service developers in the form of APIs. This facilitates the value-added service development. With the development of distributed computing technology, Service-Oriented Architecture (SOA) is also imported into the telecommunications service domain by Parlay Web Service specifications. However, the open interface specifications of telecommunication networks are currently still in the syntactic level. As WSDL (Web Services Description Language)-based telecommunication network services lack the rich semantic annotation information, the keyword-based service matching cannot enable an accurate service discovery. So, currently value-added services often directly invoke the needed telecom network services provided by a specific network carrier. This results in the tight-coupling of application logic and service resources, which limits the provision of dynamically self-adaptive services. The applications cannot dynamically discover satisfied telecom network services and compose them according to the context environment. Facing the heterogeneous networks and personalized user demands, the self-adaptation has become a very important feature of future intelligent integrated service. Therefore, the semantic interoperability of telecom network and Internet in the service layer should be considered.

Based on this domain ontology, we described the telecom network capability services in the semantic level to validate its feasibility. We apply the semantic web service and ontology technologies to the telecommunications service domain, and present an infrastructure to enable the semantic interoperability of telecom network and Internet in the service layer (Qiao et al., 2008b). The proposed approach improves the accuracy of telecommunication network services description, discovery and matching, and unifies the semantic representations of telecommunication and Internet services.


**4. Effects of nitrate, ammonium, urea, and glutamine on nodule growth and nitrogen fixation activity**

In addition to the inhibitory effect of nitrate on nodule growth and nitrogenase activity, the repressive effect of ammonium is also reported [14], whereas urea did not reduce nodule dry weight and nitrogen fixation activity in hydroponically grown soybean [17, 18]. The difference in inhibitory effects by the forms of N compounds is not fully understood yet. Yamashita et al. [23] investigated the effect of various forms of nitrogen; nitrate, ammonium, urea, and glutamine on the quick and reversible inhibition of nodule growth and nitrogen fixation activity of soybean plants.

Soybean plants were cultivated in a nitrogen-free nutrient solution in a glass bottle, and nitrate, ammonium, glutamine, or urea (1 mM-N) were supplied from 12 days after planting (DAP) to 17 DAP. The increase in individual nodule growth expressed by nodule volume (mm3 ) was shown in **Figure 10**. The inhibitory effects on the nodule growth were severe in nitrate and ammonium treatments, and those by urea and glutamine were smaller than in nitrate and ammonium. On 17 DAP, the increase in nodule dry volume was low in nitrate and ammonium medium in urea and glutamine compared with the control with N-free solution. After N-based solutions were replaced by N-free solutions from 17 DAP to 24 DAP, the nodule growth in all treatments showed the recoveries. These results indicated that the rapid and reversible inhibition is not only by nitrate but also by ammonium, urea, and glutamine. **Figure 11A** shows the dry weight of nodules per plant on 17 DAP. The application of

### **Figure 10.**

*Changes in nodule volume from 12 to 24 DAP for treatments with control (N-free), nitrate, ammonium, urea, or glutamine from 12 to 17 DAP, thereafter cultivated with a N-free culture solution (Experiment 2). Shaded background indicates N treatment period, and white background indicates cultivation with N-free medium. Average and standard error are shown (n = 5). From Yamashita et al. [23].*

### **Figure 11.**

*Comparison of the dry weight of nodules at 17 DAP (A) and at 24 DAP (B), and acetylene reduction activity per plant (C), and specific acetylene reduction activity per nodule g dry weight (D) on 17 DAP of soybean plants supplied with control (N-free), nitrate, ammonium, urea, or glutamine from 12 to 17 DAP, followed by supplying N-free solution from 17 DAP to 24 DAP. Averages and standard errors are shown (n = 4). Different letters above the column indicate significant differences at <0.05 by Tukey's test. From Yamashita et al. [23].*

1 mM-N of nitrate, ammonium, urea, and glutamine for 5 days depressed the nodule weight to 45, 75, 76, and 65% of the control nodules on 17 DAP. After N-free solution was supplied for 6 days following 5-day N treatment, the nodule dry weight on 24 DAP increased in all N treatments similar to the control plants (**Figure 11B**). **Figure 11C** shows the ARA per a single plant, and the activities were depressed in nitrate, ammonium, urea, and glutamine treatment like the decrease in the nodule dry weight (**Figure 11A**). The specific ARA per g DW of nodules on 17DAP were almost the same (**Figure 11D**), so the decrease in ARA per plant is due to lower nodule dry weight and not by a decline in the specific ARA. In this experiment, the DW and N concentrations of roots, stems, and leaves increased after 5 days of N application on 24 DAP compared with the control plants supplied with N-free solution.

15N-labeled 1 mM-N nitrate, ammonium, urea, or glutamine was supplied for 3 days from 21 to 24 DAP, in which the solutions were renewed every day. The whole shoot was enclosed in a plastic bag on 23 DAP, and 13CO2 was exposed to the plants for 1 h. Then the plants supplied with 15N and 13C were harvested on 24 DAP, 26 h after 13CO2 exposure. The labeling of 15N and 13C in each organ was determined by Mass spectrometry. The amount of 15N in nodules (**Figure 12A**) was 0.14 mg from nitrate-15N, 0.26 mg from ammonium-15N, 0.14 mg from urea-15N, and 0.29 mg from glutamine-15N. It is interesting to note that the amount of 15N in nodules is not related to the decrease in nodule DW (**Figure 11A**) and ARA (**Figure 11C**). **Figure 12B** shows the amount of 13C in nodules, and it was 85 mg in control, 27 mg in nitrate, 34 mg in ammonium, 54 mg in urea, and 34 mg in glutamine treatment. The decrease in the amount of 13C in nodules was similar

*Effects of Application of Various forms of Nitrogen on the Growth of Soybean Nodules and Roots… DOI: http://dx.doi.org/10.5772/intechopen.105348*

### **Figure 12.**

*(A) Amounts of N derived from 15N-labeled source in each tissue of soybean plants on 15 DAP supplied for 3 days from 21 to 24 DAP. (B) amounts of C derived from 13C-labeled CO2 in each tissue of soybean plants on 24 DAP supplied for 1 hour at 23 DAP. From Yamashita et al. [23].*

### **Figure 13.**

*Free amino acid concentrations in each tissue of soybean plants on 24 DAP supplied with various N compounds from 21 to 24 DAP. From Yamashita et al. [23].*

to the nodule DW (**Figure 11A**) and ARA (**Figure 11C**) among treatments. This result supports the hypothesis that the depression of nodule growth and nitrogen fixation activity is related to the decline in photoassimilates partitioning but not N supply.

Changes in the free amino acid concentrations in nodules, roots, stems, and leaves were shown in **Figure 13**. The nitrate treatment significantly increased the concentration of the amino acids, especially Asp, Asn, and Glu in the nodules.

The application of ammonia, urea, or glutamine also increased the concentrations of Asp and Asn in nodules compared with control plants although the increases were not higher than nitrate treatment. On the other hand, the amino acid concentrations in the roots show that ammonium treatment remarkably increased the Asn and Asp concentrations, the urea and glutamine treatments also increased the Asn concentration in the roots, but the increase in Asn in the roots treated with nitrate was relatively low. The increase in the Asn and Asp concentrations was the highest in the stems of plants supplied with urea, followed by glutamine, ammonium, and nitrate treatments. The increase in Asn and Asp was observed from nitrate, ammonium, urea, and glutamine treatments.

**Figure 14A** shows the effects of nitrogen compounds on total root length on 34 DAP after long-term nitrogen treatment for 2 weeks. The application of nitrate promoted the total root length by over 2-fold compared with the control plants. On the other hand, the application of ammonium inhibited the root length by only a half of the control. The application of urea and glutamine slightly increased the total root length. Similar trends were observed for the root dry weight (**Figure 14B**). **Figure 14C** and **D** show the increase in primary root and lateral roots for the first week of N application from 20 to 27 DAP, and the second week from 27 to 34 DAP. By NO3 − application, the growth of the lateral roots was promoted, but the primary root was not. On the other hand, the inhibitory effects of NH4 + were evident both for the

### **Figure 14.**

*Total root length (A) and the dry weight of roots (B) on 34 DAP after two weeks of the treatments with various forms of N compounds, and the increase in the primary root length (C), and lateral root length (D) for the first week (blue bar) and the second week (red bar). (A) Total root length, (B) Root dry weight, (C) Increase in primary root length, and (D) Increase in lateral root length. From Yamashita et al. [23].*

*Effects of Application of Various forms of Nitrogen on the Growth of Soybean Nodules and Roots… DOI: http://dx.doi.org/10.5772/intechopen.105348*

primary root and the lateral roots. The promotive effects on the length of the primary root and not on the lateral root length were observed by urea and glutamine applications like nitrate.


**1. Introduction**

To this date, management of heavily pretreated patients with metastatic colorectal cancer, who present with good performance status and adequate organ function reserve, constituted a challenge for oncologists. However, two anticancer therapies dedicated for this specific group of patients became available nowadays. One of them is regorafenib, an oral inhibitor of protein kinases associated with angiogenesis. Another one is trifluridine/tipiracil (TAS-102), an orally administered combination of a thymidine-based nucleic acid analog, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor. Treatment with both anticancer agents contributed to a significant improvement of overall survival (OS) and progressionfree survival (PFS) in randomized III phase studies of Caucasian (CORRECT and TERRA) and Asian patients (CONCUR and RECOURSE). Recently, clinical benefits associated with administration of both drugs and good tolerability thereof were also confirmed in an observational study, REGOTAS. The aim of currently ongoing trials is to evaluate the efficacy and safety of regorafenib and TAS-102 combined with other anticancer drugs in metastatic colorectal cancer patients. While preliminary results of some of those studies seem promising, more evidence is needed to formulate any clinically relevant conclusions.

Another treatment option in metastatic colorectal cancer is re-induction of previously used chemotherapy with oxaliplatin- or irinotecan-based regimens.

## *Multidisciplinary Approach for Colorectal Cancer*

Importantly, the time elapsed since completion of the primary treatment to the re-induction should not be shorter than 9 months. Finally, patients with metastatic colorectal cancer can receive chemotherapy with mitomycin C plus capecitabine. This generally neglected treatment option seems particularly reasonable in the case of countries in which regorafenib and trifluridine/tipiracil have been registered but are not reimbursed.

The aim of this review paper is to discuss the therapeutic options that could be used in metastatic colorectal cancer patients after three or more lines of systemic therapy.