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Current Update of Laboratory Molecular Diagnostics Advancement in Management of Colorectal Cancer (CRC)

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Current Update of Laboratory Molecular Diagnostics Advancement in Management of Colorectal Cancer (CRC) diagnostics Review Current Update of Laboratory Molecular Diagnostics Advancement in Management of Colorectal Cancer (CRC) Siew-Wai Pang 1,*, Noel Jacques Awi 1, Subasri Armon 2 , Wendy Wan-Dee Lim 3, John Seng-Hooi Low 3, Kaik-Boo Peh 4, Suat-Cheng Peh 1,3 and Sin-Yeang Teow 1,* 1 Department of Medical Sciences, School of Healthcare and Medical Sciences, Sunway University, Jalan Universiti, Bandar Sunway, Subang Jaya 47500, Malaysia; [email protected] (N.J.A.); [email protected] (S.-C.P.) 2 Pathology Department, Hospital Kuala Lumpur, Jalan Pahang, Kuala Lumpur 50588, Malaysia; [email protected] 3 Sunway Medical Centre, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya 47500, Malaysia; [email protected] (W.W.-D.L.); [email protected] (J.S.-H.L.) 4 Mahkota Medical Centre, Mahkota Melaka, Jalan Merdeka, Melaka 75000, Malaysia; [email protected] * Correspondence: [email protected] (S.-W.P.); [email protected] (S.-Y.T.); Tel.: +60-17-621-6191 (S.-W.P.); +60-37-491-8622 (ext. 7449) (S.-Y.T.) Received: 26 September 2019; Accepted: 23 November 2019; Published: 23 December 2019 Abstract: Colorectal cancer (CRC) continues to be one of the most common cancers globally. The incidence has increased in developing countries in the past few decades, this could be partly attributed to aging populations and unhealthy lifestyles. While the treatment of CRC has seen significant improvement since the advent of target-specific therapies and personalized medicine, CRC is oftentimes detected at late or advanced stages, thereby reducing the efficacy of treatment. Hence, screening for early detection is still the key to combat CRC and to increase overall survival (OS). Considering that the field of medical diagnostics is moving towards molecular diagnostics, CRC can now be effectively screened and diagnosed with high accuracy and sensitivity. Depending on the tumor genotype and genetic profile of the individual, personalized treatments including tyrosine kinase inhibitor therapy and immunotherapy can be administered. Notably, there can be no one single treatment that is effective for all CRC patients due to the variation in tumor genetics, which highlights the importance of molecular diagnostics. This review provides insights on therapeutic modalities, molecular biomarkers, advancement of diagnostic technologies, and current challenges in managing CRC. Keywords: colorectal cancer; molecular; diagnostics; biomarker; technologies; personalized medicine; therapy; genetic; screening; challenges 1. Colorectal Cancer (CRC) and Its Treatment Colorectal cancer (CRC) is one of the most common cancers worldwide, ranking third and second for men and women, respectively. In 2018, Global Cancer Observatory (GLOBOCAN) estimated more than 1.8 million new CRC cases worldwide [1]. There are various therapeutic modalities for CRC depending on the pathological characteristics of the tumor. Laparoscopic surgery is normally carried out for early-stage primary disease, open surgery tumor resection for cases with metastases, and adjuvant radiotherapy for nonresectable cases. Other CRC therapies are neoadjuvant and palliative chemotherapies [2,3], immunotherapy [4], and tyrosine kinase inhibitor (TKI) therapy [5]. The advent of checkpoint inhibitors made of monoclonal antibodies (mAbs) have been a breakthrough for the Diagnostics 2020, 10, 9; doi:10.3390/diagnostics10010009 www.mdpi.com/journal/diagnostics Diagnostics 2019, 9, x FOR PEER REVIEW 2 of 21 Diagnostics 2020, 10, 9 2 of 21 and palliative chemotherapies [2,3], immunotherapy [4], and tyrosine kinase inhibitor (TKI) therapy [5]. The advent of checkpoint inhibitors made of monoclonal antibodies (mAbs) have been a breakthroughtreatment of several for the cancers treatment including of several CRC cancers [6]. The including safety profile CRC and[6]. itsThe effi safetycacy inprofile treating and certain its efficacy CRC inpatient treating populations certain CRC have patient led to multiplepopulations clinical have trials. led to Figure multiple1 summarizes clinical trials. the list Figure of CRC 1 summarizes treatments thereviewed list of CRC according treatments to their reviewed date of applicationaccording to or their approval date of by application the Food and or approval Drug Administration by the Food and(FDA) Drug [7– 17Administration]. Despite advances (FDA) in [7–17]. medical Despite and surgical advances treatment, in medical the long-term and surgical survival treatment, rates have the long-termnot improved survival much rates [18 have]. One not of improved the ways much in which [18]. CRCOne of can the be ways treated in which optimally CRC iscan through be treated the optimallyelucidation is ofthrough individual the elucidation genetic profiles of individual for personalized genetic therapiesprofiles for or precisionpersonalized medicine. therapies Since or precisionCRC has severalmedicine. tumor Since subtypes CRC ha withs several complex tumor mutations subtypes and with genetic complex variations, mutations treatment and decisiongenetic variations,supported bytreatment molecular decision testing supported results can by dramatically molecular improvetesting results the survival can dramatically rate [19]. The improve details andthe survivalspecifications rate [19]. of the The genes details will beand discussed specifications in the nextof the section. genes Withwill be advancement discussed in of DNAthe next sequencing section. Withtechnologies advancement such as of next-generationDNA sequencing sequencing technologies (NGS), such it as is next-generation optimistic that precisionsequencing medicine (NGS), mayit is optimisticbe more accessible that precision and a medicineffordable, may thereby be more improving accessible clinical and outcomes.affordable, The thereby sub-sections improving below clinical will outcomes.discuss the The current sub-sections treatment below methods will fordiscus CRC.s the current treatment methods for CRC. FigureFigure 1. SimplifiedSimplified timeline timeline of of colorectal cancer (CRC (CRC)) treatment options reviewed. The The timeline timeline is is notnot constructed constructed according according to to scale. scale. The The red red boxes boxes on on the the right right represent represent the the type type of of treatment, treatment, where where CTCT == chemotherapy,chemotherapy, SUR SUR == surgery,surgery, IMT IMT == immunoimmunotherapy,therapy, TKI TKI == tyrosinetyrosine kinase kinase inhibitor. inhibitor. 2.2. Molecular Molecular Biomarkers Biomarkers MolecularMolecular biomarker biomarker is is an an umbrella umbrella term term for for al alll biomarkers biomarkers that that can can be be measured measured based based on on the the biomarker’sbiomarker’s molecularmolecular characteristic. characteristic. The The detection detecti ofon biomarkers of biomarkers has been has the been backbone the backbone for screening for screeningand diagnostic and diagnostic aid in medical aid in laboratories. medical laboratories. They are They routinely are routinely carried out carried using out patient using samplespatient samplessuch as tissuesuch as biopsy, tissue blood, biopsy, urine, blood, and urine, other and biological other biological samples. samples. One of the One most of commonthe most detectioncommon detectionmethods usedmethods in clinical used laboratoriesin clinical islaboratories immunohistochemistry is immunohistochemistry (IHC), which detects (IHC), cellular which markersdetects cellularand phenotypes markers specificand phenotypes to certain diseasesspecific to through certain staining diseases with through highly staining specific antibodieswith highly [20 specific]. Since antibodiesIHC can be [20]. done Since on bothIHC freshcan be and done formalin-fixed on both fresh tissues, and itformalin-fixed serves as a convenient, tissues, it simple,serves as and a convenient,cost-effective simple, platform and for cost-effective clinical diagnostics platform [21]. for However, clinical there diagnostics are several [21]. limitations. However, Although there are it severalis not di limitations.fficult to obtain Although commercially it is not difficult produced to obtain antibodies, commercially there are produced no standard antibodies, guidelines there for are the novalidation standard of guidelines these antibodies. for the The validation interpretation of thes ofe theantibodies. slides by The pathologists interpretation can vary of the considerably slides by pathologistsand is affected can by vary how considerably the tissue was and processed, is affected stored, by how and the handled. tissue was This processed, is exacerbated stored, by and the handled.presence This of intratumoral is exacerbated biomarker by the presence heterogeneity of intratumoral that can cause biomarker discordance heterogeneity in the classification that can cause of discordancecancer [22]. Furthermore,in the classification the lack of ofcancer standardized [22]. Furthermore, guidelines the for lack quantitative of standardized and semiquantitative guidelines for quantitativescoring raises and concern, semiquantitative especially when scoring it involves raises concern, clinical decisions. especially While when the it Americaninvolves clinical Society decisions.of Clinical While Oncology the American (ASCO) and Society College of ofClinical American Oncology Pathologists (ASCO) (CAP) and College issued guidelinesof American for Pathologiststhe handling (CAP) of biopsy issued tissues guidelines of breast for cancerthe handli patients,ng of guidelinesbiopsy
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