Category: Research

New Research from Weill Cornell Medicine (WCM) Sheds Light on the Prevalence of Heart Attack and Stroke in Diagnosed Cancer Patients

Cancer cells produce substances that “thicken” the blood, so men and women with cancer have a significantly higher risk of developing blood clots. A manifestation of blood clots can be cardiovascular events such as heart attack and stroke. The latest research found that six months after diagnosis, people with cancer had a higher rate of heart attack or stroke.

New research from Weill Cornell Medicine (WCM), published in the Journal of the American College of Cardiology, found that patients newly diagnosed with cancer are more than twice as likely to suffer from arterial thromboembolism – a sudden interruption of blood flow to an organ or body part due to a clot that has come from another part of the body – as cancer-free patients. The types of cancers studied include breast, lung, prostate, colorectal, bladder, pancreatic and gastric cancer.

Dr. Babak B. Navi, neurologist at Weill Cornell Medicine, and his team evaluated the risk of heart attack and stroke in patients age 66 or older with new cancer diagnoses compared with people who did not have cancer. Results showed that six months after diagnosis, people with cancer had a higher rate of heart attack or stroke (4.7%) due to blood clots than people without cancer (2.2%). After the first six months, the differences in risk got smaller. One year after diagnosis, the risks were about the same in people with and without cancer. Dr. Babak Navi and his team also discovered that more advanced stages of cancer were associated with higher risk.

This research is an outgrowth of the data that Dr. Babak Navi presented at last year’s International Conference on Thrombosis and Hemostasis Issues in Cancer (ICTHIC)  about the risk of heart attacks and stroke in women with breast cancer. Results showed that women diagnosed with breast cancer have a higher risk of a heart attack or stroke in the first year after diagnosis compared to similar women without breast cancer.

Through the latest research, we now know the risk of clotting goes beyond breast cancer and is a risk factor for many different forms of cancer. Further research is needed in order to develop optimal strategies to prevent arterial thromboembolism in patients with cancer.

Weill Cornell Medicine

“People with cancer are known to be at increased risk of blood clots and this risk is believed to vary according to cancer type, stage of disease, and treatment modality. We also know that patients with cancer are more likely to have cardiovascular events which may be induced by tumor or its treatment,” says Dr. Scott Tagawa, medical oncologist and Director of the Weill Cornell Medicine Genitourinary (GU) Oncology Program. “This research further underscores the need to conduct clinical trials to determine the best prevention methods and treatment of thrombosis in patients with cancer.”

Mark your calendars to learn more about the cancer clotting connection at this year’s World Thrombosis Day event.

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AACR 2017: PSMA Update

Jaspreet Batra_AACR 2017_PSMA
Jaspreet Batra presents this research at AACR 2017

At the 2017 Annual Meeting for the Annual Association for Cancer Research (AACR), we presented research highlighting how we’re targeting PSMA – a marker on the surface of most prostate cancer cells – with radioimmunotherapy to kill cancer cells.

Radioimmunotherapy involves attaching radioactive particles to targeted immunotherapies that go directly to the cancer cells. The monoclonal antibody we use is called J591 and will bind only to PSMA. In this research, we attached the radioactive isotope actinium-225 (225Ac) to J591. We have used J591 linked with lutetium 177 (177Lu) and yttrium 90 (90Y) to treat patients in many clinical trials in the past. We believe that since 225Ac is an alpha particle emitter with much greater energy released that each individual antibody will lead to more tumor cell death. In our experimental models presented at the 2017 AACR meeting, 225Ac-J591 was not significantly more toxic than control (similar to placebo) in mice without tumors. When we treated mice with prostate cancer tumors, there was significant tumor killing following a single injection of 225Ac-J591.

Given our long history of administering radiolabeled J591 to hundreds of men in different clinical trials, we have plans to launch a phase I dose-escalation clinical trial (to determine safe doses and later look at tumor response) later this year. We and others are quite enthusiastic about this approach.

Using Alpha and Beta Radioisotopes to Kill Cancer Cells

Radionuclides, also known as radioisotopes, are particles that emit energy. The different particles they emit vary and some types emit damaging radiation (also called ionizing particles). This is a good thing when we’re using radiation as a way to kill cancer cells. The two main categories of radiation particles used to kill cancer cells are alpha and beta particles.

Several radioisotopes – using both alpha and beta particles — have been approved by the Food and Drug Administration (FDA) for clinical use in cancer treatment. Historically, bone-seeking radioisotopes were used for patients with painful tumors in the bone. For example, Strontium-89 (Metastron) and samarium-153 (Quadramet) are beta-emitters that are taken up like calcium into bone and were approved to decrease pain. More recently, the alpha-emitting agent radium-223 (Xofigo) was approved for men with metastatic castration-resistant disease that has spread to the bone. However, unlike the previous beta-emitting agents, radium-223 was FDA-approved because it leads to longer overall survival rather than just symptom relief. Radium-223 is an alpha particle that mimics calcium and is delivered and taken up by the bone cells. This generally occurs near tumor cells, and while we don’t know the exact mechanism of action, we suspect that in addition to being in close proximity to some tumor cells, this creates a less hospitable environment for the tumor cells that have spread to the bone.

Additionally, we can now utilize different targeting agents to take radionuclides directly to the tumor cells. Radioimmunotherapy or radioligand therapy involves the practice of attaching a radioactive isotope to a cancer-targeting antibody or small molecule that binds only to a specific cancer-related molecule on a tumor cell. This is similar to a “lock and key” scenario, where the antibody or molecule resembles the key that will only recognize a very specific lock (the cancer-related molecule).

As it turns out, essentially all prostate cancer cells have a specific “lock” called prostate-specific membrane antigen (PSMA). This lock sits on the surface of each prostate cancer cell. We have engineered very specific monoclonal antibodies and molecules that will bind only to PSMA, leading to the opportunity for “molecularly targeted” (radio-)therapy.

In terms of attaching the radioactive isotopes, we can use both alpha and beta particles depending on the location and size of the tumor.Alpha vs beta radiationAlpha particles have the advantage of a very high amount of energy and a short path length. The amount of energy is high enough so that only a small number (1-10) of alpha particles lead to lethal damage to cells. An advantage of the short path length is that only the cells in close proximity to the alpha particle are destroyed, sparing other healthy and normal tissues. However, because of the short path length travelled, the alpha particle needs to be delivered into or right next to the tumor cell. In fact, even a piece of paper (or skin) is enough to block an alpha particle. Other alpha particles are being developed to be delivered as lethal payloads when attached to carrier molecules. One of these, actinium-225 (225Ac) is an alpha-emitting radionuclide that emits 4 alpha particles. In humans the 225Ac particle has been used as part of a compound linked to an antibody to treat leukemia and it also has been linked to a PSMA-recognizing peptide to treat men with late-stage prostate cancer with initial examples published last year.

Beta particles emit a lower energy, but can travel further distances. Because of their lower energy levels, more particles are required to cause lethal damage to cells.

This video provides a great overview of the process:

Additional research is needed to decipher the best radionuclides to use for which diseases in which clinical situations. We at Weill Cornell Medicine and NewYork-Presbyterian Hospital will have both alpha and beta radionuclides linked to PSMA compounds available in the clinic this year, initially with a clinical trial using 177Lu-PSMA-617, to be followed by 225Ac-J591, then the combination of 177Lu-J591 and 177Lu-PSMA-617.