Prostate Cancer Lab #51: How Proteomics and RNA Sequencing Are Guiding My Treatment (Mike Yancey)

When cancer treatments work for only a few months, patients, their caregivers, and their medical teams need to continuously identify new treatment options. One of the ways to find new treatments is to pursue cutting edge tests which can identify unique characteristics of a patient’s cancer that can be matched with new options.

Consider the case of Mike Yancey. Mike has an aggressive cancer and runs quickly through treatments. He responds to new treatments, but for an unusually short time, on average a few months. In his search for more treatments, Mike learned about proteomics, a cutting edge analysis of cancer expression, and a proteomics service provider (mProbe), from his participation in the Prostate Cancer Lab. He decided to pursue their test. The proteomic analysis of his tumor identified a new mutation which could be targeted by a chemotherapy which was normally used for lung cancer. It gave him another treatment option.

As Mike’s case shows, patients who are actively engaged in their care are more likely to get better outcomes. They need specific, personalized information about testing and treatment options, which can come from a community of fellow patients and hackathons. They need to find clinicians with whom they can partner to aggressively consider cutting edge tests and treatments.

In this session, Mike reviewed his recent experience and looked for feedback on what he should do next. This is a sequel to a previous session (meeting #27 in September 2022), where Mike described his medical history to that point. (You can see the notes from that session here.) Mike was diagnosed with prostate cancer in July 2021. In May 2022 tests revealed that he had mutations in three key “tumor suppressor genes” (PTEN loss, and RB1 and TP53 mutations). If someone has mutations in any two of these three genes, then the cancer is designated as “Aggressive Variant Prostate Cancer”. In his case, he had mutations in all three, which only 1% of prostate cancer patients have. Patients with this profile do not respond as well to many of the standard prostate cancer drugs. Usually the cancer is held back for up to two years following a treatment, but in his case it was only four months. He also learned that his cancer does not express much prostate specific antigen (PSA).

An Update on Mike’s Story: Successes Quickly Followed by Failures

• Pluvicto Success: In August of 2022 Mike started taking a relatively new drug for the treatment of prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer: “Pluvicto” (Lutetium vipivotide tetraxetan), which latches onto prostate-specific membrane antigen (PSMA) and delivers targeted radiation. Things initially seemed to be going quite well. Then around October he had a lesion show up on his spine, and they determined that it was not producing PSMA, so the Pluvicto was not working on that particular lesion. Mike had radiation on that lesion, hoping that would take care of it. The oncologist said that if it wasn’t for this non-PSMA-producing cancer on his spine, he would be a “poster boy” for a successful Pluvicto treatment.
• Pluvicto Failure: In late December Mike ended up in the hospital due to severe pain in his right hip and right shoulder. The pain was so severe that he was unable to stand unassisted. He had additional aggressive spine lesions growing on his spine, and they were pressing on his spinal cord. Once again, the cancer in his spine was not producing PSMA. Therefore, Pluvicto was not going to touch it and was not going to be of any benefit. He needed to stop Pluvicto since adding another drug would have high toxicity. He stopped Pluvicto after his fourth treatment in mid-December.
• Next Treatment Identification: An October biopsy of Mike’s spine lesion had been sent to a proteomics diagnostic firm (mProbe), and they reported no androgen receptor expression, which meant that his cancer would not respond to drugs that attack androgen. Mike needed to find other treatment options quickly. mProbe further reported that Mike had high levels of a protein (“TOP2A”), for which there was a chemotherapy drug (Etoposide), a chemotherapy usually used for lung cancer, as opposed to the typical chemotherapy combination for prostate cancer (Cabazitaxel and Carboplatin). His oncologist also wanted to include Carboplatin, so he started taking Etoposide and Carboplatin in January 2023.
• A Qualified Success: The chemotherapy worked quite well, except for the cancer on his hip, pelvis, and femur (the PSMA-producing cancer). The lesions on his spine were not growing, and at this point, no additional lesions had been identified. But the question remained: why was the cancer on his hip, pelvis, and femur growing?
• Flare up: In January Mike’s hip pain increased, so in January and February he had radiation on it, which relieved the pain during those two months, allowing him to be mobile.
• More Trouble: On March 5 Mike’s right hip and pelvis pain began again, and on March 6 scans showed renewed cancer growth from the PSMA-expressing cancer in his pelvis, hip, and femur, and he had his first PSA increase in four months. During January and February his PSA had continued to decrease to a low point of 0.14, but on March 6 his PSA jumped to 0.37, and his testosterone rose from non-detectable in January to 28 in February and 128 in March. The PSA increase was probably due to an experiment Mike had run to see what would happen if he stopped androgen deprivation therapy, which he had done in December, with the agreement of his oncologist. Normally an oncologist would not stop ADT just to see what happens, but Mike wanted to see if his testosterone increased whether it would cause his cancer to begin growing. It took three months for the testosterone to begin to rise. So it was pretty obvious that a lot of the reason for the renewed pain around March 5 was due to the cancer growing because it now had lots of testosterone to feed off of.
• Treatment Restart: Mike restarted ADT on March 6, using the oral drug Orgovyx. Mike had to stop taking a heartburn drug which interacts with Orgovyx since it slowed the Orgovyx effect.

What’s up next for Mike?

Mike has many treatment options in his portfolio. He received an RNA seq interpretation from SHEPHERD Bio that identified ten potential drugs plus one multi-drug combination, which he needs to review with his oncologist. He also has a 3-drug combination option that he got from CureMatch. Mike has plans for a bone biopsy on his right hip on April 18 that will enable more testing, including another proteomics analysis by mProbe, another RNA sequencing analysis by Tempus, RNA seq interpretation by SHEPHERD Bio, and possibly sequencing and analysis by Foundation Medicine.