Fast Facts: Molecular Profiling in Solid Tumors

By P. Cheema, E. Garralda, B.S. Sheffield and P. Pisapia

Identifying tumor-specific molecular aberrations via molecular profiling is vital for the use of targeted therapies. Understanding a patient’s unique tumor genetics provides predictive and prognostic information that enables a personalized care plan to be put in place, improving outcomes and minimizing ineffective treatments. 'Fast Facts: Molecular Profiling in Solid Tumors' provides a firm knowledge foundation of somatic molecular profiling methodologies, key information to help with the use of molecular profiling in daily practice and advice on communicating with patients about molecular testing and results. Table of Contents: • Molecular profiling: the basics • Rationale for testing • Sample collection • Test selection and process • Interpreting the report • Talking to patients • Challenges and opportunities

• Language: English
• Publisher: S. Karger
• Release date: Dec 6, 2022
• ISBN: 9783318072129

Book preview

Introduction

The first targeted therapy for cancer – the estrogen receptor blocker tamoxifen – was approved in the 1970s.¹,² However, 2001 marked a major turning point in the treatment of cancer when the first tyrosine kinase inhibitor, imatinib, was approved to treat chronic myeloid leukemia and gastrointestinal stromal tumors by targeting BCR-ABL1 and c-KIT.³ That approval marked the beginning of a new era in anticancer drug development, with steadily growing approvals of targeted therapies for a broader array of cancers.⁴

Identifying tumor-specific molecular aberrations via molecular profiling is vital for the use of targeted therapies. Understanding a patient’s unique tumor genetics provides predictive and prognostic information that enables a personalized care plan to be put in place, improving outcomes and minimizing ineffective treatments.

All treating physicians need to know what test to perform and when it should be ordered, followed by correct interpretation of the results so that well-informed patient-personalized treatment decisions can be made. However, oncologists report varying confidence in their ability to use genomic findings appropriately.⁵,⁶ With rapid advances in targeted therapy approvals and molecular profiling methodologies, it is difficult to stay abreast of the latest recommendations, let alone catch up with the vast amount of information already available. Fast Facts: Molecular Profiling in Solid Tumors provides a firm knowledge foundation of somatic molecular profiling methodologies, key information to help with the use of molecular profiling in daily practice and advice on communicating with patients about molecular testing and results.

It is important to recognize that healthcare structures and the implementation of molecular profiling vary significantly from country to country. The content herein represents the collective expertise of the authors. It serves as a starting point to understand and use molecular profiling in the treatment of solid tumors and should be complemented with information and recommendations specific to local settings.

References

1.Jordan CV. Tamoxifen: a most unlikely pioneering medicine. Nature Rev Drug Disc 2003;2:205–13.

2.Yan L, Rosen N, Arteaga C. Targeted cancer therapies. Chin J Cancer 2011;30:1–4.

3.Savage DG, Antman KH. Imatinib mesylate – a new oral targeted therapy. N Engl J Med 2002;346:683–93.

4.Zhong L, Li Y, Xiong L et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther 2021;6:201–49.

5.Schwartzberg L, Kim ES, Liu D et al. Precision oncology: what, when, and when not? Am Soc Clin Oncol Educ Book 2018;37:160–9.

6.Singh BP, Britton SL, Prins P et al. Molecular profiling (MP) for malignancies: knowledge gaps and variable practice patterns among United States oncologists. J Clin Oncol 2019;37(15_suppl):10510.

1Molecular profiling: the basics

Molecular profiling in oncology commonly refers to the testing of tissue samples or biofluids (serum, plasma, urine, etc.) with the aim of identifying tumor-specific molecular alterations (that is, biomarker status) that provide a distinctive ‘genetic signature’.¹

Aims of molecular profiling

Established applications. As of 2022, a fast-growing number of biomarkers (discussed in the following sections) can be identified via molecular profiling primarily to support diagnosis, drive appropriate targeted therapy, qualify the patient for a clinical trial, inform disease progression and prognosis or gauge treatment response.

Patient stratification for targeted therapies. Matching molecular alterations to a targeted therapy improves clinical outcome and has become the standard of care in several solid tumors, including breast, lung, melanoma and colorectal cancers.

Case study 1.1 – patient stratification for targeted therapies against metastatic colon cancer²

CDX2, caudal-type homeobox 2 transcription factor; CK7/20, cytokeratin 7/20; ctDNA, circulating tumor-derived DNA; EGFR, epidermal growth factor receptor; NGS, next-generation sequencing; TTF-1, thyroid transcription factor 1.

Prognosis of disease course. Precise classification of tumor subtypes correlated with known disease progression and prognosis can inform treatment planning and palliative care.

Case study 1.2 – unfavorable prognosis for colorectal cancer⁴

EGFR, epidermal growth factor receptor.

Gauging response to chemo- or immunotherapy. The use of ineffective treatments can be minimized based on the presence of biomarkers that predict non-responsiveness or the development of resistance.

Case study 1.3 – chemotherapy for colon cancer