Whenever we talk about practicing precision medicine in oncology, next-generation sequencing quickly becomes part of the conversation. It’s difficult to imagine a treatment plan more customized than one based on a detailed molecular profile of that individual patient’s tumor.

Yet the intricacies of translating these advances in our understanding of tumor biology into daily clinical practice are daunting in their own right.

That theme is evident throughout this issue. Our cover story, “Is Next-Gen Sequencing Ready for Prime Time?”, describes a debate between two leading researchers about the clinical utility of molecular profiling in the management of patients with breast cancer, particularly in those with metastatic disease.

It is important to note that the eventual utility of genomic testing was not in question; the issue in this debate was the relevance of such testing to the treatment of patients today. The discussion turned on whether the information generated through genomic profiling is definitive enough and immediately actionable for practicing oncologists to put it to work for current patients. We’ll let you decide.

Our editor-in-chief, Maurie Markman, MD, 

addresses another issue in genomic tumor profiling

: obtaining appropriate tissue samples for solid tumors to conduct nextgeneration sequencing. Research is under way on whether “liquid biopsies” that use blood-based biomarkers or fine-needle aspiration can provide the needed solutions.

As more next-generation testing instruments hit the market, questions about how the information that they produce will be used in the clinic are likely to become more pressing. Already, there are indications that payers are requiring that such diagnostics lead to a treatment option before they agree to cover the bill for the assays.

We plan to keep you up to date on the latest developments concerning all facets of these emerging technologies, particularly through our extensive coverage of Physicians’ Education Resource (PER) meetings, where leading researchers tackle these matters.

We encourage you to let us know what is on your mind. As always, thank you for reading.

Articles

Intricacies of translating these advances in our understanding of tumor biology into daily clinical practice are daunting in their own right.

Much Promise, Many Issues

Although there have been significant advancements in the treatment of patients with chronic lymphocytic leukemia (CLL) during the past decade, oncologists and hematologists were missing a tool that has become increasingly available for attacking other malignancies: an oral small-molecule inhibitor.

 not only that the approval of ibrutinib (Imbruvica) means that such an agent is now available for treating certain patients with CLL, but also that several classes of molecularly targeted drugs are in development.

In short, management of patients with CLL is entering a new era of precision medicine.

We’re using that term as a more definitive and, we hope, more meaningful description for oncology therapeutics aimed at specific cellular processes. In every tumor type, the introduction of therapies that can mount a more precise attack on the underlying biological processes of cancer has been a milestone for progress.

An important next step has been the consideration of biomarkers that may indicate which patients are optimal candidates for a new agent.

Elsewhere in this issue, we relate the story of how such progress was achieved in another hematologic malignancy, chronic myeloid leukemia (CML). Brian J. Druker, MD, tenaciously pursued the concept that a small molecule that inhibits the tyrosine kinase created by the Philadelphia chromosomal abnormality in CML would be a successful strategy for attacking the malignancy. The result was a therapy that many observers say has helped change the natural history of CML and has paved the way for other tyrosine kinase inhibitors.

It is much too soon to predict what kind of an impact the new agents in development for CLL will have on patients with the disease. There is much excitement over the clinical benefit and quality-of-life improvements that some patients are experiencing already as a result of ibrutinib therapy.

We do know that practicing oncologists carefully weigh multiple factors before administering a new therapy to a patient.

We hope the material in this issue provides information that helps you ponder the options— thoughtfully and with precision.

Management of patients with CLL is entering a new era of precision medicine.

Reaching a New Milestone

The big story in oncology research for the past several years has been the emergence of immunotherapy as a viable strategy for attacking many different tumor types.

Yet while the headlines and the financial markets grow frothy with enthusiasm, practicing oncologists know that there’s much more work that must been done before patients can reap the benefits of these advances.

, we report on an emerging body of knowledge that is coalescing around the optimal use of immunotherapies in the clinic. Our cover story, “

New Paradigms Emerge for Translating Immunotherapy Into Broad Clinical Use

,” offers the insights of some of the world’s leading immunologists.

One of the most fascinating aspects of these new paradigms is the concept of scoring a tumor based on immune status in much the same way as patients are now staged according to the TNM system. In the not too distant future, we likely will have the tools to evaluate a patient’s immune status at diagnosis and thus better guide the use of an immunotherapeutic agent.

Perhaps some day soon, oncologists will be expanding their patient workups to include an “immunoscore.”

Elsewhere in this issue, we present news and views on other pressing matters confronting the development and implementation of potentially beneficial new drugs. Our coverage of the 2013 San Antonio Breast Cancer Symposium includes 

, which may serve as a model for evaluating novel treatment regimens in a more efficient time frame. And, Maurie Markman, MD, our editor-in-chief, discusses the ways in which the 

“superiority” standard in clinical trials

 can become a barrier for new therapies that stumble over a statistical hurdle yet still help patients.

Although much progress has been made in cancer science and treatment, vast areas of uncharted territory remain. Our goal is to keep oncology specialists up to date on integrating emerging therapeutics into their practices. Please let us know what you would like to see in the pages of this magazine.

The big story in oncology research for the past several years has been the emergence of immunotherapy as a viable strategy for attacking many different tumor types.


Taking the Next Step

There’s no question that the advent of molecularly targeted strategies in anticancer therapy have revolutionized the understanding and practice of oncology, but it also is clear that those gains have not been uniformly realized throughout the range of malignancies.

The disparities in the pace of personalized cancer advancements among different tumor types echo throughout this issue of 

For example, researchers have discovered a series of effective agents for certain hematologic malignancies, starting with rituximab (Rituxan), which in 1997 became the first molecularly targeted cancer drug to gain FDA approval. That record of success is continuing. 

Our report from the 2013 American Society of Hematology Annual Meeting

 details a veritable bounty of targeted agents for the treatment of patients with chronic lymphocytic leukemia, opening up the field with fresh possibilities for drug development and patient care.

By contrast, little progress has been made in integrating targeted therapies into the treatment of patients with stage III non-small cell lung cancer (NSCLC), as described in 

 at the recent 8th Annual New York Lung Cancer Symposium. Paradoxically, this uncertainty comes amid advances in targeted treatments for stage IV NSCLC.

Then we come to pancreatic cancer, where the impracticality of conducting clinical trials for molecularly defined subsets from the inherently smaller patient pools of less common cancers is becoming abundantly clear. Maurie Markman, MD, our editor-in-chief, 

 that a given therapy may become clinically less relevant in the years it takes for a traditional, full-fledged evaluation in a clinical trial.

The underlying message here is that more research—and more innovation&mdash; are needed. The oncology research and advocacy community has been fighting an increasingly frustrating and wearisome battle for more federal funding.

We’d like to add our voice to that campaign.

Although practicing oncologists may be far from the pressures of raising money for laboratory and clinical studies, they see the results in the tools they have to treat patients.

Certainly, the care of patients with cancer will not be improved solely by throwing money at research. Yet the proper support of innovation is vital to the discovery process that has brought us so far in certain cancers yet still so far away in others.

Please let us know your thoughts on these matters and, as always, thank you for reading.

There's no question that the advent of molecularly targeted strategies in anticancer therapy have revolutionized the understanding and practice of oncology, but it also is clear that those gains have not been uniformly realized throughout the range of malignancies.

Progress Remains Uneven

	The March issues of our oncology publications mark an exciting new era in the growth and maturity of our Oncology Specialty Group. Our partnership with the John Theurer Cancer Center gives us two renowned physician editors to lead our flagship publications, 

. More importantly, however, this partnership opens up a dialog with an entire facility of oncologists and allows our readers to have an open exchange with a team of experts—physicians, nurses, pharmacists, social workers, nutritionists, etc&mdash;whose collective goal is to provide extraordinary care to oncology patients.

	This new relationship brings us the breadth of expertise and professional exposure that will allow us to expand our coverage of the market and provide our readers with a comprehensive family of oncology publications that keep you engaged and informed.

	Thank you for reading…and stay tuned to see the positive effects of this exciting new partnership.

The March issues of our oncology publications mark an exciting new era in the growth and maturity of our Oncology Specialty Group. 

Partnership for Progress

	As 2010 has rolled along, the Intellisphere Oncology Specialty Group has aimed to uphold its mission of 

. In March, we covered The Third Annual Interdisciplinary Prostate Cancer Congress (IPCC) in New York, New York. The session’s theme was “Translating Advances into Clinical Practice,” and it featured renowned prostate cancer experts. ArcMesa Educators organized the well-attended event, which was open to urologists, radiologists, and medical oncologists. The IPCC was so well received that planning has started for next year’s Congress. Look for IPCC coverage in this issue; and for additional information, read our IPCC feature in the April 2010 issue of our sister publication 

	With the arrival of summer, we announced our new partnership with the National Coalition of Oncology Nurse Navigators (NCONN; 

). Recognizing nurse navigators’ importance to the oncology community, the Intellisphere Oncology Specialty Group has joined with NCONN to increase navigators’ access to professional and patient resources. Together we will also develop new resources, including patient handouts, articles, columns, interviews, videos, blogs, and more.

	Speaking of OncLive, in June we launched the 2.0 version of the flagship Website for 

. The easily navigable, redesigned site includes issue archives, conference coverage, blogs, informational videos, patient resource guides, and Web exclusives. We also created a social media platform that aggregates Twitter feeds from leading oncology organizations and physicians. Our goal is to maintain a Web presence that facilitates interaction and information exchange among the oncology community. To submit feedback and suggestions for the new OncLive, e-mail us at 

	As we head toward 2011 and beyond, we will also continue to update you on the best available oncology resources. For example, now through November of next year, our sister publication 

No Bones About It: The Pharmacist’s Role in Managing Cancer Therapy—Induced Bone Loss

), which you will find in this issue. We greatly appreciate your continued readership and hope that we have helped you keep in touch with the oncology community. Be sure to keep up with the latest issues of all our publications and visit OncLive.com regularly for important conference coverage from upcoming meetings and more.

As 2010 has rolled along, the Intellisphere Oncology Specialty Group has aimed to uphold its mission of Bringing the Oncology Community Together.

Truly Community-Based Oncology

	In recent years, the buzzwords in oncology cancer have been “personalized therapy,” in which the entire spectrum of cancer care is customized to the individual patient and his or her cancer. The National Cancer Institute  maintains a list of more than 200 types of cancer, which suggests achieving the goal of personalized care for every patient will not come easily.

	Advances in molecular cancer research, such as the mapping of the cancer genome (

), are helping the process along by allowing clinicians to determine molecular targets in patients’ tumors and select the appropriate targeted therapy—when there is one. One of the interesting things about this approach is the discovery that the molecular makeup of a tumor might be more important than where the tumor occurs. Along these lines, the FDA approved Herceptin (trastuzumab) for HER2-positive gastric cancer in October. Herceptin is already an established treatment for HER2-positive breast cancer, responsible for turning the aggressive often fatal disease into a manageable one for many women. Now, it may be poised to do the same for gastric cancer. It is the only approved targeted therapy for gastric cancer.

	The FDA also approved Sprycel (dasatinib) as a first-line therapy for adults with Philadelphia chromosome—positive chronic myeloid leukemia (CML). Ten years ago, personalized medicine was in its infancy and no targeted drugs existed for patients with CML. Now, patients can choose from among 3 options: Sprycel; Gleevec (imatinib); and Tasigna (nilotinib), which was also approved this year.

	Other targeted drugs are just over the horizon, like crizotinib in lung cancer and PLX4032 in melanoma. You cannot get much more personalized than immunotherapy vaccines, which are built for each individual patient.

	Where personalized medicine gets difficult is development. By definition, personalized therapies are intended for smaller patient populations. This means developing these drugs might be less profitable for pharmaceutical companies. With all the demonizing pharmaceutical companies get in the press, you might expect that they would stop trying to find cures for these small subgroups of patients with a cancer-causing genetic mutation. A few dire predictions have been floated that this might eventually come to pass; but from what we have seen at conferences like the recent 35th Annual Congress of the European Society of Medical Oncology and ASCO’s annual meeting, there is no sign of this so far.

In recent years, the buzzwords in oncology cancer have been "personalized therapy," in which the entire spectrum of cancer care is customized to the individual patient and his or her cancer.

Taking the Bull's-Eye Off the Pharma Companies

	Another year has come and gone, and it was a busy one for our group. We saw at least 10 new or expanded drug approvals for oncology products in 2010. Many spirited debates took place in this market this year, and several remain unresolved. While we will soon know the FDA’s decision on the use of Avastin (bevacizumab) in breast cancer, we will not find out whether the Centers for Medicare & Medicaid Services plans to follow the recommendation of its advisory panel and pay for Provenge until March 2011 (which will probably be sooner than when we know definitively how often “routine” mammography screening should occur).

	One aspect of oncology that appeared to unite everyone in 2010 was the need for greater personalization in cancer care. These days, it is nearly a foregone conclusion that every cancer contains multiple molecular or genetic therapeutic targets—even if researchers have yet to discover them. More often than not, the molecular/genetic discoveries are taking place before drug development, which can only benefit patients.

	At the recent 52nd American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, several studies concerning investigational targeted agents concluded with the words, “Based on these data, Company X plans to file a new drug application in 2011.” If the FDA approves even half of the applications that pharmaceutical companies anticipate filing in 2011, physicians will find themselves with far more treatment options for certain cancers. For example, in the past 6 months, hematologists went from having just 1 drug to offer patients with newly diagnosed chronic myeloid leukemia to a choice of 3, and findings from the ASH conference hint that 1 or 2 more might be just over the horizon.

	With 2011 being the 40th anniversary of President Nixon’s War on Cancer, quite a bit of ink is being spilled on grading the country’s achievements. These assessments often look at the final outcomes without considering the overall progress the field has made in such a short amount of time. While it is true that we have yet to find a cure for cancer, it is not for want of trying. We could publish a 100-page issue every week and still not review every new discovery in this expanding market. Those 10 new drug approvals in 2010 represent years of work and millions of dollars. And the fact that we have unresolved debates despite accumulating reams of data illustrates just how difficult some of those questions are to answer.

	Perhaps we won’t find a cure for cancer in 2011, but a few breakthroughs like those we have seen every year for the past several years will propel us to new discoveries that will bring us closer to our goal.

Another year has come and gone, and it was a busy one for our group. We saw at least 10 new or expanded drug approvals for oncology products in 2010.

Oncology Research Moves Us Closer to Our Goal

	While family history and lifestyle factors affect cancer risk, environmental factors also play a considerable role. You will no doubt recall the movie 

, which recounted the story of a law firm file clerk uncovering the dumping of hexavalent chromium, also called chromium 6, into the groundwater supply of Hinkley, a small town in southern California, by Pacific Gas & Electric. This finding and subsequent lawsuit led to one of the largest toxic tort injury settlements in US history, with $333 million in settlements awarded to approximately 600 Hinkley residents suffering from ailments such as breast cancer, Hodgkin lymphoma, lung cancer, brain-stem cancer, gastrointestinal cancer, kidney and ovarian tumors, and a host of other maladies as a result of being exposed to chromium 6. While similar cases have surfaced throughout the United States, and stories of chemicals being leached into drinking water by corporate entities may receive considerable attention by the media, there are naturally occurring environmental risk factors for cancer, such as radon, that receive comparably little attention but affect far more households.

	The ill health effects of radon have long been observed in miners, but it was not known to be a health risk in the general population until the 1980s. Radon is now known to be the second leading cause of lung cancer, and it may contribute to the development of other cancers as well, yet the only time this environmental risk factor may be brought to anyone’s attention is during a real estate transaction. January is National Radon Action Month, as designated by the US Environmental Protection Agency, and our cover story, “The Invisible Killer in Your Home: Understanding Radon, Testing, and Mitigation”, provides an overview of radon, testing methods, and locating a mitigation professional, while outlining some online resources that can help keep you, your family, and your patients informed and safeguarded from this environmental health hazard. 

	Our second feature story, “Mapping the Cancer Genome”, reviews some of the findings that cancer genome sequencing has yielded, including how environmental and lifestyle factors can increase cancer risk. Recently, researchers from the Wellcome Trust Sanger Institute in Cambridge reported the results of their study published in Nature, which compared the genetic sequence of small cell lung cancer cells and melanoma cells with normal cells taken from the same individuals. Through this analysis, the researchers were able to identify thousands of mutations in the cancer cells, with almost all mutations in the small cell lung cancer and melanoma cells being traced back to smoking and ultraviolet exposure, respectively. The researchers estimate that a typical smoker may acquire one mutation for every pack of cigarettes smoked, and one may surmise that exposure to other environmental toxins, such as radon, could lead to additional mutations, as research has shown that lung cancer risk from radon is especially high in smokers. As more cancer cells are sequenced, which is being made possible by the dramatic drop in gene mapping costs, the effects of various carcinogens and the role of genetic factors will be better understood, which will also lead to more effective, personalized treatments.

	In our From the Editor column, Dr Markman discusses electronic cigarettes, which have become increasingly popular, with some individuals using them as an alternative to traditional cigarettes because they are perceived to be healthier. As Dr Markman points out, however, assessment of these cigarettes has shown that they may contain other known carcinogens, as this industry is largely unregulated. Further, because electronic cigarettes are relatively new, their ill health effects are not yet known; thus, patients expressing interest in using electronic cigarettes should be warned of their potential dangers.

 and would love to know what you think of it, or if you have any topics you would like to see covered in an upcoming issue. You can send an e-mail to the editor, Christina Loguidice, at 

While family history and lifestyle factors affect cancer risk, environmental factors also play a considerable role. You will no doubt recall the movie Erin Brockovich, which recounted the story of a law firm file clerk uncovering the dumping of hexavalent chromium, also called chromium 6, into the groundwater supply of Hinkley, a small town in southern California, by Pacific Gas & Electric.

Mike Hennessy