Drug found that significantly slows growth of most aggressive form of breast cancer
13 JUNE 2016 • 4:23PM
Scientists have found a method of significantly slowing the growth of the most aggressive form of breast cancer.
Researchers at Oxford and Nottingham Universities used a new drug to attack the disease in deeper regions of cancer tumours than conventional therapies like chemotherapy or radiotherapy are often able to reach.
JQ1, which was trialled on human cancer tumours grown in mice, works by altering the way cancer cells respond to hypoxia – or low oxygen – a feature most commonly found in triple negative cancer, the form of the disease hardest to treat.
"It was really quite a good result, I do feel it could mean added benefits for patients" Dr Alan McIntyre, University of Nottingham
The scientists found the drug was able to slow the growth of cancerous tumours by roughly a third each day.
They predict that, when combined with chemotherapy and radiotherapy, the drug could bring “added benefits” to patients with a triple negative variation, which make up about 15 percent of the roughly 50,000 women diagnosed with breast cancer each year.
Breast cancers that are starved of oxygen, such as the triple negative form, are difficult to treat because the cancer cells adapt to hypoxia in ways that make them resistant to standard therapies.
Low oxygen levels prompt tumour cells to turn on specific genes which send signals for new blood vessels to supply them with fresh oxygen, giving cancer the nutrients it needs to grow.
JQ1, one of a class of drugs known as BET inhibitors, tackles this process at a molecular level.
About Breast cancer Signs and symptoms of breast cancer: A change in size or shape of the breast A lump or thickening that feels different from the rest of the breast tissue Redness or a rash on the skin and/or around the nipple A change in skin texture such as puckering or dimpling Discharge (liquid) that comes from the nipple without squeezing Nipple becoming inverted or changing its position or shape A swelling in the armpit or around the collarbone Constant pain in the breast or armpit What to do if you find a change: Most changes are likely to be normal or due to a benign (not cancer) breast condition If you notice a change, visit a GP as soon as possible A GP may feel there is no need for further investigation or may refer you to a breast clinic If you do not feel comfortable with a male GP, ask if there is a female GP available Source: Breast Cancer Care
Dr Alan McIntyre, co-author of the study, which is published in the journal Oncogene, said: “Triple negative breast cancer is a challenge.
“By tackling hypoxia that so often compromises the treatment of breast cancers, JQ1 could be an important key to helping women with aggressive breast tumours.
“It was really quite a good result, particularly as we were just using this drug and not any others.
“I do feel it could mean added benefits for patients.”
Triple negative breast cancer is so called because it lacks receptors for oestrogen, progesterone and the HER2 protein, which the most successful treatment use to target the disease.
However, tipple negative cancer is typically responsive to chemotherapy.
Dr McIntyre, from the University of Nottingham, said JQ1 was currently being used in clinical trials investigating other cancers and that he expected analysis of those results to show the drug has been benefiting human subjects in the trials.
Spokesman for Cancer Research UK, which provided funding for the new research, said: “This study has unearthed insights into how these drugs could be used to help treat triple negative breast cancer patients who urgently need better treatments.
“Interfering with the with the body’s natural response to hypoxia, or low oxygen, could be a way to stop the spread of the cancer.
“More studies should be carried out to measure how effective JQ1 could be in patients.”
MultiCell Immunotherapeutics And Oxis Biotech Sign Antibody-Drug Conjugate R&D, Product License And Commercialization Agreement
WOONSOCKET, R.I., March 12, 2015 /PRNewswire/ -- MultiCell Immunotherapeutics, Inc. (MCIT), a majority owned subsidiary of MultiCell Technologies, Inc. (OTC: MCET) announced today it has signed a research & development and product license agreement with Oxis Biotech, Inc. (OXIS) to create three novel antibody-drug conjugates (ADCs) containing OXIS' lead drug candidates using MCIT's proprietary ADC platform technology. These ADC product candidates are to be used by OXIS for the treatment of triple-negative breast cancer, and multiple myeloma and associated osteolytic lesions which are significant unmet medical needs.
Under the terms of the agreement, OXIS paid MCIT a license fee of $500,000, and will reimburse MCIT up to $1.125 million in development costs for the three ADC product candidates. Oxis will also pay up to $12.75 million in clinical development milestones, and was granted an option to purchase manufacturing rights to the three ADCs upon payment of an additional $10 million. OXIS was also granted a worldwide exclusive license to sell the three ADC product candidates, and will pay a royalty of 3% of net yearly sales. MCIT retained all rights to its ADC platform for all therapeutic indications, and is free to pursue its own drug development programs and to partner with other interested pharmaceutical and biotechnology companies.
Sales of breast cancer drugs are projected to increase in nine major world markets from $9.8 billion in 2013 to $18.2 billion by 2023, according to new forecasts from IMS Health. Analysts at Visiongain, Ltd. predict the world market for multiple myeloma therapies will reach $11.5 billion in 2017.
According to FiercePharma, Celgene's cancer drug Revlimid® for the treatment of multiple myeloma generated nearly $5 billion in revenue for the company in 2014. Analysts believe sales of Revlimid could double within 5 years as a result of FDA's recent approval of expanded labeling concerning the use of Revlimid in combination with dexamethasone for patients newly diagnosed with multiple myeloma. About 93,600 patients are living with multiple myeloma in Europe and about 88,499 patients are living with it in the United States, Celgene said.
PDL BioPharma, Inc. stated its licensee Genentech, Inc. reported sales of Herceptin® which is used to treat HER2 breast cancer totaled $7.3 billion in 2014. Of the 280,000 patients in the USA diagnosed annually with breast cancer, about 20% are diagnosed with triple-negative breast cancer. Treatment options for triple-negative breast cancer patients are limited because the three most common types of receptors known to fuel most breast cancer growth – estrogen, progesterone, and the HER-2/neu gene – are not present in the triple-negative breast cancer cells, hence patients are ineligible for treatment with either hormonal or HER2-targeted agents such as Herceptin. Treatment typically involves non-targeted cytotoxic chemotherapies.
The Emmes Group, a strategy consulting firm with offices in Boston and San Francisco, believes if OXIS achieves all of its clinical development milestones, purchases manufacturing rights to the ADCs, and meets worldwide sales and sublicensing expectations following receipt of marketing approval for the three ADCs for the treatment of breast cancer and multiple myeloma, MCIT could expect to receive in excess of $540 million during the term of the agreement.
MCIT's ADC platform technology is based on unique multivalent, cleavable linkers that allow tethered drugs to be released intracellularly or extracellularly upon binding of the antibody to the target cell. Additionally, the MCIT linkers are designed to attach multiple drugs per targeting antibody, and to release the drugs in their original form without modification of the drug.
"We are very excited about our novel, enabling antibody-drug conjugate technology, and are pleased to partner with Oxis Biotech to develop targeted delivery versions of their drug candidates", said W. Gerald Newmin, Chairman and Chief Executive Officer of MultiCell Immunotherapeutics. "We continue to explore therapeutic indications and drug combinations of interest to us, and will continue to aggressively seek partnerships with larger pharmaceutical and biotechnology companies who are interested in using our ADC technology to help facilitate the targeted delivery of their drugs," stated Mr. Newmin.
OXS-2175 is a small molecule therapeutic candidate that has shown promise in early-stage preclinical in vitro and in vivo models of triple-negative breast cancer. We are investigating OXS-2175 formulated as an infusible therapy and as part of an ADC infusible therapy for the treatment of triple-negative breast cancer.
MARKET NEED — TRIPLE-NEGATIVE BREAST CANCER
According to the American Cancer Society there were approximately 231,840 new cases of invasive breast cancer last year in the USA and 40,290 deaths from breast cancer during the same period. Women represent 99% of all breast cancer patients. Breast cancer is treated by various combinations of surgery, radiation therapy, chemotherapy, and hormone therapy. TNBC is a type of breast cancer characterized by breast cancer cells that do not express estrogen receptors, progesterone receptors, or large amounts of HER2/neu protein. Approximately 10% - 20% percent of invasive breast cancers are diagnosed as triple-negative breast cancers. TNBC is more likely to affect younger people, African Americans or Hispanics, and those with a BRCA1 gene mutation. TNBC is insensitive to many of the most effective therapies available for the treatment of breast cancer including the HER2-directed therapy Herceptin® (trastuzumab), and endocrine therapies such as tamoxifen or the aromatase inhibitors. The relapse and survival rates of TNBC patients are shorter than for patients with other types of breast cancer. There is no current or pending drug therapy available for the treatment of TNBC.
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