Podcast Summary
A promising new direction in cancer research: Dr. Malkas is developing a cancer treatment that can remove tumors while leaving healthy cells intact, potentially improving cancer treatments and saving lives
Cancer is a complex and evolving entity that is difficult to treat due to its ability to mimic healthy cells and constantly change. However, a promising new direction in cancer research comes from Dr. Linda Malkas at City of Hope Cancer Research and Treatment Center, who is following the science to develop a treatment that can remove cancerous tumors while leaving healthy cells intact. This approach, if successful, could significantly improve cancer treatments and save lives. Dr. Malkas, an associate chair and professor in molecular and cellular biology, emphasized that cancer is not just a collection of cells, but a living entity that evolves and uses our own body's processes against us. Despite the challenges, she remains optimistic about the potential for new treatments and congratulated everyone for being cancer survivors.
The Immune System Fights Against Cancer Cells: Cancer cells evade the immune system by damaging their own DNA, allowing them to survive and thrive. Our bodies produce and eliminate cells, including cancer cells, due to the vast amount of genetic information we carry.
Our bodies constantly produce cancer cells, but our immune systems work to eliminate them. However, cancer cells have the ability to evade this surveillance system by continually damaging their own DNA and changing themselves. This process, called constitutive replication stress, allows cancer cells to survive and thrive. The human body contains an immense amount of DNA, with 3 feet of it in every cell, and if all of it were stretched out, it would reach beyond the sun. Despite this, removing all DNA from a human would result in death. These ancient machines that we are, harbor a vast amount of genetic information, and the constant production and elimination of cells, including cancer cells, is a testament to the complex and miraculous nature of life.
Differences in PCNA in cancer cells lead to new targets for cancer treatment: Understanding PCNA's role in cancer cells can lead to selective inhibition of cancer growth through targeted drug development
The protein Proliferating Cell Nuclear Antigen (PCNA), which functions as a sliding clamp protein during DNA replication, is different in cancer cells compared to normal cells. This difference in PCNA leads to altered DNA replication and the development of new molecular targets for potential cancer treatments. The interaction of PCNA with over 200 other proteins in the human cell makes it an attractive target for drug development, as a drug designed to target the cancer cell-specific form of PCNA could potentially selectively inhibit cancer cell growth without affecting normal cells. This discovery highlights the importance of understanding the molecular mechanisms of cancer and the potential for developing targeted therapies.
Discovering an 'undruggable' cancer target: Dr. Malcus' determination and persistence led to the discovery of AOH 1996, a non-enzyme protein target for cancer treatment, despite initial skepticism from the scientific community.
The discovery of AOH 1996, a molecular target for cancer treatment, was a groundbreaking achievement due to its ability to selectively target and kill cancer cells by disrupting an entire network of 200 protein functions within the cancer cell, while leaving healthy cells unharmed. However, the path to this discovery was not easy. The scientific community held certain dogmas, such as the belief that only enzymes could be targeted with drugs. When Dr. Malcus presented her discovery to a large pharmaceutical company, they dismissed it as "undruggable" due to its involvement in protein-protein interactions and its non-enzyme nature. Undeterred, Dr. Malcus made a promise to a family affected by cancer and dedicated herself to finding a solution. Despite initial setbacks, her determination and persistence led to the development of a drug that could effectively target and kill cancer cells while sparing healthy cells. While the motivation for her work may have been fueled by a desire to prove doubters wrong, the long-term impact of her discovery lies in its potential to revolutionize cancer treatment and save countless lives.
Targeting PCNA as a hub in cancer research: Unique perspective and collaboration led to identifying a specific domain on PCNA, which led to the development of a successful cancer treatment through virtual screening of 6 million molecules.
The speaker's groundbreaking approach to cancer research involved targeting the PCNA protein not as an enzyme, but as a hub or terminal in the cell's replication process. This thinking was different from traditional research methods and led her to City of Hope, where she was able to collaborate with a team and identify a specific domain on the PCNA molecule that differed between cancer and normal cells. With this information, they screened over 6 million molecules using virtual screening technology to find those that fit into the identified pocket, ultimately leading to the development of a successful cancer treatment. This innovative approach, inspired by the idea of shutting down a system from within, demonstrates the importance of unique perspectives and collaborative efforts in scientific research.
Using computer simulations to identify new cancer drugs: Researchers identified 53 promising compounds for cancer treatment by analyzing 6.5 million molecules using advanced technology. Five of these compounds selectively kill cancer cells and spare normal cells.
Advanced technology, such as computer simulations, can help identify potential new drugs for cancer treatment. In this specific case, researchers used a protein structure and a computer to analyze 6.5 million molecules, resulting in the identification of 53 promising compounds. Five of these compounds were found to selectively kill cancer cells and leave normal cells unharmed. This discovery went through various stages of testing, including animal trials, and is now in a phase one clinical trial for humans. Cancer is viewed as a molecular signature disease, meaning it's not a single disease but a collection of various diseases with unique molecular features. This discovery demonstrates the importance of personalized medicine and the potential for developing targeted treatments for different types of cancer.
Understanding cancer as a unique condition for each individual: Precision medicine focuses on a patient's unique tumor molecular signature to tailor treatments, considering both the tumor and its environment.
Cancer is no longer seen as a one-size-fits-all disease, but rather as a unique condition tailored to each individual. The molecular signature of a tumor, which is unique to that person, is a major focus in the field of precision medicine. This approach considers not only the tumor itself but also the environment around it, which can influence cancer activity. Cancer is likened to a parasite that thrives by adapting to its host. With the help of genome sequencing, doctors can identify drugs that may be effective for a patient based on their tumor's molecular signature, even if the drug was initially designed for a different type of cancer. This is a revolutionary shift in thinking and practice, moving away from a myopic focus on the tumor alone. Immunotherapy is a promising area of research in cancer treatment, where the body's own immune system is harnessed to fight cancer cells. However, more research is needed to understand how the body naturally eliminates cancer cells and replicate that process effectively.
Improving cancer treatment through precision medicine and immune system therapy: Immunotherapy, like AOH 1996, uses the immune system to control cancer growth and is given as a pill. Researchers aim to make cancer manageable through refined and combined treatments.
Cancer treatment is evolving from a critical disease to a managed one, thanks to advancements in precision medicine and immune system therapy. Immunotherapy, such as AOH 1996, harnesses the power of the immune system to keep cancer in check. It's given as a pill with a short half-life, requiring twice-daily doses to maintain its presence in the body. This approach aims to make treatment more convenient for patients, while also accounting for cancer's ability to adapt and evolve. The ultimate goal is to turn cancer into a manageable condition, allowing people to live longer, healthier lives. However, it's important to remember that cancer is constantly adapting, so a single therapy won't be enough. Instead, researchers are working on refining and combining various treatments to create a more effective arsenal against cancer.
Half-life and drug effectiveness: Properly understanding half-life is essential for effective medication use, especially with antibiotics and cancer treatments. Combination therapies, using multiple drugs together, offer improved effectiveness and reduced toxicity.
Understanding the concept of half-life is crucial when taking medications, including antibiotics. This term should be clearly labeled on drug bottles to emphasize its importance. Half-life refers to the time it takes for the concentration of a drug in the body to reduce by half. Neglecting proper dosage schedules can lead to ineffective treatment or even drug resistance. In the context of cancer treatment, monotherapy, or a single drug treatment, is becoming less popular as researchers shift towards combination therapies, or "cocktails," to improve effectiveness and reduce toxicity. These combination therapies involve using multiple drugs together to target various aspects of cancer growth. Platinum compounds, which attack DNA, are an example of chemotherapeutics that can be toxic due to their indiscriminate targeting of proliferating cells. Combination therapies, such as AOH 1996, hold promise for more effective cancer treatments while minimizing side effects.
A new approach to cancer treatment targets hubs in cells instead of single enzymes: The hubba hubba hypothesis proposes targeting cell hubs for more effective cancer treatments, potentially leading to fewer toxic doses and greater success in the next decade.
The development of a new drug, AOH 1996, shows promise in complementing currently used drugs and reducing the need for toxic doses, allowing for effective tumor growth inhibition without harming the animal. However, the issue of cancer cell resistance to drugs, especially kinase inhibitors, remains a challenge. The cancer cells adapt and change, much like billions of cells in nature, to survive. This is why the speaker proposes a new approach, "hubba hubba hypothesis," which targets hubs or control centers in the cell, such as PCNA, to shut down entire networks instead of focusing on single enzymes. In the next decade, this approach could lead to more effective cancer treatments by targeting entire systems rather than individual stars. The last 10 years have seen remarkable progress in cancer therapy, and the next 5 to 10 years could bring even more groundbreaking discoveries.
Personalized medicine in cancer treatment: The future of cancer treatment involves identifying unique molecular signatures of each tumor and matching them with the most effective treatments, increasing chances of a cure and effective treatment during remission.
The future of cancer treatment lies in personalized medicine, where the unique molecular signature of each tumor is identified and matched with the most effective treatment. This approach is like getting a bespoke suit instead of an off-the-peg one, as it is tailored specifically for the individual's tumor. With this method, doctors can accurately predict which drugs will be most effective for each patient, increasing the chances of a cure and effective treatment during remission. This is a significant departure from the outdated notion of finding one cancer gene or drug that would work for everyone. The use of molecular signatures to identify each tumor's unique address is revolutionizing cancer treatment and giving patients a fighting chance against this disease.