Sagar Lonial, M.D. is associate professor, hematology/medical oncology at Emory University in Atlanta. Dr. Lonial, a recipient of a Translational Research Program grant from LLS, is studying a combination therapy for patients with myeloma and other blood cancers.

What is the biomedical problem/issue that you are trying to resolve?
The proteasome is a piece of cellular machinery that removes unnecessary proteins from cells. But in some blood cancers, such as myeloma, the proteasome may function abnormally. The targeted drug Velcade (bortezomib) works for many myeloma patients by inhibiting the proteasome. But myeloma and other cancer cells can resist being killed by Velcade. Our group is trying to better understand how cancer cells become resistant and if we can overcome that resistance, especially by making Velcade more effective in combination with other drugs.

What’s novel or innovative about your approach?
Our approach is novel because we are trying to choose drug combinations based upon preclinical evidence gathered in our laboratory studies, rather than just randomly combining available drugs. Our preliminary findings suggest that we can really improve the efficacy of Velcade for patients with myeloma by combining it with Zarnestra (tipifarnib), an experimental drug that has been shown to inhibit an enzyme that can cause excessive growth of cancer cells. Zarnestra really does not kill many myeloma cells when used alone, but the anti-myeloma effect of the combination is quite striking in laboratory tests.

How will your work one day help patients?
We are currently enrolling patients in an early phase clinical trial based upon our laboratory data, and have seen responses among patients with myeloma who were resistant to Velcade as a single agent. We are now testing higher dose levels and hope to show that the combination is measurably more effective in patients than Velcade alone, as is true in laboratory tests.

Are you close to clinical trials?
The trial is open; 23 patients have been enrolled so far.

I think the excitement is around the addition of these new agents in treatments for patients with newly diagnosed disease where combinations might be able to result in complete remissions, and possibly even durable complete remissions. In the setting of relapsed disease, new combinations may allow us to treat patients with lower doses of each respective agent to reduce side effects, or use standard dosing but with improved outcomes as measured by number and duration of responses.

What are some of your hobbies and non-research interests?
My hobbies are golf and wine tasting, only one of which I enjoy doing with my kids. I also enjoy traveling, which I am able to do a bit through the myeloma community.

Source: lls.org (eNewsLine)

Types of Childhood Cancer

Leukemia

Leukemia is a cancer of the bone marrow and tissues which produce the circulating blood cells. Leukemias are the most common childhood cancers. Types of leukemia include:

• Acute Lymphoblastic Leukemia (ALL): The most common childhood cancer. Almost 75% of children with leukemia have ALL, a cancer of the lymphoid cells in the bone marrow and the lymphoid organs of the body. They are involved in the body’s immune system.
• Acute Myelogenous Leukemia (AML): AML (also called acute myeloid leukemia, acute nonlymphatic leukemia or ANLL) is cancer of the myeloid blood cells which are produced in the bone marrow and which help fight bacterial infections.

Cancers of the Central Nervous System

• Brain tumors: There are many types of brain tumors; the most common are called gliomas.
• Neuroblastoma: is a cancer of the sympathetic nervous system which most often originates in the adrenal glands above the kidney.

Sarcomas

Sarcomas are cancerous tumors involving the bones and soft tissues.

• Bone cancers

  • Osteosarcoma: the most common type of bone sarcoma. These tumors often are located at the growing end of the long bones of the extremities, close to the joints.
  • Ewings Sarcoma: a bone cancer that often appears in the middle of the bone. Commonly found in the thighs, hipbones, upper arms and ribs.

• Soft Tissue Sarcomas:

  • Rhabdomyosarcoma: a soft tissue sarcoma that develops in muscles. Most often found in the head, neck, kidneys, bladder, arms and legs.

Lymphomas

Lymphoma is a tumor of the lymph tissues, which are part of the immune system. Types of lymphoma include:

• Hodgkin disease or Hodgkin’s lymphoma: affects lymph nodes nearer to the body’s surface, such as in the neck, armpit and groin area.
• Non-Hodgkin Lymphoma: affect lymph nodes found deep within the body. There are many types of lymphoma, include Burkitt’s, non-Burkitt’s, and lymphoblastic lymphoma.

Liver Cancers

Liver cancer is an abnormal growth (tumor) in the liver.  The most common forms of liver cancer in children are:

• Hepatoblastoma
• Hepatocellular carcinoma

Cancers of the Kidney

• Wilms tumor: also called nephroblastoma
• Clear Cell Sarcoma

Other Types of Cancers

• Retinoblastoma: is a malignant tumor of the retina (a thin membrane in the back of the eye).
• Germ Cell Tumors: Germ cell tumors appear most commonly in the testes, the ovaries, the area at the bottom of the spine (sacrococcygeal) and in the middle of the brain, chest or abdomen.

Progress in Childhood Cancer

Since the mid-1950s, cooperative research has improved the survival rates for childhood cancer from less than 10% to almost 80% overall. Cure rates vary according to each specific type of childhood cancer. Some types remain very difficult to cure. All cure rates need to be improved.

Multi-institution cooperative research of major scope has also paid dividends well beyond childhood cancer, contributing to:

• understanding the abnormal biology of cancer cells,
• treatments for adults with cancer,
• developing principles of team management for other diseases of children and adults, and
• pioneering the enormous advantages of multi-institution cooperation in clinical research.

Important Steps in the History of Childhood Cancer Research

Multi-institution Cooperation in Clinical Trials

One of the most important contributions to developing better treatments for children with cancer was the formation by the National Cancer Institute of the first group of hospitals that agreed to cooperate in clinical trials of new drugs that had been developed to treat acute leukemia, the most common cancer among children.

Cooperative clinical trials of chemotherapy for acute leukemia were begun at seven hospitals scattered through the U.S. in 1955. Research grant support was provided by the NCI.

Leukemia Chemotherapy

The original seven member hospitals of the group were convened by the National Cancer Institute to cooperate in conducting trials of new chemotherapy for acute leukemia. This was the optimal way to quickly evaluate new chemotherapies that showed promise in laboratory experiments on leukemia cells. The first cancer clinical trials cooperative group treated only one type of childhood cancer; acute leukemia, using only one modality of treatment: chemotherapy. The era of chemotherapy for cancer had been heralded by discovery of several chemical agents that could eliminate leukemia cells from the bone marrow and circulating blood in children with acute leukemia. This was a breakthrough that demanded rapid trials of many potentially effective new agents. The NCI developed groups of institutions to cooperate in joint conduct of clinical trials to perfect new chemotherapies being developed in many laboratories. National cooperation in clinical research was very successful. Many new agents were found to be effective in treating acute leukemia and gradually the remissions of leukemia extended from several months to several years. At that time, however, there was little discussion of cures.

Treatment of Solid Tumors in Children

Due to the success of chemotherapy in acute leukemia, it was imperative to try chemotherapy against the cancers of solid organs. The NCI supported childhood cooperative research group pediatric surgeons, pediatric radiation oncologists and pediatric pathologists to their membership, in order to combine surgery, chemotherapy and radiation therapy in treating the solid malignant tumors of children. After a few years, the group required multi-disciplinary teams to be formed at each member institution. The group which had been formed originally to test chemotherapy for leukemia, was significantly re-organized to include the principal medical disciplines needed to diagnose and treat solid tumors of children as well as leukemia.

Multi-Disciplinary Team Care of Childhood Cancer

Childhood cancer groups developed special national studies combining surgery, chemotherapy and radiation therapy to treat certain types of cancers of the kidneys and muscles which occurred mainly in children. Combined modalities of treatment, including surgery, chemotherapy and radiation therapy were found to produce the best results for these childhood solid tumors after surgical removal of as much of the tumor as possible.

New treatments based on immunology, bone marrow and stem cell transplantation and newer treatments derived from molecular biology and genetics are now in increasingly wider use as the research horizon expands. Multi-institution clinical trials by cancer clinical researchers are the most efficient way to apply new laboratory discoveries to advance diagnosis, selection of the most appropriate treatment and, increasingly, to prevent cancer.

The best response and survival rates of children with cancer have been achieved by treatment according to a clinical trial protocol at a cooperative group member hospital with experience in conducting multi-disciplinary clinical trials. To participate in cooperative national clinical trials, a member institution now must have a multi-disciplinary team of experts that can comply with all diagnosis, treatment, supportive care and laboratory requirements of cooperative clinical trial protocols and provide combinations of treatments adjusted to the needs of each child.

Laboratory and Translational Research on Childhood Cancer

Research in cellular and molecular biology, genetics, immunology and epidemiology has become an important aspect of cooperative group cancer research. To improve diagnostic evaluation, to develop new treatments and to evaluate how they affect cancer cells, many group member institutions developed laboratory research programs to further accelerate progress in diagnosis, treatment and cure of all types of cancers that attack children. The cooperative groups have incorporated laboratory research programs in many basic sciences. These have led to new understandings of how normal cells transform into cancer cells and how to develop therapies to overcome that process without harm to normal cells and tissues. Current treatments that directly affect only cancer cells are referred to as “targeted” therapy. Many of the important discoveries of the Human Genome Project have led to better diagnosis and treatments.

The majority of the laboratory researchers conducting research related to childhood cancer are located at academic medical centers throughout the U.S. and Canada. When they produce laboratory research findings which have potential application to diagnosis, treatment, supportive care or prevention of childhood cancer, they have ready access to their clinical colleagues on the COG team at their institution. One of the primary objectives of the COG is to facilitate the translation of important laboratory research to clinical applications to benefit children with cancer. This has been a research priority of COG institutions for several decades.

The Concept of Total Cure

A major emphasis for the past two dozen years has been on improving the quality of life for patients cured of cancer during childhood. The modern definition of “cure” for children goes far beyond achieving disappearance of the evidences of cancer. It now includes the goals of psychosocial, educational, and occupational reintegration of the child into a successful life. In social terms, the impact of this achievement is considerable: The cure of a child saves an entire lifetime.

Taken from http://www.curesearch.org/

Welcome to Day 6 of the Blogging for Blood Cancer event! Today’s prize is a Princess purse and ribbon tutu from Pretty Posh Princess. Yesterday’s winner was commenter #9 Denise who knew there were 600 members of Friends of Heroes in 2007.

To qualify to win, leave a comment with an answer to the question after reading the post.

Why is pediatric research so important?

• Joseph Burchenal, M.D., established the chemotherapy program at New York’s Memorial Sloan-Kettering Cancer Center, now the standard model around the world
• William Dameshek, M.D., considered one of the world’s leading hematologists, was among the first to identify an effective chemo agent.
• Brian Druker, M.D., was a leader in the development of Gleevec®, a revolutionary non-toxic pill that treats chronic myelogenous leukemia and other cancers.
• Emil Frei III, M.D., pioneered curative treatment of acute lymphocytic leukemia, resulting in prolonged survival.
• Robert Peter Gale, M.D., noted leukemia researcher and bone marrow transplant expert who helped clone the gene that causes chronic myelogenous leukemia and developed drug treatments for acute myelogenous leukemia and other leukemias.
• George Hitchings, Ph.D., helped develop 6-mercaptopurine and thioguanine, two of the first and most widely used leukemia drugs.
• George Santos, M.D., was a pioneering bone marrow transplant expert.
• E. Donnall Thomas, M.D., first scientist to successfully perform a bone marrow transplant between two humans.
• C. Gordon Zubrod, M.D., is considered the “father of the clinical trials concept in oncology.” (Our History. 2006. The Leukemia & Lymphoma Society. Retrieved from http://www.leukemia-lymphoma.org/all_page?item_id=221384)

In 1960-63, when compared to a person without leukemia, a patient had a 14 percent chance of living five years. By 1975-77, the five-year relative survival rate had jumped to 35 percent. By 2002, the survival rates have increased dramatically large impart due to the wonderful research conducted by The Leukemia & Lymphoma Society and other organizations like them.

• Acute lymphocytic leukemia (ALL): 65.2 percent overall; 90.5 percent for children under 5;
• Acute myelogenous leukemia (AML): 20.4 percent overall; 53.1 percent for children under 15
• Non-Hodgkin’s lymphoma: 81.9% for children under 19
• Hodgkin’s lymphoma: 95.1% for children under 20.
• (Leukemia Facts & Statistics. 2006. The Leukemia & Lymphoma Society. Retrieved from http://www.leukemia-lymphoma.org/all_page?item_id=9346)

Even though these survival rates have significantly improved, until there is early detection, a method of prevention, and a cure for blood cancers, research is still desperately needed. Anything less than 100% survival rate just is not good enough, especially when you are talking about someone’s child.

ENTER TO WIN TODAY’S PRIZE:

For a chance to win, leave a comment with the name of the first scientist to successfully perform a bone marrow transplant between two humans by MIDNIGHT PST today.

[Hint, hint, hint: You will find the answer in this post. Wink, wink.]

You’ll also be entered for our grand prize to be drawn Monday for a $900 Timberland and Lacoste product assortment, courtesy of Samsonite. (Comments are moderated.) Make sure to stop back for more information and even more chances to win!

Imatinib Effective Over Long Term in Refractory Leukemia
Imatinib mesylate (Gleevec^®) therapy shows lasting safety and efficacy in chronic-phase chronic myeloid leukemia patients in whom interferon-alpha treatment has failed.

Taken from LeukemiaLinks, your monthly source of leukemia news, research updates, clinical trials and events sponsored by The Leukemia & Lymphoma Society (LLS). For even more information, regularly visit their Patient Services and Disease Information Web sections.

For more information, visit http://www.friendsofheroes.org or contact teamleaders@friendsofheroes.org

As parents, we go to great lengths to protect our children from harm – starting at the moment they’re born or even at the moment we have a positive pregnancy test. We buy baby gates and monitors. We watch the latest toy recalls. We teach our kids to not accept candy or rides from strangers and to “just say no”.

However, when a family hears the diagnosis that their child has cancer, it can be quite overwhelming, if not devastating.

Childhood Cancer Affects the Whole Family

“Childhood cancer is a family disease since it affects everyone in the family’s system… this includes families, school and friends, the total environment of the child,” says Nancy Cincotta¹, MSW, LCSW, ACSW, BCD and Psychosocial Director at Camp Sunshine [http://www.campsunshine.org].

Cincotta encourages families find a group as a way to cope and find support. “The Leukemia & Lymphoma Society is a tremendous resource for families on back to school initiatives, on information services for financial support.”

When we raise money for Light The Night, we help support families as they deal with first diagnosis and endure their cancer journey.

Through the Patient Services programs and resources such as patient education programs and the Information Resource Center, the Society made 4.2 million contacts with patients, caregivers and healthcare professionals in FY’06. The Family Support Groups and First Connection served nearly 16,000 people.

This support is free to families because of money donated through Light The Night and other Society programs.

Survivorship Issues

Currently, there are approximately 270,000 living survivors of their childhood cancer and their cancer treatment². This group continues to grow as advanced, less-toxic treatments are developed.

“Newer therapies are based on improved understanding of the potential treatment complications of those earlier therapies,” said Leslie L. Robison³, PhD, Chair of the Department of Epidemiology and Cancer Control at St. Jude, principal investigator of CCSS, and senior author of the study.

While hopeful, it’s expected that three-quarters of this group will develop a chronic health problem and 40 percent may experience a “serious, life-threatening, disabling, or fatal condition” within 30 years of the initial cancer diagnosis.

Until targeted-cell therapies advance and only the cancer cells are affected and not the normal tissues or more advanced treatments are developed, many survivors will continue to be afflicted with cognitive and late effects from radiation and chemotherapy.

For more on cancer survivorship and a continuing series on childhood cancer, visit http://www.leukemia-lymphoma.org/all_page?item_id=74410.

Future Treatment Options and Prevention for Childhood Blood Cancer

Thirty years ago, a child’s cancer diagnosis most likely meant a death sentence. But, with years of research, a family can now get through cancer treatment with increased hopes for survival. A cure for blood cancers still has not been discovered, but the future holds hope for a breakthrough with continued funding and research.

For the past three years, Joseph Wiemels, PhD, has been the recipient of funding because Friends of Heroes and affiliates raised over $100,000 each year to achieve a grant-naming opportunity bestowed by the Society.

“Wiemels is acknowledged as a mainstream expert on the origins of acute lymphoblastic leukemia.”⁴

He led the research discovering that most dormant childhood leukemias begin before birth and he continues to research in hopes to identify the causes – dietary, environmental, or otherwise – that could result in the potentially harmful genetic mutation.

“Unraveling the causes and timing of the mutations that lead to leukemia, may allow us to predict and prevent this devastating disease,” said Wiemels⁵.

What can we do?

Once again in 2007, Friends of Heroes hopes to reach the $100,000 needed for the grant-naming opportunity so we can continue to support Dr. Wiemels’ research. We will also be supporting valuable Patient Services with the money we raise for Light The Night.

This September, help us honor Childhood Cancer Awareness Month. Please join us as a donor, a walker or an affiliate team so we can continue to help pediatric cancer patients and their families. Your help makes a difference to improve the lives of patients and can fund the necessary research to find a CURE!

By National Team Co-Captain Jenn B.

Sources:

¹ http://www.leukemia-lymphoma.org/graphics/National/EI2530DFinalTranscription.pdf

² http://www.accessmedicine.com/content.aspx?aid=2800901

³ http://www.mskcc.org/mskcc/html/71319.cfm

⁴ http://pub.ucsf.edu/today/cache/feature/200703082.html

⁵ http://www.ucsfhealth.org/adult/health_library/news/2002/05/9747.html

Career Development: Scholar in Clinical Research

Joseph Wiemels, PhD – 2004 (Active) – 2634-04

The Regents of the University of California, San Francisco San Francisco, CA US

Etiology and Natural History of Pediatric Leukemias with t(12;21) TEL-AML1 Translocations

Leukemia is the most common cancer in childhood. Despite many advances in the treatment of childhood leukemia, the disease remains a tragic circumstance in suffering and mortality. The advances in treatment are not matched by advances in discovering the cause or means to prevent the disease.

Leukemia is associated with genetic changes in certain types of blood cells, and we have discovered that one type of change, chromosomal translocations, very often occur before the child is born. These translocations are quite common among children, most of who never get leukemia. However, we have very little information about the genetic changes that occur after birth and how these changes ultimately cause leukemia.

We currently propose to apply new techniques in the field of cancer genetics to identify the identity and exact sequences of these secondary genetic events in the most common type of leukemia, those with the translocation t(12;21).

These techniques, termed “array comparative genomic hybridization” and “inverse polymerase chain reaction” will be used within a comprehensive epidemiology study of childhood leukemia in Northern California. We will use our “molecular forensic” techniques in concert with traditional epidemiologic methods to discover the causes of leukemia for the purposes of developing preventative strategies.

From: lls.org