Imagining the Impossible – Curing Melanoma

Additional Info

• Audio File: hadassah/hd001.mp3
• Doctors: Lotem, Michal
• Featured Speaker: Michal Lotem, MD
• Specialty: Head of the Center for Melanoma and Cancer Immunotherapy at the Sharett Institute of Oncology, Hadassah Medical Organization
• Guest Bio: Michal Lotem, MD, is the Head of the Center for Melanoma and Cancer Immunotherapy at the Sharett Institute of Oncology of the Hadassah Medical Organization in Jerusalem, Israel.
  
  Learn more about Michal Lotem, MD
• Transcription: Melanie Cole (Host): Melanoma is the most dangerous form of skin cancer. It occurs when there is damage to the DNA that controls cell growth. And it is most often caused from sunshine or tanning salons. While melanoma is the 19th most common cancer worldwide; its rates are higher in countries with sizeable fair skinned populations including Israel, where it is among the ten most common cancers. In the US, the rates of melanoma have been rising for the last 30 years. In 2017, it is estimated that there will be up to 87,000 new cases of melanoma in the United States and up to 9.000 deaths from the disease. Here to speak with us today about melanoma is Dr. Michal Lotem. She is the head of the Center for Melanoma and Cancer Immunotherapy at the Sharett Institute of Oncology of the Hadassah Medical Organization in Jerusalem Israel. Welcome to the show Dr. Lotem. What is melanoma? How is it different than normal skin cancer and why is it so deadly?
  
  Dr. Michal Lotem, MD (Guest): So, Melanoma is a skin cancer that starts with the normal pigment producing cells of the skin and we need these cells in the normal situation to induce tanning. Tanning gives our protection from the sun, from the ultraviolet rays of the sun. And those melanocytes which are our protectants can transform into a malignancy and the name of the malignancy is melanoma which is quite – in the sense that most situations this is the black or brownish type of a skin lesion and so for this reason, it is not too difficult to diagnose as long as there is suspicion. And why is it deadly? This is a good question. And not always do we know why a certain malignancy would be more aggressive than others and maybe it is because after years and years of exposure to ultraviolet rays, then the melanocytes gain many, many mutations. The mutations are defects in the DNA control that add and add and accumulate and endow the cancer with more aggressive traits and features.
  
  Melanie: So, how is it identified? When should you go to the doctor to find out if something might be melanoma? Would we spot this on ourselves, Dr. Lotem?
  
  Dr. Lotem: Part of the public education is to identify moles but it is quite difficult and I think the thing we must be very much aware of is the changing mole. A change is something that should attract our attention. In situations that we have many spots on the skin, some of them from the sun, some of them are completely benign tumors. In these situations, it is always very helpful to have a specialist do a skin examination. Dermatologists are helped by dermoscopy. Dermoscopy is a magnifying device that helps dermatologists see all of the tiny details and diagnose melanoma. I would recommend that any person should have his or her skin checked at least once a year and if the dermatologist then says this is a problematic skin then do it twice and even three times a year. Because it can never be too much.
  
  Melanie: That’s great advice and so if somebody does get that diagnosis, which can be very scary; what is the typical first line of treatment once it is identified?
  
  Dr. Lotem: It is very important to remember that actually the majority of patients diagnosed with melanoma will be just fine with a simple excision, surgery, simple surgery taking the melanoma out with a safety zone around the melanoma of normal skin and most of the patients with need nothing. I even hesitate to use the word patient. It is people diagnosed with melanoma. It is the minority of people diagnosed with melanoma that eventually develop metastases and the treatment that we would advise can either be prevention treatment we generate in order to reduce the risk that the patient will develop metastases and then we have of course treatment for those unlucky people who did not have early enough diagnosis of the melanoma and eventually developed metastases.
  
  Melanie: So, you are working on some research regarding strengthening the patient’s immune response to a tumor with vaccines. Who is this for? Tell us about this research doctor.
  
  Dr. Lotem: We try to follow the example of infectious disease. If you look to what happened to many deadly infectious diseases that we actually generated a vaccination and thus we induced immune protection and most of the people in society will never have this disease. In the situation of cancer, and especially in the situation of melanoma; this is not simple because melanoma has a lot of similarity with the normal tissues of the body. So, number one what we do right now is generate a vaccine that is made by the patient’s own unique tumor. Today, we know that there is a unique single gene to every individual cancer and it is not just that we can have a general melanoma vaccine, but we need to have the exact features of every patient’s melanoma. This is possible only to patients with advanced melanoma, like metastases to the lymph nodes. The lymph nodes are removed and the patient is fine. There is no sign of disease existing at the time that we offer to receive the vaccine. But we know that these patients are under danger of developing disease which can be as high as 75%. So, one of the scientific efforts that we are doing right now is to deliver a unique individual vaccine to melanoma patients and this probably in the end will not be a sole means of prevention but it will have to be combined with other drug class that is called immune check point modulators and that is very powerful proteins that are given to patients by infusions and these proteins can invigorate, strengthen the killing capacity of immune cells and what we try to do is initially generate immune cells against melanoma and once they have been formed; we strengthen them using the immune check point modulators to have a strong and effective protective immune response.
  
  Melanie: Absolutely fascinating. So, what does current research indicate for future developments and treatments? Give us a little blueprint Dr. Lotem for future research in immunotherapy, targeted therapy, combination therapies. What are you doing?
  
  Dr. Lotem: it is important to know that a lot of the advances in cancer development are actually achieved by the drug companies, by Pharma companies and of course we participate in many clinical trials that are initiated by the leading Pharma companies testing, leading new drugs. Most of them are in the class of immune modulators. These are biologicals that aim to help the immune system be strong enough in order to effectively fight against cancer cells. What is more futuristic and more imaginative is to try and for those patients in whom you cannot induce immune response; to generate for them premade immune cells that are actually you endow with the capacity to kill. So, what you do, is you take a blood sample, by the way, this is research that is done in living centers. It is not yet in our hands in the phase of clinical trials but it is a direction for the future. You take cells from the blood of a patient and during genetic engineering, you give these cells the capacity to recognize cancer in a totally artificial manipulation but you end up with a cell that is a good anticancer killer. This is an effort that we are right now establishing together with the department of bone marrow transplantation and Dr. Polina Stepensky in that department.
  
  What we kindly do before we will be more capable in the genetic engineering is remove metastases for melanoma patients that failed all existing treatments and from these metastases using special growth conditions, we grow and expand immune cells. And in the beginning, those immune cells are very few and very weak. But outside of the body, of the patient, we give them idealized conditions. We incubate them and we can expand them until we receive trillions and trillions of these cells and we infuse them back to the patient. The cells called T to more infiltrate in the lymphocytes and the technique is called adoptive transfer. So, we transfer into the patient immune cells that the few initiating cells will actually take and form the cancer then outside of the body, they will expand that to very large numbers and then now that they are in the huge number, now we give them back and -
  
  Melanie: Wow, are you thinking about extending some of these treatments to patients with colorectal tumors, ovarian malignancies and those of the lung and breast possibly?
  
  Dr. Lotem: So, we know that there are tumors which are more likely to induce effective immune response and there are tumors which are less likely to do so and so the colon – the colorectal cancers tumors that develop on the basis of defects in DNA damage repair. Those tumors are excellent candidates for immunotherapy and yes, we have a vaccine program for colorectal cancer. We have a vaccine program for ovarian cancers. Unfortunately, for breast cancer, at the moment, it is much more difficult to induce immune response and probably the triple negative type of breast cancer will be the first where we will see more and more immune approaches offered to patients.
  
  Melanie: What is your best advice, in summary, Dr. Lotem, for prevention? Is putting on sunscreen enough and is it true that melanoma has become more common since sunscreens were developed?
  
  Dr. Lotem: Well, first it is important to realize that some of our patients develop melanoma totally regardless of sun exposure. Those melanomas are in protected areas and part of the reason for their development is genetics. So, genetics plays a role in melanoma development and sometimes you know it is just fate and we should not blame ourselves for that. Part which is about 50% of the melanomas which develop on the basis of excessive sun exposure, the number one problem is when there is a sunburn. It is very important not to get burned and that sunscreens are protective and are helpful. I do not think that there is a rise in melanoma incidence because of sunscreens and most of the community believes that they are necessary and that is probably is my best advice. Do not burn in the sun.
  
  Melanie: Thank you so much. Dr. Lotem, for being on with us today. This is Hadassah On Call, New Frontiers in Medicine brought to you by Hadassah, the Women’s Zionist Organization of America. The largest Jewish women’s organization in America, Hadassah enhances the health of people worldwide through medical education, care and research innovations at the Hadassah Medical Organization. For more information on the latest advances in medicine please visit Hadassah.org, and to hear more episodes in this podcast series, please visit Hadassah.org/podcasts, that's Haddasah.org/podcasts. I’m Melanie Cole. Thanks so much for listening.
• Hosts: Melanie Cole, MS