Some of the most exciting results in cancer medicine, in the last decade, have come about by treating relapsed patients with B cell lymphoma with their own T cells that have been modified to attack the tumor cells.  T cells in the body form part of the cellular immune response and they normally carry out a very important role in killing cells that are infected with viruses.

Most cancer deaths are due to metastasis – the spread of cancer from its site of origin to distant, vital organs, and the physiological damage caused by tumor growth in those organs. While the broad outlines of the process of metastatic spread are known, much of the details of the process remain poorly understood. 

Cancer therapies that specifically target the genetic alterations associated with subsets of advanced cancers have shown impressive success in the clinic.  Examples include ABL inhibitors fro chronic myelogenous leukemia, RAF inhibitors for BRAF mutant melanomas, EGFR inhibitors for EGFR mutant lung cancers, and HER2 inhibitors for HER2 amplified breast cancers. In each of these cancer paradigms, the treatments are often highly effective, leading to remarkable remissions that have a profound beneficial impact on patients. These successes have changed the landscape of the diagnosis and treatment of cancer for the foreseeable future.

The focus of the 2012 Forbeck Foundation forum was on the role of tumor metabolism on oncogenesis. While it has been known for over 50 years that the metabolism of cancer cells is distinct from that or normal cells, the reasons for this have only been emerging recently. Now that we are beginning to understand how and why metabolic pathways are altered in cancer, there is the potential to make use of this knowledge to improve cancer treatment. 

Cancer development is a multi-step process with mutations in proto-oncogenes and tumor suppressor genes playing a well-defined role. In this regard, cancer is a genetic disease. However, cellular mechanisms that control the differentiation state, survival and self-renewal of cancer cells are often independent of mutations in DNA sequence and are increasingly recognized as critical for tumor development and progression. These epigenetic mechanisms are largely a result of the multitude of chromatin modifications that control gene expression. Since epigenetic changes are largely reversible, there is significant hope that therapies targeting these modifications may be particularly effective anti-tumor agents. 

Cancer is a genetic disease. Increased cancer susceptibility can result from inherited mutations in tumor suppressor genes and oncogenes as well other genes. In addition, in both inherited and the much more common sporadic cancers, mutations arise that drive the development and progression of the cancer. Decades of research have led to an understanding of the types of pathways that become genetically and epigenetically compromised in cancer; however, a comprehensive understanding of the genetics of all tumor types is not yet available. In recent years it has been possible to bring to the clinic therapies that are targeted to genetic defects found in cancer. 

Primary tumors of the central nervous system are the leading cause of cancer death in children, and a tumor of growing incidence in adults, in whom it is equally difficult to treat. Only recently have researchers begun to understand the basic genetic derangements that play a central role in the growth of these tumors. In children, brain tumors are found in a variety of unusual types, some with unique and characteristic appearance on pathologic examination and in their clinical behavior. 

The immune system in our bodies keeps us safe from our environment that is full of bacteria and viruses. When we catch a cold it is our immune system that fights the infection. When we cut ourselves our immune system ensures that foreign invaders do not take over our bodies. 

The 2007 Forbeck Foundation Forum will focus on the topic of microRNA. MicroRNA, as the name implies, are small RNA that have been identified in human cells. Despite their small sizes, microRNAs have big roles in human biology. Recently, scientists have discovered that microRNAs are involved in cancer, and that microRNA will be useful in the prediction, the diagnosis and the treatment of cancer. The Forbeck Forum on MicroRNA and Cancer will be a catalyst for expanding this forefront of cancer research. 

The focus of this meeting will be on tumor stem cells; how they arise and how they differ from the progeny that originate from these stem cells. Until 1998, stem cell biology was a field of narrow interest to developmental biologists with a single point of contact to adult human medicine: bone marrow transplantation. 

The diagnosis and treatment of cancer has changed dramatically in the past two decades as advances in medical science have revealed the causes of cancer at the molecular level. This understanding has provided new targets for drug discovery, new approaches to evaluation of high-risk patients, and methods for early detection of cancer. 

This topic pertains to the new quest of utilizing molecular and genetic information about cancer to specifically design treatments which target functionally important molecular lesions. In the past several decades enormous quantities of information have accumulated regarding the precise mutations which either activate or disrupt genes in many human cancers. 

The important role that DNA damage plays in cancer development is illustrated by the clear connections between exposures to certain types of DNA damaging agents in the environment and the development of cancer, such as the links between cigarette smoking and lung cancer or sunlight exposure and skin cancer. 

The topic of the 2002 Forbeck Forum pertains to the growth abnormalities that are characteristic of all types of tumors. Normal cells have limited life spans while tumor cells acquire genetic changes that result in immortalization and infinite growth capacity. Studies in the past decade have begun to unravel the molecular mechanisms responsible for this uncontrolled growth. These studies have provided many insights into how cancers start since the genes that cause this unrestricted growth are so commonly mutated in human cancers.

We are reliant on drug therapy for the treatment of the majority of cancers that have spread throughout the body. Many of these agents have been in existence for many years and in general the drugs work by killing rapidly dividing cells within the body. This means that the drugs damage both cancer cells and normal cells in the body that are also rapidly dividing. This is why blood counts fall and hair falls out after patients receive certain types of cancer drugs. 

The Forbeck Forum 2000 relates to the high dose drug therapy, treatment so toxic that it requires a bone marrow transplant to rescue the patient’s blood system. The graft of bone marrow can come from two sources. It is possible to harvest components of the blood system directly from the patient before therapy and give it back when treatment is completed. 

Everyone has heard of gene therapy, this is going to revolutionize medicine and bring untold benefits to us all. This is the message we read in the press, but what is the truth? Has any gene therapy trial in patients with cancer produced a single response? The data is not very impressive in 1998, but a great deal of work remains and it is very early days. 

Chemotherapy is the mainstay of treating tumors which have spread throughout the body. However, all cancer drugs, while potentially benefiting the patient, cause side effects which can limit their use. Doctors continue to strive to develop new approaches to destroy cancers without damaging normal tissues. This was the topic of our 1996 Forum, but it did not address the topic of drug delivery.

Some of the drugs we use to treat cancers can cause so much damage to normal cells that secondary cancers can result later in life. We are gaining insights into which drugs are the “bad actors” and protocols are being developed to attempt to reduce the use of these agents. However, the problem is not this simple. Why does the problem only occur in some patients; who is at risk and why? What type of damage do the drugs do to cells and how does this lead to the development of new cancers? Are there options to reduce the problem and if so can they be introduced rapidly into the clinic?