Monoclonal antibody therapy is one type of biologic therapy that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion and are used to carry drugs, toxins, or radioactive material directly to the cancer cells.

Share This

After 2003, the number of new cancer cases became artificially reduced which allowed agencies like the American Cancer Society to claim that progress is being made. In 2004 the Centers for Disease Control (CDC) reported that VA hospitals in at least 13 states are no longer reporting cancer cases and that reporting has been inconsistent in 14 additional states. Therefore, as many as 70,000 new cancer cases (about 5% of the national total) were not reported. Any improvement in the number of cancer cases is therefore in doubt.

Those Great New Cancer Drugs

In 2003 and 2004, there was a lot of publicity about the “great new cancer drugs.” In March 2004, the Executive Editor of Fortune Magazine wrote an extensive article about these new drugs. The title of the article was all revealing, “Why We’re Losing the War on Cancer.” To order this article**.

Leaf reports that the two new blockbuster drugs, Avastin and Erbitux, aren’t effective. He reports that Avastin, “managed to extend the lives of some 400 patients with terminal colorectal cancer by 4.7 months” considering the possible side effects, that is not really worth the risk when there are safe effective alternative treatments available. And Leaf reported that Erbitux did even worse, “has not been shown to prolong patients’ lives at all” and it costs $2,400 a week. It is typical for the Cancer industry and mainstream media to pump up any of the new therapies. Leaf admits, Fortune magazine ran a cover article on Interleukin-2 with a “Cancer Breakthrough” headline. As any oncologist will tell you, it wasn’t.

The article goes on to report that Europe seems to have the same problems. The twelve new anticancer drugs approved in Europe between 1995 and 2000 did not improve survival or quality of life nor were they safer than the older drugs. However, they were several times more expensive. Here are some extensive statistics** regarding the progress of conventional cancer treatment from the United Kingdom.

In 2005 Herceptin was hyped as “astonishingly effective.wonder drug.” However, the truth is far different. Ralph W. Moss, Ph.D. has written a report on the Herceptin decption. Here is what Michael Janson, MD, past president of both the American College for Advancement in Medicine (ACAM) and the American Preventive Medical Association (APMA) has to say about this special report:

“Dr. Moss has once again cut through the hype of medical research and media reports with a keen, objective analysis that presents the true picture of scientific results regarding the latest ‘miracle’ in cancer therapy. He reveals the hollow core of the recent medical reports on Herceptin, showing that it is not what has been claimed, and that the statistics were manipulated to make it seem far better than it is, while underplaying the potential risks. The conflict of interest among the authors that he notes is a danger to honest researchers and to the public who might mistakenly take this drug (and many others) in inappropriate situations. Let’s hope that his analysis gets wide attention.”

Remember Lung Cancer Drug Iressa?

From a Newsday article of December 18, 2004, “Shocking the medical and financial worlds, a highly touted lung cancer drug, Iressa, failed to help patients live longer in a major clinical trial.” How can these hyped-up drugs get all the way to clinical trials? The promise of tremendous profits is the only explanation.

Why Doctors Prescribe the Newest Drugs

Doctors do not prescribe the newest drugs because they are better for you. Everyone’s body chemistry is different, a treatment that worked for some people may not work for you. Conventional doctors do nothing to determine which of the available treatments for your cancer will work for you. They just prescribe the newest pharmaceutical drug. Pharmaceutical companies love this because the newest drug is usually the most expensive. Doctors do this because:

—      They do not want to appear to be behind the times.

—      The new cancer drugs appear to be better because of the hype that accompanies their release

—      The side effects of new drugs are not well-known in the beginning.

Would you like to know what happened to good medicine?

The Wrong Attack

Cancer cells obtain their energy from fermentation. Normal cells obtain their energy from oxygenation (except muscle cells when they are completely exhausted). This is a tremendous difference. Alternative cancer treatments such as Cancell and Paw Paw target this difference. Conventional cancer research ignores this tremendous difference continues to seek methods to destroy fast growing. Our immune system contains mostly fast-growing cells. The worst thing to do when you are sick is to attack your immune system.

Conventional research seems to do everything wrong. For example, it relies heavily on animal testing. Here is an article that exposes the fallacy of using animals for medical research*.

Table of Contents | Return to the Comparison Table* | World Without Cancer

Conventional vs Alternative Effectiveness

The standard position of conventional Western medicine regarding alternative treatments such as nutrition and planned based medicine is that such treatments are not as effective as drugs. However, in an Independent (UK) article of 08 December 2003 , Allen Rosesl, a vice-president of GlaxoSmithKline(a lagre international pharmaceutical company) was quoted as saying, “most drugs work in 30 to 50 per cent of people” (who take them). This is about the same as the effectiveness range of alternative cancer treatments.

Considering Chemo?

Don’t miss the subsection below “Taxol Spreads Breast Cancer” and especially the pink text.

A study of over 10,000 patients shows clearly that chemo’s supposedly strong track record with Hodgkin’s disease (lymphoma) is actually a lie. Patients who underwent chemo were 14 times more likely to develop leukemia and 6 times more likely to develop cancers of the bones, joints, and soft tissues than those patients who did not undergo chemotherapy (NCI Journal 87:10).

Safe and effective plant based treatments cannot produce large profits because they cannot be patented. Large profits are needed to pay for the expensive FDA approved clinical trials. So plant based treatments never get FDA approved to treat a disease. Your doctor can only prescribe treatments that are FDA approved. If your doctor prescribes treatments that are not FDA approved, he or she can be sued.

From the 12th December 2002 issue of Journal of the American Medical Association, in a review with James Spencer Malpas, M.D., D.Phil. St. Bartholomew’s Hospital London, United Kingdom:

“A recent randomized trial of treatment for stage one multiple myeloma by Riccardi and colleagues (British Journal of Cancer 2000;82:1254-60) showed no advantage of conventional chemotherapy over no treatment.”

The above statement is in direct contrast to popular belief that chemo is likely to help you. The reason for this belief is statements like this:

“1998 was truly one of the most exciting years for cancer research,” said Harmon Eyre, MD, executive vice president for research and medical affairs for the American Cancer Society (ACS). “While we are closer than ever to finding answers…” followed by a pitch for more donations.

Another popular belief that is repeated in movies and TV shows is that not taking chemo is dumb or cowardice. Nothing could be further from the truth. It is the smart cancer patient who does enough research to learn the fraud of conventional cancer treatment and only the brave who stand up against the pressures of oncologists.

Share This

Although recently developed drugs have made many cancers survivable, multiple myeloma has resisted scientists’ best efforts. The likelihood of a patient withstanding this blood-cell cancer for 5 years remains less than 1 in 3–as it has been for 3 decades.

Now, the notorious antinausea drug thalidomide is demonstrating power that outclasses standard chemotherapy against myeloma. Banned in the 1960s for causing birth defects, thalidomide more recently has been shown to cure mouth ulcers and relieve complications of leprosy (SN: 11/11/95, p. 311; SN: 8/15/98, p. 111).

Thalidomide prescribed in gradually increasing doses brought about improvements in 27 of 84 multiple myeloma patients in whom standard treatments had failed, scientists report in the Nov. 18 NEW ENGLAND JOURNAL OF MEDICINE.

The researchers at the University of Arkansas for Medical Sciences in Little Rock tracked the effects of thalidomide for a year by testing patients’ blood and urine monthly for unusual proteins associated with the myeloma. After the year, 2 of the 84 patients were free of these proteins, indicating the cancer was in complete remission.

Six others showed declines in the proteins to less than a 10th of the abnormally high concentrations seen after the patients failed chemotherapy. In 19 others, the concentrations fell at times to less than three-quarters of what they had been, says coauthor Seema Singhal, an oncologist now at the University of South Carolina Cancer Center in Columbia.

Share This

The disease is considered incurable, and conventional therapy results in complete remission in only 5% of patients with overall median survival only about 36 months. Recent clinical trials are offering new hope, though, indicating complete remission rates of 25-30% with median survival exceeding 5 years achieved with a more aggressive approach utilizing higher doses of drugs and stem cell transplants.

“Standard therapies for multiple myeloma really hadn’t improved up until a few years ago, when thalidomide became available,” said David H. Vesole, MD, PhD, FACP, Medical College of Wisconsin Professor of Medicine. “Now we’ve got a couple of targeted chemotherapies that can improve the outcome of the disease and increase survival.

“Increasing survival translates into better quality of life for most of these patients. The usual treatment is to start off with some initial therapy that’s up to the individual doctor. There are a couple of different ‘recipes’ for initial therapy. The one that’s gotten a lot of favor lately, even though it hasn’t yet been proved to be superior in randomized trials, is the use of the drug thalidomide and some kind of steroid. We’ve already done one study with thalidomide and the steroid dexamethasone, and there are other studies going on.”

There are more than 14,600 current cases of multiple myeloma in the US, Dr. Vesole said, representing 1% of all malignancies and 10% of all blood-borne malignancies. For unknown reasons, the incidence of this cancer is twice as high among African-Americans.

High Protein Levels an Indicator

“The myeloma cancer cells themselves don’t actually eat up bone,” said Dr. Vesole. “Cells in our bones form bone and break down bone. We all have that. The way I explain it to patients is that there’s a ‘phone system’ in the myeloma cells that tells the ‘Pac-Man’ cells to eat bone uncontrollably.

“These ‘Pac-Man’ cells, which are called osteoclasts, have voracious appetites. They just hold on and chomp up bone and make holes. It’s as if you can sneeze on someone with this and break all their bones. So, you get bad bone lesions. Most commonly it’s in the back that you get pressure fractures, because of gravity. Patients can get holes in the skull from this disease.”

The most common signs of multiple myeloma, Dr. Vesole said, are anemia or fatigue and painful bone lesions because the bones are already broken or about to be broken. (The “multiple” in multiple myeloma refers to the fact that multiple bones in different parts of the body are involved).

“In some patients the condition gets picked up during routine blood tests,” Dr. Vesole said. “Normal plasma cells make antibodies to infections. Another thing associated with this disease is that these people make antibody-like proteins but there’s no infection, so the levels of the proteins go up. Sometimes incidentally they’ll go to the doctor’s office and find out their proteins are sky-high. Another test can discover a big spike of protein that the patient shouldn’t have, and that’s the monochromal or myeloma protein.”

A Highly Resistant Disease

Multiple myeloma has been very resistant to treatment since the major clinical features of the disease were first described in England around 1850. But recently, as one of several articles on the topic authored or co-authored by Dr. Vesole stated, “tremendous advances have been made in understanding the biology and developing treatments of multiple myeloma.”

“This is a very slow-growing disease,” Dr. Vesole said. “We think that the initial event happens ten to fifteen years before there’s any clinical evidence of it in a patient. These cells often have very complex chromosome abnormalities that evolve over time. They continue to become more and more malignant over time. Many cancers eventually become resistant. In myeloma cells, they’re resistant from the day they walk in the door even though they haven’t been exposed to any chemotherapy.

“The best way I can explain that to a patient is to say ‘if you have an individual who has acute leukemia, and they walk in the door at age 55 and we give them leukemia drugs, the chance of getting complete remission is probably 75-80%. If you walk in the door with myeloma, and we give you myeloma drugs, the chance of remission is only 5% because the cells are already resistant to the drugs.’”

It wasn’t until the mid-1980s that studies showed stronger doses could help overcome multiple myeloma’s inherent resistance to drug therapy, Dr. Vesole said. “We asked if more drugs could pulverize more of these cells, and the answer was ‘yes.’

And we have drugs that we didn’t have then. Thalidomide is now available (although it is not yet formally approved and is in effect used “off label” for multiple myeloma treatment). A new drug that was just approved, called Velcade, has a completely different mechanism from any other drug - it’s an entirely new drug class.”

Stem Cell Transplants Could Lead to Cure

The relative ineffectiveness of older drug therapies helped spur research into stem cell transplants for multiple myeloma, which are now regularly performed, Dr. Vesole said. He is one of the principal investigators in an ongoing National Institutes of Health national trial looking at new “tandem” stem cell transplants.

Instead of a single bone marrow cell transplant to obliterate cancerous cells, the tandem approach uses two transplants in sequence. The first transplant is designed to destroy most of the cancer. The second, performed three to six months later, is directed at “straggling” cancer cells.

The NIH trial is comparing outcomes between two “autologous” transplants, both using the patient’s own cells, and another tandem method using the patient’s cells first followed by a transplant of cells from another donor. A third approach being studied at the Medical College uses high doses of drugs first, followed by one stem cell transplant from a donor other than the patient so that the donor’s immune system can be a source of immune therapy to get rid of any remaining cancer.

“By doing donor transplants, multiple myeloma might be curable,” said Dr. Vesole. “The first reason why we don’t cure it using just the patient’s own cells is that we know we give them back myeloma cells and there’s no way they’re going to clean up the cells they collect. We’ve tried and it doesn’t work.

“The second thing is that some of their cells, even if you give them two different transplants, are either resistant or they’re ‘asleep’ and you don’t kill them and they eventually grow. So if you use a donor you don’t have to worry about giving back cancer cells and a donor immune system can perceive resistant or sleeping cells and still kill them.”

Share This

Division of Oncology Drug Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Rockville, Maryland, USA

Robert C. Kane, M.D., F.A.C.P., U.S. FDA, HFD-150, 5600 Fishers Lane, Rockville, Maryland 20857, USA. Telephone: 301-594-2473; Fax: 301-594-0499; e-mail kaner@cder.fda.gov

Bortezomib (formerly PS-341), a promising new drug for the treatment of multiple myeloma, recently received accelerated approval from the U.S. Food and Drug Administration (FDA) for the therapy of patients with progressive myeloma after previous treatment. Two phase II studies of bortezomib used the same schedule of twice-weekly i.v. dosing for the first 2 weeks of each 3-week cycle. In a randomized study of 54 patients, two doses were compared (1.0 and 1.3 mg/m²) and objective responses occurred at both dose levels (23% versus 35%), including one complete response in each arm. In the other phase II study, 202 heavily pretreated patients (median of six prior therapies) all received the same schedule at 1.3 mg/m². Of 188 evaluable patients, complete responses occurred in five (3%) and partial responses occurred in 47 (25%). The median duration of response was 365 days. The most clinically relevant adverse events were asthenic conditions, nausea, vomiting, diarrhea, thrombocytopenia, and a peripheral neuropathy that often was painful. This report highlights the FDA analysis supporting the accelerated approval.

Key Words. Multiple myeloma • Bortezomib • Velcade^® • Accelerated approval

Share This

SDX-101, the etodolac R-enantiomer, is an anti-inflammatory drug with a cytotoxic effect on multiple myeloma cells but not on normal peripheral blood mononuclear cells.

The antiproliferative activity of nonsteroidal anti-inflammatory drugs and their potential use as antitumor agents are under scrutiny.¹ A starting point is the demonstration that these drugs have some effects on cancer cells.

In this issue of Blood, Yasui and colleagues provide the first evidence of the cytotoxic effect of SDX-101, the R-enantiomer of etodolac, in different multiple myeloma (MM) cell lines. The authors illustrate SDX-101’s antitumor activity against both drug-sensitive and -resistant MM cells and against primary patient MM cells within the bone marrow environment. It is important to bear in mind that these effects were obtained with concentrations without cytotoxicity on normal peripheral blood mononuclear cells and at clinically achievable plasma levels.

Some MM cells were resistant to doxorubicin, dexamethasone, and bortezomib and were hence highly hypermutated. The cytotoxic effect is mediated via caspase-8/-9/-3 activation and apoptosis. In addition, SDX-101 induced down-regulation of cyclin D1 expression in MM cells, resulting in an apoptotic population, as shown by cell-cycle analysis.

As they have previously shown that novel chemotherapeutic agents augment the cytotoxicity of dexamethasone,² Yasui and colleagues now demonstrate that the combination of SDX-101 plus dexamethasone is highly synergistic. It has been well established that myeloid cell leukemia-1 (Mcl-1) plays an important role in proliferation and inhibition of apoptosis, as well as in the induction of drug resistance³: the results obtained by Yasui and colleagues thus strongly suggest that up-regulation of the proapoptotic variant Mcl-1_S and inhibition of the antiapoptotic variant Mcl-1_L are the principal events in the apoptotic activity of SDX-101.

It has previously been reported that the bone marrow microenvironment plays an important role in the pathogenesis of MM.^4,5 Yasui and colleagues demonstrate that SDX-101 ablates the growth stimulatory effect of this microenvironment on MM cells. It is interesting to note that SDX-101 lacks cyclooxygenase(COX) inhibitory activity and hence the related side effects and that it is approved for treatment of degenerative joint diseases and rheumatoid arthritis. Results as a whole provide the preclinical framework for clinical trials of SDX-101 alone or in combination with dexamethasone to improve patient outcome in MM. The study is an important contribution to MM research.

Share This

Multiple myeloma is a malignant proliferation of plasma cells that involves more than 10 percent of the bone marrow. It is a prototype primary malignancy of the bone associated with malignant plasma cells that secrete monoclonal immunoglobulins into the serum, the urine or both.

Multiple myeloma is the most common primary cancer of the bones in adults. The annual incidence in the United States is three to four cases per 100,000 population. Multiple myeloma represents 1 percent of all cancers diagnosed in the United States and 10 percent of all hematologic malignancies. The median age at diagnosis of multiple myeloma is 62 years. Only 2 to 3 percent of cases are reported in patients younger than 30 years.2

The disease is called multiple myeloma because myeloma cells can occur in multiple bone marrow sites in your body. If you have multiple myeloma but aren’t experiencing symptoms, your doctors may just need to monitor your condition. If you’re experiencing symptoms, a variety of treatments are available.

Blacks in the United States are twice as likely to suffer from multiple myeloma as whites. In fact, multiple myeloma is the most common hematologic malignancy in the U.S. black population.3 Multiple myeloma is rare among persons of Asian descent, with an incidence of only one to two cases per 100,000 population. Standard therapy for multiple myeloma includes alkylating agents administered with prednisone. The most commonly used alkylating agent is melphalan (Alkeran). Melphalan, 9 mg per m2, is given orally with 100 mg of prednisone on days 1 through 4. Courses of therapy are repeated at four- to six-week intervals for at least one year.

Share This

antibody studies

Plasma cell tumours (myelomas) have made it possible to study individual antibodies since these tumours, which are descendants of a single plasma cell, produce one antibody in abundance. Another method of obtaining large amounts of a specific antibody is by fusing a B lymphocyte with a rapidly growing cancer cell. The resultant hybrid cell, known as a hybridoma, multiplies rapidly in culture….

blood diseases

Another malignant disease, probably related to the above conditions, is multiple myeloma, which is characterized by a malignant overgrowth of plasma cells within the bone marrow. This severely painful disorder causes defects in the bone of the skull, the ribs, the spine, and the pelvis that ultimately result in fractures. As the bone marrow becomes more involved, anemia develops and hemorrhages…

cancers of the lymphocytes

…most prevalent of the childhood leukemias. Similarly, most cases of Hodgkin disease, a common type of lymphoma that mainly strikes adults, can be cured by drugs, radiation, or a combination of both. Myelomas primarily arise in older individuals. These tumours grow fairly slowly and are usually diagnosed by virtue of the characteristic immunoglobulin they secrete, which may be produced in such…

monoclonal antibody production

An astonishingly high serum concentration of a single type of immunoglobulin is associated with multiple myeloma, a type of cancer in which a single B cell proliferates to form a tumorous clone of antibody-secreting cells that can multiply indefinitely, like all cancer cells (see immune system disorder: Cancers of the lymphocytes). Thus the immunoglobulins made by myelomas are monoclonal, and…

thalidomide

More recent studies suggest that thalidomide may have activity against multiple myeloma, a variety of solid tumours, and other hematologic cancers. In addition to its ability to inhibit production of TNF, it appears that thalidomide may inhibit production of other immunoregulatory substances and may inhibit the growth of new blood vessels (angiogenesis), possibly by blocking growth factors that…

Magazine and Journal Articles :

Taking on a lethal blood cancer.

By: Seppa, Nathan. Science News, 1/1/2005, Vol. 167 Issue 1, p14-14 This article focuses on a new drug, bortezomib, that helps fight mantle-cell lymphoma. From San Diego, at a meeting of the American Society of Hematology. Non-Hodgkin’s lymphoma is mainly a malignancy of antibody-making immune cells called B lymphocytes. While drugs have helped many patients fend off some forms of this cancer, an aggressive form known as mantle-cell lymphoma often recurs after chemotherapy. This lymphoma arises from B cells that form a mantle around the inner core of lymph nodes. Researchers now report that a drug called bortezomib, already approved for use against the bone marrow cancer multiple myeloma, helped patients with mantle-cell lymphoma who had failed to improve on three previous treatment regimens. Reading Level (Lexile): 1310;

WEEK IN REVIEW.

Crain’s Detroit Business, 4/11/2005, Vol. 21 Issue 15, p26-26 This article reports that two law firms have filed suits seeking class-action status for shareholders of Collins & Aikman Corp. in U.S. District Court. Troy-based Collins & Aikman said last month that it likely would have to restate earnings from last year because of improper accounting of vendor rebates. The Auburn Hills City Council tabled discussion until April 18 on a proposed 60,000-square-foot expansion of The Palace of Auburn Hills, the Detroit Free Press reported. Champion Enterprises Inc. has sold 22 retail centers in six deals worth $20 million, part of the manufactured-home producer’s plan to exit retail. Reading Level (Lexile): 1200;

WEEK IN REVIEW.

Crain’s Detroit Business, 4/18/2005, Vol. 21 Issue 16, p34-34 The article presents news related to the week of April 9-15, 2005. The Michigan Gaming Control Board has approved the sale of Mandalay Resort Group Inc.’s 53.5 per cent share of MotorCity Casino LLC to Marian Ilitch, who already owns 25 percent interest in the casino. In another case, Detroit, Michigan, needs voter approval of a new 2 per cent sales tax on fast food and a property-transfer tax, plus more than 750 layoffs and 10 per cent pay cuts through days off without pay, to balance the $1.4 billion 2005-2006 budget, Mayor Kwame Kilpatrick said. Reading Level (Lexile): 1200;

First American CFO Klemens Dies at 55.

By: Shenn, Jody. American Banker, 1/6/2006, Vol. 171 Issue 4, p9-9 This article presents an obituary for Thomas A. Klemens, the longtime chief financial officer of the Santa Ana, Calif., title, settlement service, and real estate data company First American Corp. Reading Level (Lexile): 1250;

Managing cancer.

By: Marshall, Samantha. Crain’s New York Business, 4/17/2006, Vol. 22 Issue 16, p35-36
The article reports that targeted therapy, genetic-based treatments, sophisticated radiation and better surgical techniques are lengthening lives and new medicines to manage side effects and pain are making it possible for many cancer patients to handle a full work schedule. Subsequent research shows that the vast majority of patients at all stages return to their jobs and are as productive as their co-workers. Federal laws like the Americans with Disabilities Act and the Family Medical Leave Act protect workers with cancer from being fired and compel employers to be flexible about time off for treatment. Reading Level (Lexile): 1240;

WEEK IN REVIEW.

Crain’s Detroit Business, 5/15/2006, Vol. 22 Issue 20, p34-34 This article presents information on several business developments in Michigan. Novi-based ITC Holdings Corp. is acquiring Michigan’s other major electricity-transmission company, Michigan Electric Transmission Co. in an $866 million deal. The acquisition will give ITC, whose 150-employee subsidiary ITCTransmission operates Southeast Michigan’s system, ownership of METC’s electricity-transmission system in the western Lower Peninsula. Roger Penske was elected chairman of the Downtown Detroit Partnership on Monday morning and announced that he will seek private-sector funding for a downtown cleanup initiative to be led by him and Mayor Kwame Kilpatrick. Called Next Detroit: Clean Downtown, the campaign has a budget of $1.2 million for the rest of this year and $1.5 million for next year. Reading Level (Lexile): 1250;

Share This

Keywords: MULTIPLE MYELOMA; FAMILIAL INCIDENCE OF TUMORS; P53

Document Type: Short communication

DOI: 10.1163/15685590151092698

Affiliations: 1: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary 2: Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary 3: Division of Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg, Germany 4: 1st Department of Internal Medicine, Semmelweis University, Budapest 5: 3rd Department of Internal Medicine, St. Stephan Hospital, Budapest

Share This

Introduction

MM is a haematologic cancer arising from a common progenitor of the B-cell lineage. It is characterised by a clonal expansion of plasma cells in the bone marrow (BM) and is nearly always accompanied by the presence of a monoclonal immunoglobulin (Ig) or Ig fragment in the serum and/or urine of patients.1,2 It is the second most common haematologic malignancy, and is responsible for at least 2% of cancer-related deaths. In 2006, an estimated 16,570 new cases of MM will be diagnosed in the US, and 11,310 deaths will be attributed to this disease.3 The last several years have seen the introduction of a number of novel agents in the treatment of this otherwise incurable cancer. Important advances, including drugs such as thalidomide (Thal), lenalidomide, and bortezomib, have provided effective therapeutic options for patients with MM.4 These and other novel agents hold promise to translate MM into a chronic disease.

Identification and Validation of Novel MM Therapies

In order to overcome resistance to conventional therapies and improve patient outcome, novel treatment approaches that target mechanisms whereby MM cells grow and survive in both the BM and extramedullary microenvironment are needed.

Our in vitro and animal model studies have demonstrated the importance of the BM microenvironment in promoting MM cell growth, survival, drug resistance and migration. These model systems have allowed for the development of several promising biologically based therapies that can target the MM cell in its BM microenvironment and thereby overcome classic drug resistance in vitro, including Thal and its more potent immunomodulatory analog, lenalidomide, as well as the proteasome inhibitor bortezomib.4 Once in vitro promise of these novel agents was demonstrated, efficacy was tested in murine models. Importantly, these laboratory studies have been translated to phase I, II, and III trials to evaluate their clinical efficacy and toxicity. In this context, bortezomib was FDAapproved for the treatment of relapsed and/or refractory MM;5 and both Thal and lenalidomide are currently being considered for approval by the agency. Several other classes of novel biologics, including histone deacetylase inhibitors, heat shock protein inhibitors, mTOR inhibitors, cyclin d inhibitors, pAKT inhibitors and oral proteasome inhibitors, among others are undergoing preclinical and clinical evaluation.These preclinical studies have informed the use of rational combination treatments in ongoing clinical trials.

Share This