Recent developments in the treatment of metastatic colorectal cancer

Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS/tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease. Even with few new targeted agents receiving approval in CRC, the incorporation of next-generation sequencing into clinical decision making represents an important step forward. Biomarkers such as BRAF mutations, microsatellite instability, and HER2 amplification represent promising molecular aberrations with therapies in various stages of development, and highlight the importance of companion diagnostics in supporting targeted agents. In this review, we will discuss the importance of incorporating biomarkers into clinical decision making and regimen selection in CRC. We will particularly focus on the recent evidence suggesting an important role for tumor location in selecting first-line therapy, the importance of recent advances in biomarker development and molecular subtyping, as well as recently approved agents (regorafenib and TAS-102) and promising targeted agents that have the potential to change the standard of care.

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Highly specific detection of KRAS single nucleotide polymorphism by asymmetric PCR/SERS assay

The Analyst ◽

10.1039/d1an01108a ◽

2021 ◽

Author(s):

Nana Lyu ◽

Vinoth Kumar Rajendran ◽

Jun Li ◽

Alexander Engel ◽

Mark P. Molloy ◽

...

Keyword(s):

Colorectal Cancer ◽

Decision Making ◽

Clinical Decision Making ◽

Clinical Decision ◽

Nucleotide Polymorphism ◽

Asymmetric Pcr ◽

Specific Detection ◽

Kras Mutations ◽

Single Nucleotide ◽

The Common

The molecular diagnosis of KRAS mutations has become crucial for clinical decision-making in colorectal cancer (CRC) treatments. Currently, the common methods for detecting mutations are based on quantitative PCR, DNA...

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INNV-28. MOLECULAR TESTING IN NEURO-ONCOLOGY – ASSESSMENT OF UTILITY AND PRACTICE PATTERNS. A SOCIETY FOR NEURO-ONCOLOGY MEMBERSHIP SURVEY

Neuro-Oncology ◽

10.1093/neuonc/noz175.569 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi136-vi136

Author(s):

Maciej Mrugala ◽

Susan Chang

Keyword(s):

Decision Making ◽

Clinical Decision Making ◽

Practice Patterns ◽

Clinical Decision ◽

Educational Programs ◽

Molecular Testing ◽

Targeted Agents ◽

Younger Patients ◽

Tumor Boards ◽

The Subject

Abstract BACKGROUND Molecular testing (MT) is utilized in neuro-oncology with increasing frequency. Multiple molecular panels are available providing a spectrum of information. We were interested in learning how this information is acquired, what are the practice patterns regarding this type of testing, how are the results utilized in patient care and how prepared neuro-oncologists are to interpret these results. METHODS We conducted a survey using the Society for Neuro-Oncology membership database. We developed a set of 13 questions and administered the survey to 2022 members using the online platform. RESULTS We received 153 responses (7.5% of membership). 89% percent of responders routinely order MT. Of those who do not order MT on all patients, 50% test younger patients and 57% midline tumors. 83% use MT in recurrent glioma. Other common indications for MT included: metastatic tumors, meningioma, medulloblastoma, ATRT. Majority (60%) use in-house panels, followed by Foundation One (35%), TEMPUS (13%), CARIS (10%) and other panels (23%). For 57% of respondents, the data from MT was somewhat useful and for 41% it was very useful. 78% used the results of MT for clinical decision-making. BRAF, EGFR/ALK, H3K27 mutations were most commonly used for treatment decisions. 50% of respondents have molecular tumor boards at their institutions and a majority of practitioners share the results of MT with their patients (95%). Respondents would like to see SNO-endorsed official guidelines on MT, organized lists of targeted agents available for specific mutations, a database of targetable mutations and clinical trials and more educational programs on the subject. CONCLUSIONS Molecular testing is neuro-oncology is commonly done. Many providers rely on the information for clinical decision making where appropriate. In-house and commercial genetic panels are equally used in practice. There continues to be a need for more education on the subject and development of neuro-oncology specific guidelines.

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Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-onset and Tumor Location: Two Main Criteria for Subclassifying Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20040968 ◽

2019 ◽

Vol 20 (4) ◽

pp. 968 ◽

Cited By ~ 6

Author(s):

Edurne Álvaro ◽

Juana M. Cano ◽

Juan L. García ◽

Lorena Brandáriz ◽

Susana Olmedillas-López ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Onset ◽

Age Of Onset ◽

Late Onset ◽

Cpg Island ◽

Low Frequency ◽

Tumor Location ◽

Molecular Characteristics ◽

Braf Mutations ◽

Rectal Cancers

Our aim was to characterize and validate that the location and age of onset of the tumor are both important criteria to classify colorectal cancer (CRC). We analyzed clinical and molecular characteristics of early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and we compared each tumor location between both ages-of-onset. In right-sided colon tumors, early-onset cases showed extensive Lynch syndrome (LS) features, with a relatively low frequency of chromosomal instability (CIN), but a high CpG island methylation phenotype. Nevertheless, late-onset cases showed predominantly sporadic features and microsatellite instability cases due to BRAF mutations. In left colon cancers, the most reliable clinical features were the tendency to develop polyps as well as multiple primary CRC associated with the late-onset subset. Apart from the higher degree of CIN in left-sided early-onset cancers, differential copy number alterations were also observed. Differences among rectal cancers showed that early-onset rectal cancers were diagnosed at later stages, had less association with polyps, and more than half of them were associated with a familial LS component. Stratifying CRC according to both location and age-of-onset criteria is meaningful, not only because it correlates the resulting categories with certain molecular bases, but with the confirmation across larger studies, new therapeutical algorithms could be defined according to this subclassification.

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Precision Approaches in the Management of Colorectal Cancer: Current Evidence and Latest Advancements towards Individualizing the Treatment

Cancers ◽

10.3390/cancers12113481 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3481

Author(s):

Rebecca A. Shuford ◽

Ashley L. Cairns ◽

Omeed Moaven

Keyword(s):

Colorectal Cancer ◽

Growth Factor ◽

Metastatic Colorectal Cancer ◽

Mismatch Repair ◽

Clinical Decision Making ◽

Growth Factor Receptor ◽

Clinical Decision ◽

Current Evidence ◽

Therapeutic Modalities ◽

Clinically Significant

The genetic and molecular underpinnings of metastatic colorectal cancer have been studied for decades, and the applicability of these findings in clinical decision making continues to evolve. Advancements in translating molecular studies have provided a basis for tailoring chemotherapeutic regimens in metastatic colorectal cancer (mCRC) treatment, which have informed multiple practice guidelines. Various genetic and molecular pathways have been identified as clinically significant in the pathogenesis of metastatic colorectal cancer. These include rat sarcoma (RAS), epithelial growth factor receptor (EGFR), vascular endothelial growth factor VEGF, microsatellite instability, mismatch repair, and v-raf murine sarcoma viral oncogene homolog b1 (BRAF) with established clinical implications. RAS mutations and deficiencies in the mismatch repair pathway guide decisions regarding the administration of anti-EGFR-based therapies and immunotherapy, respectively. Furthermore, there are several emerging pathways and therapeutic modalities that have not entered mainstream use in mCRC treatment and are ripe for further investigation. The well-established data in the arena of targeted therapies provide evidence-based support for the use or avoidance of various therapeutic regimens in mCRC treatment, while the emerging pathways and platforms offer a glimpse into the future of transforming a precision approach into a personalized treatment.

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Decoding Metastatic Colorectal Cancer to Improve Clinical Decision Making

Journal of Clinical Oncology ◽

10.1200/jco.19.01185 ◽

2019 ◽

Vol 37 (22) ◽

pp. 1847-1850

Author(s):

Justin Stebbing ◽

Harpreet Singh Wasan

Keyword(s):

Colorectal Cancer ◽

Decision Making ◽

Metastatic Colorectal Cancer ◽

Clinical Decision Making ◽

Clinical Decision

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Metastatic Colorectal Cancer: Current State and Future Directions

Journal of Clinical Oncology ◽

10.1200/jco.2014.59.7633 ◽

2015 ◽

Vol 33 (16) ◽

pp. 1809-1824 ◽

Cited By ~ 236

Author(s):

Marwan G. Fakih

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Targeted Therapies ◽

Clinical Decision Making ◽

Clinical Decision ◽

Cytotoxic Agents ◽

Braf Mutations ◽

Curative Intent ◽

Future Directions ◽

Unresectable Metastatic Colorectal Cancer

Substantial improvements have been made in the management of metastatic colorectal cancer over the last two decades. The overall survival of patients diagnosed with unresectable metastatic colorectal cancer has increased from approximately 1 year during the era of fluoropyrimidine monotherapy to more than 30 months with the integration of multiple cytotoxic agents and targeted therapies. More effective therapeutic combinations have increased the rate of curative-intent surgical resections, resulting in median survival in this subgroup that exceed 5 years. Here we review the landscape of systemic therapies for unresectable metastatic colorectal cancer during the current era of targeted therapies, review the effects of RAS and BRAF mutations on clinical decision making, and reflect on future directions for the treatment of metastatic colorectal cancer.

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