Customer Reviews

From Melanocytes to Melanoma: The Progression to Malignancy

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Hearing and Leong have prepared an excellent review of the state of the art in the underlying genetic mechanisms involved in melanoma. The book is a lengthy but highly readable collection of chapters prepared by major contributors to the field.

The Editors state that the text is divided into three sections:

Part I: Development of melanocytes
Part II: Melanocyte Transformation to Melanoma
Part III: Primary Invasive Melanoma to Metastasis

Thus the authors try to follow the steps from development, transition and metastasis. In so doing the focus is on pathways, transcription factors, and the genetic errors which cause failure in normal homeostatic management of the melanocyte.

The strength of the text is its breath of authors and their insight. That also is its weakness since there is considerable overlap and some discussions are often just a bit too brief.

In Part I there is an excellent set of presentations on the development and life cycle of the melanocyte. As with the entire work there is primary focus on the cell and its internal pathways.

For example Chapter 3 is an excellent discussion of MITF, the signalling that facilitates it via '-catenin, and its impact on melanocyte lineage. This provides an introduction of the LEF/TCF transcription factors which will play a role again and again.

In Part II there are extensive chapters on the progression from melanocyte to melanoma. Chapter 7 is an excellent review of the signalling changes in melanoma.

Wnt5a is discussed at length in Chapter 7 and also there is an introduction to BRAF as well. Most of the key pathways and their constituents are discussed, and this adds to what has previously been introduced. The graphics are quite useful and the result provides the reader with a focus on the specifics of melanoma. To those familiar with these pathways from other cancers then there is a considerable amount of overlap, especially on seeing PTEN as a common factor.

Chapter 9 is a critical chapter for the understanding of melanoma. The E-cadherins are the proteins which bind the melanocytes to the keratinocytes in the basal layer. This chapter discusses what happens as they lose their ability and are replaced by N-cadherins. The melanocyte no longer adheres to where it is supposed to and starts wandering. That is one of the characteristics of a malignancy common to all cancers. It is especially well described in this Chapter.

Chapter 11 describes the initiation of melanoma as a process. On p 189 there is the common Vogelstein stepped process gong from a benign melanocyte thru dysplasia and on to SSM and Vertical phase and metastasis. The author clearly states that the steps may not occur sequentially. Thus the normal thought of E-cadherin loss being a final step may actually be a step occurring in say a melanoma in situ, although that is still speculative. The questions left unanswered are still what specific changes caused what mutations where and what is the common sequence.

Part III looks at the issue of metastasis with emphasis on pathway elements. This is an extensive discussion of where the literature was at when published but does not reflect the progress made with BRAF and its management, limited as it may still be.

Chapter 31 raises a key issue worthy of further discussion. Namely, the classic way a patient approaches this process is first a visit to a general practice or family physician, then a referral to a dermatologist who removes the suspected lesion, which is sent hopefully to a dermatopathologist who treats and processes the lesion. If positive for melanoma then after a few more meetings the patient may be referred to a melanoma specialist. By then the ability to determine many of the genetic markers useful for determining the prognosis have been lost. The authors make several clear points on this issue which may become a more significant factor in treatment as we go forward.

Some topics worth discussing but not included in my opinion are:

Stem Cell Issues: What of the stem cell theory and how does it apply to melanoma. There is some discussion on stem cells and growth factors but the broader issue of there being a stem cell is not covered.

Dynamics of Pathways: How do these pathways change in time. This is the dynamics of pathways. There is a reference to the use of differential equations to understanding them but it would have been useful to have included some specific discussions in a separate chapter.

Dynamics of Mutations and Cell Alterations: What happens when, namely there should be a discussion of the steps leading to specific changes leading to the pathway changes and then to a malignancy.

Methylation, microRNAs and other Epigenetic Factors in Changing Expressions: There is some discussion on methylation but none that I could see on microRNAs or other epigenetic factors. There is a considerable body of knowledge developing and its inclusion would have been useful

SNPs and Their usefulness in Identifying Malignancy:

Specific Approaches to Treatment; Immunological and Pathway Targeting: This is the best place to have introduced the BRAF treatment. Also there has been decades of work on the immunological side and it is covered somewhat.

Some of the minor apparent weaknesses of the book are:

Multiple Authors with Multiple Repeats: This is a good and bad issue. The book is a collection of writings by multiple specialists and each is superbly done.

Dated: Like any work in this field it gets aged quickly. For example all of the recent work on BRAF and its treatment postdates the work although it is clearly anticipated.

Detail: Since each author somewhat repeats and begins again, there could have been more depth in each chapter if there had been tighter coordination. This is a nit but it is the constant challenge of a collaborative work. Notwithstanding this really is a desire to have it expand.

Overall this is a superb contribution and an essential work to be on the desk of anyone examining pathways and cancer.